INTRODUCTION — Colorectal cancer (cancer of the large portion of the bowel [colon] or rectum) is a common, preventable disease. Approximately one-third of people who develop it die of the disease, making it the second leading cause of cancer death. However, screening tests now make it possible to detect existing cancers at an early, treatable stage and even to prevent the development of colorectal cancer.
There is general agreement by experts that all adults should undergo screening beginning at age 50, or earlier for people who are at high risk for colorectal cancer. Several different tests are currently available, and new tests are being developed; all of these have advantages and disadvantages. The optimal screening test depends upon a person's preferences and their risk of colon cancer. It is important to review each test's effectiveness, safety, convenience, and costs.
EFFECTIVENESS OF SCREENING — Most colorectal cancers develop gradually over many years. They begin as small, benign tumors called adenomatous polyps. These polyps grow, develop precancerous changes, eventually become cancerous, and later spread and become incurable. This progression takes at least 10 years in most people.
The screening tests described below all work by detecting pre-cancers at the polyp stage before they become cancerous or by detecting cancers themselves while they are still curable. Regular screening for and removal of polyps can reduce a person's risk of developing colorectal cancer by up to 90 percent. In addition, early detection of cancers that are already present in the colon often allows for successful treatment.
WHO SHOULD BE SCREENED? — Several factors increase an individual's risk of developing colorectal cancer. The presence of these factors will determine the age at which screening should begin, the frequency of screening, and the screening tests that are most appropriate.
Small increases in risk — Several characteristics increase the risk of colorectal cancer two to several fold. While each is of some importance individually, risk can be substantially increased if several are present together. Family history of colorectal cancer — The occurrence of colorectal cancer in a family member increases the risk of getting the cancer, especially if it is a first degree relative (a parent, brother or sister, or child), several family members are affected, or if the cancers have occurred at an early age (eg, before age 55 years). Prior colorectal cancer or polyps — People who have previously had colorectal cancer have an increased risk of developing a new colorectal cancer. People who have had adenomatous polyps before the age of 60 years are also at increased risk for colorectal cancer. (See "Patient information: Colon polyps"). Increasing age — Although the average person has a 5 percent lifetime risk of developing colorectal cancer, 90 percent of these cancers occur in people older than 50 years of age. Risk increases throughout life. Race — Black Americans have a higher risk of dying from colorectal cancer than white Americans. This risk is also high in native Alaskans and low in American Indians. Lifestyle factors — Several lifestyle factors have been linked to the risk of colorectal cancer. Factors that appear to increase risk include: A diet high in fat and red meat and low in fiber A sedentary lifestyle Cigarette smoking
Factors that may decrease risk include: Folic acid supplements Calcium supplements Aspirin, ibuprofen, and related drugs (the evidence for these is not yet strong enough to recommend taking them for this purpose)
Large increase in risk — Some conditions are associated with very high rates of colorectal cancer. Familial adenomatous polyposis — Familial adenomatous polyposis (FAP) is an uncommon inherited condition associated with an increased risk of colorectal cancer. Nearly 100 percent of people with this condition will develop colorectal cancer during their lifetime, and most of these cancers occur before the age of 50 years. FAP causes hundreds of polyps to develop throughout the colon. Hereditary nonpolyposis colon cancer — Hereditary nonpolyposis colon cancer (HNPCC) is another inherited condition associated with an increased risk of colorectal cancer. It is slightly more common than FAP, but is still uncommon. About 70 percent of people with HNPCC will experience colorectal cancer by the age of 65. Cancer also tends to occur at younger ages and in the part of the colon on the right side of the body (the ascending colon).
HNPCC is suspected in those with a strong family history of colon cancer; several family members from different generations may have been affected, some of whom developed the cancer relatively early in life. Persons with HNPCC are also at risk for other types of cancer, including endometrial (uterine), stomach, bladder, renal (kidney) and ovarian cancer. Inflammatory bowel disease — The risk of colorectal cancer is increased in people with Crohn's disease of the colon or ulcerative colitis. The risk increases as the amount of inflamed colon increases and as the duration of disease increases; pancolitis (inflammation of the entire colon) and colitis of 10 years' duration or longer are associated with the greatest risk for colorectal cancer. Risk is not increased in irritable bowel disease.
SCREENING TESTS — Four tests are currently recommended for colorectal cancer screening: the fecal occult blood test, sigmoidoscopy, barium enema, and colonoscopy.
Fecal occult blood test — Colorectal cancers (and, more rarely, polyps) often bleed, releasing microscopic amounts of blood into the stool. The blood is frequently not visible to the naked eye, requiring specialized tests for detection. The fecal occult blood test can be used to detect blood in the stool. Procedure — This simple test is performed by putting small amounts of stool on chemically coated cards. Usually, two samples from three consecutive stools are applied to the cards at home and returned to the clinician. The sample on the card is then treated with a solution that changes color when blood is present.
Some simple dietary restrictions for two days prior to testing can improve the accuracy of the test. These include: Eliminate red meat, turnips, and horseradishes Avoid drugs that may irritate the stomach lining (such as aspirin, ibuprofen-like drugs) Do not take vitamin C Eat high-fiber foods Effectiveness — The fecal occult blood test, when performed once every year, has been shown to reduce the risk of dying from colorectal cancer by up to one-third [1]. Risks and disadvantages — Because polyps seldom bleed, the fecal occult blood test is less likely to detect polyps than other screening tests (see below). In addition, only 2 to 5 percent of people with a positive test actually have colorectal cancer; thus, for every patient with cancer, 50 patients are unnecessarily distressed and undergo tests that eventually reveal no cancer. Following the dietary restrictions above reduces the chance of a false-positive test. Additional testing — If a fecal occult blood test has a positive result, the entire colon should be examined, usually with colonoscopy.
Sigmoidoscopy — Sigmoidoscopy allows direct viewing of the lining of the rectum and the lower part of the colon (the descending colon, show figure 1). This area accounts for about one-half of the total area of the rectum and colon, where half of the cancers occur. (See "Patient information: Flexible sigmoidoscopy"). Procedure — Sigmoidoscopy requires that the patient prepare by cleaning out the bowel. This usually involves consuming a clear liquid diet, laxatives, and using an enema shortly before the examination. During the procedure, a thin, lighted tube is advanced into the rectum and the left side of the colon to check for polyps and cancer. Biopsies (small samples of tissue) can be removed during sigmoidoscopy. Sigmoidoscopy may be performed in a doctor's office. The procedure may cause mild cramping; most people do not need sedative drugs and are able to return to work or other activities the same day. Effectiveness — Physicians who perform sigmoidoscopy can identify polyps and cancers in the descending colon and rectum with a high degree of accuracy. Studies suggest that sigmoidoscopy, performed as infrequently as every 5 to 10 years, reduces death from cancers in the lower half of the colon and rectum (the area directly examined) by 66 percent [2]. Risks and disadvantages — The risks of sigmoidoscopy are small. The procedure can create a small tear in the intestinal wall in about 2 per every 10,000 people; death from this complication is rare. A major disadvantage of sigmoidoscopy is that it cannot detect polyps or cancers located in the right side of the colon. Additional testing — Certain changes in the left-sided colon increase the likelihood of polyps or cancer in the remaining part of the colon. Thus, if sigmoidoscopy reveals suspicious findings in the left-sided colon, such as many small polyps or polyps with certain microscopic features, colonoscopy may be recommended to view the entire length of the colon.
Fecal occult blood test and sigmoidoscopy — Combined screening with a fecal occult blood test and sigmoidoscopy is a common practice and may be more effective than screening with either test alone [3].
Colonoscopy — Colonoscopy allows direct viewing of the lining of the rectum and the entire colon (show figure 1). (See "Patient information: Colonoscopy"). Procedure — During colonoscopy, a thin, lighted tube is used to directly view the lining of the rectum and the entire colon. This test can therefore detect polyps and cancers that are beyond the reach of the sigmoidoscope. People are usually given a mild sedative drug during the procedure. Effectiveness — Colonoscopy detects most small polyps and almost all large polyps and cancers [4]. Polyps and some cancers can be removed during this procedure. Risks and disadvantages — The risks of colonoscopy are greater than those of other screening tests. Colonoscopy leads to serious bleeding or a tear of the intestinal wall in about 1 in 1,000 people. Because the procedure requires sedation, most people must be accompanied home after the procedure and are unable to return to work or other activities on the same day.
Barium enema test — A barium enema test provides a detailed x-ray picture of the rectum and the entire colon (show figure 1). A double-contrast barium enema is usually recommended. Procedure — During a barium enema test, liquid barium is used to coat the inside of the colon. The barium outlines the profile of the colon on x-rays and can reveal structural abnormalities such as polyps and cancers. Preparation for a barium enema entails cleansing the colon with a saline laxative. Some people experience mild cramping during the procedure, but sedative drugs are usually not necessary, and most people can return to work or other activities on the same day. Effectiveness — The barium enema test detects about one-half of large polyps and about 40 percent of all polyps in the colon and rectum [5]. Most experts feel that screening with barium enema reduces the risk of dying from colorectal cancer, but this has not been definitively proven. Risks and disadvantages — The barium enema test is relatively safe compared with other screening tests for colorectal cancer. Additional testing — If a barium enema test reveals an abnormality, a colonoscopy may be recommended.
New tests — Several new screening tests for colorectal cancer are being developed and evaluated. These tests include improved fecal occult blood tests, fecal tests for genetic abnormalities linked to colorectal cancer, and a type of computed tomography (CT) scan called a virtual colonoscopy. These tests are still being studied, and they are not yet recommended for routine screening.
Virtual colonoscopy, in particular, is being performed more commonly. The major advantages of virtual colonoscopy compared with optical colonoscopy are that the procedure is safe, and there is no need for sedation. However, if a worrisome polyp is found on virtual colonoscopy, a traditional colonoscopy will be needed for confirmation and biopsy. Additionally, the accuracy of virtual colonoscopy depends upon how it is performed; the test that is currently available may not be accurate enough for use as a screening test.
SCREENING PLANS — The screening plan that is recommended depends upon a person's risk of colorectal cancer.
Average risk of colorectal cancer — People with an average risk of colorectal cancer should begin screening at age 50. The tests differ in features (effectiveness in preventing cancer, comfort, safety, cost, and convenience). No single screening test has been identified as the best test. The available options should be discussed with a clinician to develop a screening plan that can be followed.
Some clinicians recommend a fecal occult blood test once per year and a sigmoidoscopy once every five years; a combination of these screening tests may also be recommended. Alternative screening plans include a barium enema test once every five years or colonoscopy once every 10 years. If the results of one or more of these tests is abnormal, more frequent examinations with colonoscopy may be recommended.
Increased risk of colorectal cancer — Screening plans for people with an increased risk may entail screening at a younger age, more frequent screening, and the use of more sensitive screening tests (like colonoscopy). The optimal screening plan depends upon the reason for increased risk.
Family history of colorectal cancer
- People who have one first-degree relative (parent, brother, sister, or child) who has experienced colorectal cancer or adenomatous polyps at a young age (before the age of 60 years), or two first-degree relatives diagnosed at any age, should begin screening earlier, typically at age 40, or 10 years younger than the earliest diagnosis in their family, whichever comes first, and screening should be repeated every five years.
- People who have one first-degree relative (parent, brother, sister, or child) who has experienced colorectal cancer or adenomatous polyps at age 60 or later, or two or more second degree relatives (grandparent, aunt, uncle) with colorectal cancer should begin screening at age 40, and screening should be repeated as for average risk people.
- People with a second-degree relative (grandparent, aunt, or uncle) or third-degree relative (great-grandparent or cousin) with colorectal cancer are considered to have an average risk of colorectal cancer (See "Average risk of colorectal cancer" above).
Familial adenomatous polyposis — People with a family history of familial adenomatous polyposis (FAP) should consider genetic counseling and genetic testing to determine if they carry the affected gene. People who carry the gene or do not know if they carry the gene should begin screening with sigmoidoscopy once every year, beginning at puberty. If this screening reveals many polyps, plans for colectomy (surgical removal of the colon) should be considered; this surgery is the only way to prevent colorectal cancer in people with FAP.
Hereditary nonpolyposis colon cancer — People with a family history of hereditary nonpolyposis colon cancer (HNPCC) should consider genetic counseling and genetic testing to determine if they carry the affected gene. People who carry the gene or who do not know if they carry the gene should be screened with colonoscopy or barium enema because HNPCC is associated with cancers of the right-sided colon. This screening should be done once every one to two years between age 20 and 30 years, and once every year after age 40. Because polyps can progress more rapidly to cancer in people with HNPCC, more frequent screening may also be recommended.
Inflammatory bowel disease — In people with ulcerative colitis or Crohn's disease of the colon, the optimal screening plan depends upon the amount of colon affected and the duration of the disease. Screening usually entails colonoscopy once every one to two years beginning after eight years of pancolitis (inflammation of the entire colon) or after 15 years of colitis of the left-sided colon. (See "Patient information: Crohn's disease" and see "Patient information: Ulcerative colitis").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The American Gastroenterological Association
(www.gastro.org)
The American College of Gastroenterology
(www.acg.gi.org)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Mandel, JS, Bond, JH, Church, TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993; 328:1365.
2. Selby, JV, Friedman, GD, Quesenberry, CP Jr, Weiss, NS. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992; 326:653.
3. Winawer, SJ, Flehinger, BJ, Schottenfeld, D, Miller, DG. Screening for colorectal cancer with fecal occult blood testing and sigmoidoscopy. J Natl Cancer Inst 1993; 85:1311.
4. Rex, DK, Cutler, CS, Lemmel, GT, et al. Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Gastroenterology 1997; 112:24.
5. Winawer, SJ, Stewart, ET, Zauber, AG, et al. A comparison of colonoscopy and double-contrast barium enema for surveillance after polypectomy. National Polyp Study Work Group. N Engl J Med 2000; 342:1766.
Friday, October 12, 2007
Screening for cervical cancer
INTRODUCTION — The Pap smear is a common test used to screen women for cervical precancer or cancer. However, most abnormal Pap smears are not due to cancer, but rather caused by infection or low estrogen levels.
This topic reviews the anatomy of the cervix, factors that increase a woman's risk of having cervical precancer or cancer, tests to detect cervical abnormalities, and a description of both normal and abnormal Pap smear results. A separate topic is available that discusses treatment of abnormal Pap smears. (See "Patient information: Treatment of abnormal Pap smears").
ANATOMY OF THE CERVIX — The cervix is located at the lower end of the uterus (show figure 1). The surface of the cervix includes several layers of cells. Squamous cells make up the outer layer of the cervix and vagina.
The cervix also includes glandular (also called columnar) cells, which line the opening in the cervix. The region where the two cell types meet is called the "transformation" zone (show picture 1). The transformation zone is the region most likely to contain abnormal cells.
If more than one third of the layers contain abnormal cells, this is called high grade squamous intraepithelial lesion (HSIL or HGSIL) (show figure 2).
What is a Pap smear? — A Pap smear is a method of examining cells from the cervix. The traditional Pap smear (named after Dr. Papanicolaou) involved smearing the cervical cells onto a glass slide. More recently, liquid-based tests (eg, ThinPrep, SurePath) have become available; these tests place the sample of cervical cells into a vial containing a liquid preservative. In both types of test, the cells are viewed with a microscope to detect abnormalities.
Cervical cells may appear abnormal for a variety of reasons. For example, a woman may have low estrogen levels or a cervical infection, or she may have a precancerous area or even cervical cancer. If the Pap smear is abnormal, further testing is needed to determine what the abnormality is and if treatment is needed.
Who should have a Pap smear? — The first Pap smear should be done by age 21 years. For most women, a Pap smear is recommended every one to three years. For women who have a past history of abnormal Pap smears or who have risk factors for cervical cancer, testing is recommended once per year (see "Risk factors for cervical cancer" below).
Women who are older than 30 years who have no risk factors, a negative Pap smear three years in a row, and a negative HPV test may choose to have a Pap smear and HPV testing every three years rather than every year (see "HPV testing" below). Most experts feel that women who are at low risk for cervical cancer (eg, no past history of an abnormal Pap) can discontinue Pap smears by age 65 to 70 years.
How are Pap smears obtained? — Pap smears are performed during a pelvic examination. To perform the test, a healthcare provider uses an instrument (speculum) to view the cervix, which is located at the lower end of the uterus (show figure 1). The provider sweeps the surface of the cervix and inner cervix (called the endocervical canal) with a soft brush or small spatula to collect cervical cells. This is not painful.
Pap smear accuracy — Most Pap smears can accurately identify women with abnormal cervical cells. However, the test is not perfect, and it misses between 5 and 25 percent of women with abnormalities. These women are said to have a false negative result. There are several important points to consider when discussing false negative results: Many false negative results are due to difficulty in collecting a sufficient number of cervical cells, not errors in reading the smear. It may be difficult to collect cervical cells if the cervix is hard to find during a pelvic examination, if the abnormal area is very small or high up inside the cervix, if only a few cervical cells are obtained, if the specimen dries too quickly, if the patient douches or has sexual intercourse before the examination, or if the woman is bleeding or has an infection at the time of the Pap smear. If a woman has a normal result three years in a row, then it is unlikely that an abnormality has been missed. The frequency of screening for cervical cancer can then be spread out (see "Who should have a Pap smear?" above). If a new lesion develops in a woman who is only tested every three years, it will be found before it becomes serious because it takes years for a new abnormality to develop into a high-grade precancer or cervical cancer. It usually takes many years for precancerous cervical cells to progress to cancer, and progression to cancer does not always occur.
RISK FACTORS FOR CERVICAL CANCER — The most important risk factor for cervical cancer is infection with the human papillomavirus (HPV). Other factors that increase the risk of cervical cancer include sexual intercourse, use of tobacco (eg, cigarettes), use of birth control pills, and a weakened immune system (eg, due to HIV infection or certain medications) (show table 1).
Human papillomavirus — Infection of the cervix with certain types of human papillomavirus (HPV) is the most significant risk factor for cervical abnormalities and cancer. Over 100 different types of HPV have been identified, however not all types infect the cervix or cause cancer. Researchers have labeled the HPV types as being high or low risk for causing cervical cancer. HPV types 6 and 11 can cause warts and are low-risk types because they rarely cause cervical cancer; types 16 and 18 are considered high-risk types because they may cause cervical cancer in some women. (See "Patient information: Condyloma (genital warts) in women").
HPV is spread by direct skin-to-skin contact, including sexual intercourse, oral sex, anal sex, or any other contact involving the genital area (eg, hand to genital contact). It is not possible to become infected with HPV by touching an object, such as a toilet seat.
Most persons who are infected with HPV have no signs or symptoms. Most HPV infections are temporary and resolve within two years. When the virus persists (in 10 to 20 percent of cases), there is a higher likelihood of developing cervical cell abnormalities and cancer. However, it usually takes several years for HPV infection to cause cervical cancer (see "HPV testing" below).
Sexual history — Cervical cancer is rare in women who have never had sexual intercourse. Cervical cancer is more common in women who have had more than one sexual partner or whose partners have more than one sexual partner. Other risk factors include: HIV infection, sexual intercourse before age 17, or a history of sexually transmitted diseases (eg, genital herpes or Chlamydia).
Tobacco use — Smoking cigarettes increases the risk of cervical cancer and precancer by up to seven times that of women who do not smoke. This is believed to occur because cancer-causing products from tobacco are secreted into the cervical mucous. Stopping smoking can decrease this risk. (See "Patient information: Smoking cessation").
Birth control with estrogen — Woman who use a birth control method that contain estrogen (eg, pills, patch) have a slightly higher risk of cervical precancers and cancers compared to women who do not take them (show table 1). The risk of cervical cancer related to birth control is small, and is related to infection with HPV. Thus, women who take a birth control with estrogen but are not infected with HPV have no increased risk of cervical cancer or precancer.
The reason that oral contraceptives increase the risk of cervical cancer is not clear. Higher levels of estrogen may causes changes in the cervix that increase the growth of cells that develop as a result of the HPV infection.
However, birth control with estrogen has a number of benefits, including a reduced risk of ovarian and uterine cancer and decreased pain and bleeding with menstrual periods. Women should discuss all the risks and benefits of this type of birth control with a healthcare provider. (See "Patient information: Hormonal methods of birth control").
Weakened immune system — Normally, the immune system works to protect the body from illness and infection, including the infection caused by human papillomavirus. Women with a weakened immune system have a significantly increased risk of cancers and precancers of the cervix.
A number of factors can weaken the immune system, including HIV infection, prolonged use of glucocorticoids (eg, prednisone), and use of medications to prevent rejection after organ transplantation.
PAP SMEAR RESULTS — The information reported in a Pap smear is described in table 2 (show table 2A-B). Pap smear results may be reported as:
Negative — Pap smears that have no abnormal, precancerous, or cancerous cells are labeled as "Negative for intraepithelial lesion or malignancy".
Smears that are negative can show other conditions, such as a vaginal infection (Trichomoniasis, yeast, herpes, or bacterial vaginosis) or cellular changes related to vaginal dryness, radiation therapy, or an intrauterine device (IUD) string. In some situations, further testing and/or treatment are needed.
Abnormal results — A number of medical terms are used to describe abnormalities of the cervix, including dysplasia, squamous intraepithelial lesion, and intraepithelial neoplasia. These terms all mean that the abnormality is confined to the surface or glandular lining of the cervix.
Follow up testing — Further testing is often needed after an abnormal Pap smear. The most common tests include HPV testing and colposcopy.
HPV testing — HPV testing is recommended only in particular circumstances: If the Pap smear shows a specific abnormality (for example, atypical squamous cells of uncertain significance, or ASC-US), HPV testing is then performed. This is called reflex testing.
Testing every woman for HPV is not recommended because of the risk of false positive results (when the HPV test was falsely positive and the Pap smear was negative). It is likely that many women develop HPV infections that resolve spontaneously. Having a false positive result would lead to unnecessary follow-up testing and anxiety for many women.
Colposcopy — Colposcopy is an office procedure that allows a clinician to closely examine the cervix. It is commonly performed after an abnormal Pap smear. Colposcopy is performed similar to a pelvic examination, while the woman lies on an exam table. A speculum is used to view the cervix, and the viewing device (called a colposcope) remains outside the woman's body (show picture 2).
The colposcope magnifies the appearance of the cervix 10 times. This allows the clinician to better see the location and size of any abnormalities, and also to see any changes in the capillaries (small blood vessels) on the surface of the cervix. Capillary changes are not detected by cervical cytology or HPV tests, but are important signs of the severity of cervical abnormalities.
Using the colposcope, a small piece of the abnormal area can be removed (biopsied). Anesthesia (numbing medicine) is not needed because the biopsy causes only mild discomfort or cramping. The biopsy is then examined with a microscope by a physician (called a pathologist). The results of the biopsy are usually available within one to two weeks.
Some women also need to have a biopsy of the inner cervix during colposcopy; this is called endocervical curettage. Endocervix refers to the inner cervix and curettage means scraping.
ATYPICAL SQUAMOUS CELLS (ASC) — A Pap smear may be read as atypical when cervical cells are not completely normal but are not thought to be precancerous. Further testing of ASC is suggested because some women (5 to 17 percent) have a precancerous lesion that is seen when colposcopy is performed. ASC is subdivided into ASC-US and ASC-H; ASC-H is more likely than ASC-US to be caused by a precancerous change.
ASC-US — There are three options for follow up of a single ASC-US result: Perform HPV testing. This is the preferred follow up for ASC-US. HPV testing can often be done at the same time as the Pap smear. This is convenient because a woman does not have to return for a second visit (see "HPV testing" above).
Women who test positive for high-risk HPV types are referred for colposcopy because they are at greater risk of having a precancerous lesion.
Women who test negative for HPV are not likely to have cervical precancer. These women should have a repeat Pap smear in one year. In most cases, the ASC-US resolves on its own. Repeat the Pap smear in four to six months. If this Pap is normal, it is repeated every four to six months until there have been two normal tests in a row. If the woman has two ASC-US results, she should have colposcopy.
For postmenopausal women, use of an estrogen treatment in the vagina for one month may be recommended after one ASC-US result; low estrogen levels in the vaginal and cervical tissues can cause mild cellular abnormalities that often revert to normal after estrogen treatment. Colposcopy should be performed if the woman has a second ASC-US result after use of estrogen therapy. Have colposcopy. This approach is preferred for women who are HIV positive or who have a weakened immune system because of the higher risk of a precancerous lesion (see "Colposcopy" above).
ASC-H — This finding requires further testing with colposcopy (see "Colposcopy" above).
LOW-GRADE SQUAMOUS LESION (LSIL) — These are mild cellular changes. Further testing is almost always recommended for women with LSIL because 15 percent of women with LSIL have a precancerous lesion that was not detected by the Pap smear.
A small number of women with low-grade changes will develop cancer over a period of several years if no treatment is performed. A large percentage (50 to 90 percent) of women with low-grade changes do not require treatment because the abnormality resolves on its own.
Low-grade abnormalities may be described with other names, including low-grade squamous intraepithelial lesions (LSIL), cervical intraepithelial neoplasia, grade 1 (CIN 1), and mild dysplasia.
Follow up of LSIL — Colposcopy is recommended for women with low-grade lesions (LSIL) (see "Colposcopy" above). Determining the size and location of the lesion with colposcopy can help to decide whether to treat the lesion or follow it over time. Large lesions are less likely to heal without treatment. Observing the extent and severity of the lesion with colposcopy is useful for establishing a baseline in women who are not treated.
However, LSIL in postmenopausal or adolescent women may be approached differently. A repeat Pap smear or HPV test may be recommended for adolescents; if the HPV is positive or the Pap smear continues to be abnormal, the adolescent is usually referred for colposcopy. Postmenopausal women may be treated with a course of estrogen cream, as described above (see "Atypical squamous cells (ASC)" above).
Treatment of LSIL — There are three options for management of LSIL: Close follow-up with HPV testing after 12 months or repeat Pap smear at six and 12 months. Colposcopy is performed if abnormalities persist or worsen (see "Follow up testing" abovesee "Follow up testing" above). HPV testing is preferred because it is as effective as Pap smear but requires fewer visits and less need for colposcopy. Treatment to remove or destroy the abnormal cells (See "Patient information: Treatment of abnormal Pap smears"). Repeat colposcopy and Pap smear at 12 months.
Since many of these lesions will heal without treatment, some women prefer to delay treatment and have close monitoring. Treatment is the best option if LSIL persists, if the woman would have difficulty remembering to follow-up every six months, if the lesion is large (large lesions usually persist), if the lesion extends into the inner cervix (where it is difficult to see), or if the patient prefers treatment.
HIGH-GRADE SQUAMOUS LESION (HSIL) — These are moderate to severe changes in the cells of the cervix that may be precancerous (show picture 1). Approximately 20 percent of women will develop cervical cancer over a period of several years if no treatment is given.
A number of terms are used to describe high grade lesions, including CIN 2 and 3, moderate and severe dysplasia, and carcinoma in situ (CIS).
Follow up of HSIL — All women with high-grade lesions (HSIL) should have a colposcopy and biopsy. If colposcopy does not detect a high grade abnormality, close follow-up, further testing, and/or treatment may be recommended.
Treatment of HSIL — Women with high grade abnormalities should be treated because approximately 20 percent of untreated abnormalities will develop into invasive cancer. The most common treatment involves removal (excision) of the abnormal area of the cervix. (See "Patient information: Treatment of abnormal Pap smears").
Adolescent patients may be able to delay treatment of HSIL because, in this age group, there is a good chance that the abnormal area will heal without treatment. Close follow up is required, including colposcopy and Pap smear every four to six months. To delay treatment, the provider must be able to see the entire cervix during colposcopy and a test of the inner cervix (called endocervical curettage) must be negative.
Likewise, for pregnant women with HSIL, treatment is often delayed until after delivery. Colposcopy and Pap smear are generally performed several times during the pregnancy.
SQUAMOUS CELL CARCINOMA — Squamous cell carcinoma is the medical term for cervical cancer. Women with this result require a biopsy, which is usually performed with colposcopy. If biopsy confirms that cancerous cells are present, treatment is strongly recommended. The diagnosis and treatment of early stage cervical cancer is discussed in a separate topic review. (See "Patient information: Treatment of early stage cervical cancer").
GLANDULAR CELL ABNORMALITIES — Glandular cells develop from the inside the cervix (called the endocervical canal). Glandular cells can also come from the endometrium (lining of the uterus), the fallopian tube, or the ovary. Women with abnormal glandular cells need to have further testing to determine the source of the abnormality, if cancer or precancer is present, and to determine if treatment is needed.
Follow up testing — All women with atypical glandular cells (AGC) require further testing (colposcopy, biopsy, endometrial biopsy). This is because 10 to 40 percent of women with atypical glandular cells have precancerous or cancerous cells when evaluated by colposcopy and biopsy.
Treatment — Treatment of AGC depends upon the underlying abnormality and may involve monitoring, removal of a large part of the inner cervix, or less commonly, hysterectomy. (See "Patient information: Treatment of abnormal Pap smears").
PREVENTING CERVICAL CANCER
HPV vaccine — A vaccine (Gardasil®) is now available to help prevent infection with some types of HPV (types 6, 11, 16, and 18). Approximately 70 percent of cervical cancers result from infection with HPV 16 and 18, and approximately 90 percent of cases of genital warts result from infection with HPV 6 and 11. The vaccine was proven to be safe and effective in several large clinical trials [1,2].
The vaccine is currently recommended for all females who are between ages 9 and 26 years. Decisions about the age at which to start HPV immunization have been guided by the age at which the greatest number of women is infected with HPV and estimates regarding how long the vaccine continues to prevent infection. While it is not known exactly how long the vaccine protects against HPV infection, clinical trials prove protection for at least four years [3]. Further study is underway to determine if a booster shot is needed after this time.
The vaccine has not been studied in women over 26 years old and thus its effectiveness is uncertain. Women over this age are more likely to have been exposed to the four types of HPV in the vaccine (6, 11, 16, and 18); the vaccine does not protect against HPV infection if the woman has previously been exposed.
The vaccine is given by injection and requires three doses; the first injection is followed by a second and third dose two and six months later.
It is not known if vaccination of men could help to reduce the incidence of cervical cancer in women. Studies are currently underway to address this question. The vaccine is not currently recommended during pregnancy.
Sexual contact — Avoiding sex or sexual contact is not a practical way to prevent infection with HPV. Condoms provide partial protection, but not complete protection because they do not cover all areas of the genitals. Having a limited number of sexual partners may reduce the risk of HPV infection.
Smoking cessation — Women who smoke cigarettes are at increased risk of developing cervical cancer [4]. Cigarette smoking and HPV infection increase the risk of developing high-grade squamous lesions. The risk of cervical cancer is increased two- to four-fold among cigarette smokers compared to nonsmokers.
Women who smoke and have an abnormal Pap smear can reduce their risk of cervical cancer by quitting smoking. (See "Patient information: Smoking cessation").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Cancer Institute
(www.nci.nih.gov)
American Society of Cytopathology
(www.cytopathology.org)
American Society for Colposcopy and Cervical Pathology
(www.asccp.org)
American Cancer Society
(www.cancer.org, search for HPV)
National HPV and Cervical Cancer Public Education Campaign
Telephone: 1-866-280-6605
(www.cervicalcancercampaign.org)
National Institute of Allergy and Infectious Diseases
(www.niaid.nih.gov/factsheets/stdhpv.htm)
Center for Disease Control and Prevention
(www.cdc.gov/)
American Social Health Association
(http://www.ashastd.org/)
[1-9]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Koutsky, LA, Ault, KA, Wheeler, CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002; 347:1645.
2. Harper, DM, Franco, EL, Wheeler, C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004; 364:1757.
3. Harper, DM, Franco, EL, Wheeler, CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367:1247.
4. Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer 2006; 118:1481.
5. Solomon, D, Davey, D, Kurman, R, et al. The 2001 bethesda system: terminology for reporting results of cervical cytology. JAMA 2002; 287:2114.
6. Wright, TC Jr, Cox, JT, Massad, LS, et al. 2001 consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002; 287:2120.
7. Human PAP illomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group. J Natl Cancer Inst 2000; 92:397.
8. ACOG Practice Bulletin #66: Management of Abnormal Cervical Cytology and Histology. Obstet Gynecol 2005; 106:645.
9. ACOG Committee Opinion No. 344: Human papillomavirus vaccination. Obstet Gynecol 2006; 108:699.
This topic reviews the anatomy of the cervix, factors that increase a woman's risk of having cervical precancer or cancer, tests to detect cervical abnormalities, and a description of both normal and abnormal Pap smear results. A separate topic is available that discusses treatment of abnormal Pap smears. (See "Patient information: Treatment of abnormal Pap smears").
ANATOMY OF THE CERVIX — The cervix is located at the lower end of the uterus (show figure 1). The surface of the cervix includes several layers of cells. Squamous cells make up the outer layer of the cervix and vagina.
The cervix also includes glandular (also called columnar) cells, which line the opening in the cervix. The region where the two cell types meet is called the "transformation" zone (show picture 1). The transformation zone is the region most likely to contain abnormal cells.
If more than one third of the layers contain abnormal cells, this is called high grade squamous intraepithelial lesion (HSIL or HGSIL) (show figure 2).
What is a Pap smear? — A Pap smear is a method of examining cells from the cervix. The traditional Pap smear (named after Dr. Papanicolaou) involved smearing the cervical cells onto a glass slide. More recently, liquid-based tests (eg, ThinPrep, SurePath) have become available; these tests place the sample of cervical cells into a vial containing a liquid preservative. In both types of test, the cells are viewed with a microscope to detect abnormalities.
Cervical cells may appear abnormal for a variety of reasons. For example, a woman may have low estrogen levels or a cervical infection, or she may have a precancerous area or even cervical cancer. If the Pap smear is abnormal, further testing is needed to determine what the abnormality is and if treatment is needed.
Who should have a Pap smear? — The first Pap smear should be done by age 21 years. For most women, a Pap smear is recommended every one to three years. For women who have a past history of abnormal Pap smears or who have risk factors for cervical cancer, testing is recommended once per year (see "Risk factors for cervical cancer" below).
Women who are older than 30 years who have no risk factors, a negative Pap smear three years in a row, and a negative HPV test may choose to have a Pap smear and HPV testing every three years rather than every year (see "HPV testing" below). Most experts feel that women who are at low risk for cervical cancer (eg, no past history of an abnormal Pap) can discontinue Pap smears by age 65 to 70 years.
How are Pap smears obtained? — Pap smears are performed during a pelvic examination. To perform the test, a healthcare provider uses an instrument (speculum) to view the cervix, which is located at the lower end of the uterus (show figure 1). The provider sweeps the surface of the cervix and inner cervix (called the endocervical canal) with a soft brush or small spatula to collect cervical cells. This is not painful.
Pap smear accuracy — Most Pap smears can accurately identify women with abnormal cervical cells. However, the test is not perfect, and it misses between 5 and 25 percent of women with abnormalities. These women are said to have a false negative result. There are several important points to consider when discussing false negative results: Many false negative results are due to difficulty in collecting a sufficient number of cervical cells, not errors in reading the smear. It may be difficult to collect cervical cells if the cervix is hard to find during a pelvic examination, if the abnormal area is very small or high up inside the cervix, if only a few cervical cells are obtained, if the specimen dries too quickly, if the patient douches or has sexual intercourse before the examination, or if the woman is bleeding or has an infection at the time of the Pap smear. If a woman has a normal result three years in a row, then it is unlikely that an abnormality has been missed. The frequency of screening for cervical cancer can then be spread out (see "Who should have a Pap smear?" above). If a new lesion develops in a woman who is only tested every three years, it will be found before it becomes serious because it takes years for a new abnormality to develop into a high-grade precancer or cervical cancer. It usually takes many years for precancerous cervical cells to progress to cancer, and progression to cancer does not always occur.
RISK FACTORS FOR CERVICAL CANCER — The most important risk factor for cervical cancer is infection with the human papillomavirus (HPV). Other factors that increase the risk of cervical cancer include sexual intercourse, use of tobacco (eg, cigarettes), use of birth control pills, and a weakened immune system (eg, due to HIV infection or certain medications) (show table 1).
Human papillomavirus — Infection of the cervix with certain types of human papillomavirus (HPV) is the most significant risk factor for cervical abnormalities and cancer. Over 100 different types of HPV have been identified, however not all types infect the cervix or cause cancer. Researchers have labeled the HPV types as being high or low risk for causing cervical cancer. HPV types 6 and 11 can cause warts and are low-risk types because they rarely cause cervical cancer; types 16 and 18 are considered high-risk types because they may cause cervical cancer in some women. (See "Patient information: Condyloma (genital warts) in women").
HPV is spread by direct skin-to-skin contact, including sexual intercourse, oral sex, anal sex, or any other contact involving the genital area (eg, hand to genital contact). It is not possible to become infected with HPV by touching an object, such as a toilet seat.
Most persons who are infected with HPV have no signs or symptoms. Most HPV infections are temporary and resolve within two years. When the virus persists (in 10 to 20 percent of cases), there is a higher likelihood of developing cervical cell abnormalities and cancer. However, it usually takes several years for HPV infection to cause cervical cancer (see "HPV testing" below).
Sexual history — Cervical cancer is rare in women who have never had sexual intercourse. Cervical cancer is more common in women who have had more than one sexual partner or whose partners have more than one sexual partner. Other risk factors include: HIV infection, sexual intercourse before age 17, or a history of sexually transmitted diseases (eg, genital herpes or Chlamydia).
Tobacco use — Smoking cigarettes increases the risk of cervical cancer and precancer by up to seven times that of women who do not smoke. This is believed to occur because cancer-causing products from tobacco are secreted into the cervical mucous. Stopping smoking can decrease this risk. (See "Patient information: Smoking cessation").
Birth control with estrogen — Woman who use a birth control method that contain estrogen (eg, pills, patch) have a slightly higher risk of cervical precancers and cancers compared to women who do not take them (show table 1). The risk of cervical cancer related to birth control is small, and is related to infection with HPV. Thus, women who take a birth control with estrogen but are not infected with HPV have no increased risk of cervical cancer or precancer.
The reason that oral contraceptives increase the risk of cervical cancer is not clear. Higher levels of estrogen may causes changes in the cervix that increase the growth of cells that develop as a result of the HPV infection.
However, birth control with estrogen has a number of benefits, including a reduced risk of ovarian and uterine cancer and decreased pain and bleeding with menstrual periods. Women should discuss all the risks and benefits of this type of birth control with a healthcare provider. (See "Patient information: Hormonal methods of birth control").
Weakened immune system — Normally, the immune system works to protect the body from illness and infection, including the infection caused by human papillomavirus. Women with a weakened immune system have a significantly increased risk of cancers and precancers of the cervix.
A number of factors can weaken the immune system, including HIV infection, prolonged use of glucocorticoids (eg, prednisone), and use of medications to prevent rejection after organ transplantation.
PAP SMEAR RESULTS — The information reported in a Pap smear is described in table 2 (show table 2A-B). Pap smear results may be reported as:
Negative — Pap smears that have no abnormal, precancerous, or cancerous cells are labeled as "Negative for intraepithelial lesion or malignancy".
Smears that are negative can show other conditions, such as a vaginal infection (Trichomoniasis, yeast, herpes, or bacterial vaginosis) or cellular changes related to vaginal dryness, radiation therapy, or an intrauterine device (IUD) string. In some situations, further testing and/or treatment are needed.
Abnormal results — A number of medical terms are used to describe abnormalities of the cervix, including dysplasia, squamous intraepithelial lesion, and intraepithelial neoplasia. These terms all mean that the abnormality is confined to the surface or glandular lining of the cervix.
Follow up testing — Further testing is often needed after an abnormal Pap smear. The most common tests include HPV testing and colposcopy.
HPV testing — HPV testing is recommended only in particular circumstances: If the Pap smear shows a specific abnormality (for example, atypical squamous cells of uncertain significance, or ASC-US), HPV testing is then performed. This is called reflex testing.
Testing every woman for HPV is not recommended because of the risk of false positive results (when the HPV test was falsely positive and the Pap smear was negative). It is likely that many women develop HPV infections that resolve spontaneously. Having a false positive result would lead to unnecessary follow-up testing and anxiety for many women.
Colposcopy — Colposcopy is an office procedure that allows a clinician to closely examine the cervix. It is commonly performed after an abnormal Pap smear. Colposcopy is performed similar to a pelvic examination, while the woman lies on an exam table. A speculum is used to view the cervix, and the viewing device (called a colposcope) remains outside the woman's body (show picture 2).
The colposcope magnifies the appearance of the cervix 10 times. This allows the clinician to better see the location and size of any abnormalities, and also to see any changes in the capillaries (small blood vessels) on the surface of the cervix. Capillary changes are not detected by cervical cytology or HPV tests, but are important signs of the severity of cervical abnormalities.
Using the colposcope, a small piece of the abnormal area can be removed (biopsied). Anesthesia (numbing medicine) is not needed because the biopsy causes only mild discomfort or cramping. The biopsy is then examined with a microscope by a physician (called a pathologist). The results of the biopsy are usually available within one to two weeks.
Some women also need to have a biopsy of the inner cervix during colposcopy; this is called endocervical curettage. Endocervix refers to the inner cervix and curettage means scraping.
ATYPICAL SQUAMOUS CELLS (ASC) — A Pap smear may be read as atypical when cervical cells are not completely normal but are not thought to be precancerous. Further testing of ASC is suggested because some women (5 to 17 percent) have a precancerous lesion that is seen when colposcopy is performed. ASC is subdivided into ASC-US and ASC-H; ASC-H is more likely than ASC-US to be caused by a precancerous change.
ASC-US — There are three options for follow up of a single ASC-US result: Perform HPV testing. This is the preferred follow up for ASC-US. HPV testing can often be done at the same time as the Pap smear. This is convenient because a woman does not have to return for a second visit (see "HPV testing" above).
Women who test positive for high-risk HPV types are referred for colposcopy because they are at greater risk of having a precancerous lesion.
Women who test negative for HPV are not likely to have cervical precancer. These women should have a repeat Pap smear in one year. In most cases, the ASC-US resolves on its own. Repeat the Pap smear in four to six months. If this Pap is normal, it is repeated every four to six months until there have been two normal tests in a row. If the woman has two ASC-US results, she should have colposcopy.
For postmenopausal women, use of an estrogen treatment in the vagina for one month may be recommended after one ASC-US result; low estrogen levels in the vaginal and cervical tissues can cause mild cellular abnormalities that often revert to normal after estrogen treatment. Colposcopy should be performed if the woman has a second ASC-US result after use of estrogen therapy. Have colposcopy. This approach is preferred for women who are HIV positive or who have a weakened immune system because of the higher risk of a precancerous lesion (see "Colposcopy" above).
ASC-H — This finding requires further testing with colposcopy (see "Colposcopy" above).
LOW-GRADE SQUAMOUS LESION (LSIL) — These are mild cellular changes. Further testing is almost always recommended for women with LSIL because 15 percent of women with LSIL have a precancerous lesion that was not detected by the Pap smear.
A small number of women with low-grade changes will develop cancer over a period of several years if no treatment is performed. A large percentage (50 to 90 percent) of women with low-grade changes do not require treatment because the abnormality resolves on its own.
Low-grade abnormalities may be described with other names, including low-grade squamous intraepithelial lesions (LSIL), cervical intraepithelial neoplasia, grade 1 (CIN 1), and mild dysplasia.
Follow up of LSIL — Colposcopy is recommended for women with low-grade lesions (LSIL) (see "Colposcopy" above). Determining the size and location of the lesion with colposcopy can help to decide whether to treat the lesion or follow it over time. Large lesions are less likely to heal without treatment. Observing the extent and severity of the lesion with colposcopy is useful for establishing a baseline in women who are not treated.
However, LSIL in postmenopausal or adolescent women may be approached differently. A repeat Pap smear or HPV test may be recommended for adolescents; if the HPV is positive or the Pap smear continues to be abnormal, the adolescent is usually referred for colposcopy. Postmenopausal women may be treated with a course of estrogen cream, as described above (see "Atypical squamous cells (ASC)" above).
Treatment of LSIL — There are three options for management of LSIL: Close follow-up with HPV testing after 12 months or repeat Pap smear at six and 12 months. Colposcopy is performed if abnormalities persist or worsen (see "Follow up testing" abovesee "Follow up testing" above). HPV testing is preferred because it is as effective as Pap smear but requires fewer visits and less need for colposcopy. Treatment to remove or destroy the abnormal cells (See "Patient information: Treatment of abnormal Pap smears"). Repeat colposcopy and Pap smear at 12 months.
Since many of these lesions will heal without treatment, some women prefer to delay treatment and have close monitoring. Treatment is the best option if LSIL persists, if the woman would have difficulty remembering to follow-up every six months, if the lesion is large (large lesions usually persist), if the lesion extends into the inner cervix (where it is difficult to see), or if the patient prefers treatment.
HIGH-GRADE SQUAMOUS LESION (HSIL) — These are moderate to severe changes in the cells of the cervix that may be precancerous (show picture 1). Approximately 20 percent of women will develop cervical cancer over a period of several years if no treatment is given.
A number of terms are used to describe high grade lesions, including CIN 2 and 3, moderate and severe dysplasia, and carcinoma in situ (CIS).
Follow up of HSIL — All women with high-grade lesions (HSIL) should have a colposcopy and biopsy. If colposcopy does not detect a high grade abnormality, close follow-up, further testing, and/or treatment may be recommended.
Treatment of HSIL — Women with high grade abnormalities should be treated because approximately 20 percent of untreated abnormalities will develop into invasive cancer. The most common treatment involves removal (excision) of the abnormal area of the cervix. (See "Patient information: Treatment of abnormal Pap smears").
Adolescent patients may be able to delay treatment of HSIL because, in this age group, there is a good chance that the abnormal area will heal without treatment. Close follow up is required, including colposcopy and Pap smear every four to six months. To delay treatment, the provider must be able to see the entire cervix during colposcopy and a test of the inner cervix (called endocervical curettage) must be negative.
Likewise, for pregnant women with HSIL, treatment is often delayed until after delivery. Colposcopy and Pap smear are generally performed several times during the pregnancy.
SQUAMOUS CELL CARCINOMA — Squamous cell carcinoma is the medical term for cervical cancer. Women with this result require a biopsy, which is usually performed with colposcopy. If biopsy confirms that cancerous cells are present, treatment is strongly recommended. The diagnosis and treatment of early stage cervical cancer is discussed in a separate topic review. (See "Patient information: Treatment of early stage cervical cancer").
GLANDULAR CELL ABNORMALITIES — Glandular cells develop from the inside the cervix (called the endocervical canal). Glandular cells can also come from the endometrium (lining of the uterus), the fallopian tube, or the ovary. Women with abnormal glandular cells need to have further testing to determine the source of the abnormality, if cancer or precancer is present, and to determine if treatment is needed.
Follow up testing — All women with atypical glandular cells (AGC) require further testing (colposcopy, biopsy, endometrial biopsy). This is because 10 to 40 percent of women with atypical glandular cells have precancerous or cancerous cells when evaluated by colposcopy and biopsy.
Treatment — Treatment of AGC depends upon the underlying abnormality and may involve monitoring, removal of a large part of the inner cervix, or less commonly, hysterectomy. (See "Patient information: Treatment of abnormal Pap smears").
PREVENTING CERVICAL CANCER
HPV vaccine — A vaccine (Gardasil®) is now available to help prevent infection with some types of HPV (types 6, 11, 16, and 18). Approximately 70 percent of cervical cancers result from infection with HPV 16 and 18, and approximately 90 percent of cases of genital warts result from infection with HPV 6 and 11. The vaccine was proven to be safe and effective in several large clinical trials [1,2].
The vaccine is currently recommended for all females who are between ages 9 and 26 years. Decisions about the age at which to start HPV immunization have been guided by the age at which the greatest number of women is infected with HPV and estimates regarding how long the vaccine continues to prevent infection. While it is not known exactly how long the vaccine protects against HPV infection, clinical trials prove protection for at least four years [3]. Further study is underway to determine if a booster shot is needed after this time.
The vaccine has not been studied in women over 26 years old and thus its effectiveness is uncertain. Women over this age are more likely to have been exposed to the four types of HPV in the vaccine (6, 11, 16, and 18); the vaccine does not protect against HPV infection if the woman has previously been exposed.
The vaccine is given by injection and requires three doses; the first injection is followed by a second and third dose two and six months later.
It is not known if vaccination of men could help to reduce the incidence of cervical cancer in women. Studies are currently underway to address this question. The vaccine is not currently recommended during pregnancy.
Sexual contact — Avoiding sex or sexual contact is not a practical way to prevent infection with HPV. Condoms provide partial protection, but not complete protection because they do not cover all areas of the genitals. Having a limited number of sexual partners may reduce the risk of HPV infection.
Smoking cessation — Women who smoke cigarettes are at increased risk of developing cervical cancer [4]. Cigarette smoking and HPV infection increase the risk of developing high-grade squamous lesions. The risk of cervical cancer is increased two- to four-fold among cigarette smokers compared to nonsmokers.
Women who smoke and have an abnormal Pap smear can reduce their risk of cervical cancer by quitting smoking. (See "Patient information: Smoking cessation").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Cancer Institute
(www.nci.nih.gov)
American Society of Cytopathology
(www.cytopathology.org)
American Society for Colposcopy and Cervical Pathology
(www.asccp.org)
American Cancer Society
(www.cancer.org, search for HPV)
National HPV and Cervical Cancer Public Education Campaign
Telephone: 1-866-280-6605
(www.cervicalcancercampaign.org)
National Institute of Allergy and Infectious Diseases
(www.niaid.nih.gov/factsheets/stdhpv.htm)
Center for Disease Control and Prevention
(www.cdc.gov/)
American Social Health Association
(http://www.ashastd.org/)
[1-9]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Koutsky, LA, Ault, KA, Wheeler, CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002; 347:1645.
2. Harper, DM, Franco, EL, Wheeler, C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004; 364:1757.
3. Harper, DM, Franco, EL, Wheeler, CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367:1247.
4. Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer 2006; 118:1481.
5. Solomon, D, Davey, D, Kurman, R, et al. The 2001 bethesda system: terminology for reporting results of cervical cytology. JAMA 2002; 287:2114.
6. Wright, TC Jr, Cox, JT, Massad, LS, et al. 2001 consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002; 287:2120.
7. Human PAP illomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group. J Natl Cancer Inst 2000; 92:397.
8. ACOG Practice Bulletin #66: Management of Abnormal Cervical Cytology and Histology. Obstet Gynecol 2005; 106:645.
9. ACOG Committee Opinion No. 344: Human papillomavirus vaccination. Obstet Gynecol 2006; 108:699.
Screening for cervical cancer
INTRODUCTION — The Pap smear is a common test used to screen women for cervical precancer or cancer. However, most abnormal Pap smears are not due to cancer, but rather caused by infection or low estrogen levels.
This topic reviews the anatomy of the cervix, factors that increase a woman's risk of having cervical precancer or cancer, tests to detect cervical abnormalities, and a description of both normal and abnormal Pap smear results. A separate topic is available that discusses treatment of abnormal Pap smears. (See "Patient information: Treatment of abnormal Pap smears").
ANATOMY OF THE CERVIX — The cervix is located at the lower end of the uterus (show figure 1). The surface of the cervix includes several layers of cells. Squamous cells make up the outer layer of the cervix and vagina.
The cervix also includes glandular (also called columnar) cells, which line the opening in the cervix. The region where the two cell types meet is called the "transformation" zone (show picture 1). The transformation zone is the region most likely to contain abnormal cells.
If more than one third of the layers contain abnormal cells, this is called high grade squamous intraepithelial lesion (HSIL or HGSIL) (show figure 2).
What is a Pap smear? — A Pap smear is a method of examining cells from the cervix. The traditional Pap smear (named after Dr. Papanicolaou) involved smearing the cervical cells onto a glass slide. More recently, liquid-based tests (eg, ThinPrep, SurePath) have become available; these tests place the sample of cervical cells into a vial containing a liquid preservative. In both types of test, the cells are viewed with a microscope to detect abnormalities.
Cervical cells may appear abnormal for a variety of reasons. For example, a woman may have low estrogen levels or a cervical infection, or she may have a precancerous area or even cervical cancer. If the Pap smear is abnormal, further testing is needed to determine what the abnormality is and if treatment is needed.
Who should have a Pap smear? — The first Pap smear should be done by age 21 years. For most women, a Pap smear is recommended every one to three years. For women who have a past history of abnormal Pap smears or who have risk factors for cervical cancer, testing is recommended once per year (see "Risk factors for cervical cancer" below).
Women who are older than 30 years who have no risk factors, a negative Pap smear three years in a row, and a negative HPV test may choose to have a Pap smear and HPV testing every three years rather than every year (see "HPV testing" below). Most experts feel that women who are at low risk for cervical cancer (eg, no past history of an abnormal Pap) can discontinue Pap smears by age 65 to 70 years.
How are Pap smears obtained? — Pap smears are performed during a pelvic examination. To perform the test, a healthcare provider uses an instrument (speculum) to view the cervix, which is located at the lower end of the uterus (show figure 1). The provider sweeps the surface of the cervix and inner cervix (called the endocervical canal) with a soft brush or small spatula to collect cervical cells. This is not painful.
Pap smear accuracy — Most Pap smears can accurately identify women with abnormal cervical cells. However, the test is not perfect, and it misses between 5 and 25 percent of women with abnormalities. These women are said to have a false negative result. There are several important points to consider when discussing false negative results: Many false negative results are due to difficulty in collecting a sufficient number of cervical cells, not errors in reading the smear. It may be difficult to collect cervical cells if the cervix is hard to find during a pelvic examination, if the abnormal area is very small or high up inside the cervix, if only a few cervical cells are obtained, if the specimen dries too quickly, if the patient douches or has sexual intercourse before the examination, or if the woman is bleeding or has an infection at the time of the Pap smear. If a woman has a normal result three years in a row, then it is unlikely that an abnormality has been missed. The frequency of screening for cervical cancer can then be spread out (see "Who should have a Pap smear?" above). If a new lesion develops in a woman who is only tested every three years, it will be found before it becomes serious because it takes years for a new abnormality to develop into a high-grade precancer or cervical cancer. It usually takes many years for precancerous cervical cells to progress to cancer, and progression to cancer does not always occur.
RISK FACTORS FOR CERVICAL CANCER — The most important risk factor for cervical cancer is infection with the human papillomavirus (HPV). Other factors that increase the risk of cervical cancer include sexual intercourse, use of tobacco (eg, cigarettes), use of birth control pills, and a weakened immune system (eg, due to HIV infection or certain medications) (show table 1).
Human papillomavirus — Infection of the cervix with certain types of human papillomavirus (HPV) is the most significant risk factor for cervical abnormalities and cancer. Over 100 different types of HPV have been identified, however not all types infect the cervix or cause cancer. Researchers have labeled the HPV types as being high or low risk for causing cervical cancer. HPV types 6 and 11 can cause warts and are low-risk types because they rarely cause cervical cancer; types 16 and 18 are considered high-risk types because they may cause cervical cancer in some women. (See "Patient information: Condyloma (genital warts) in women").
HPV is spread by direct skin-to-skin contact, including sexual intercourse, oral sex, anal sex, or any other contact involving the genital area (eg, hand to genital contact). It is not possible to become infected with HPV by touching an object, such as a toilet seat.
Most persons who are infected with HPV have no signs or symptoms. Most HPV infections are temporary and resolve within two years. When the virus persists (in 10 to 20 percent of cases), there is a higher likelihood of developing cervical cell abnormalities and cancer. However, it usually takes several years for HPV infection to cause cervical cancer (see "HPV testing" below).
Sexual history — Cervical cancer is rare in women who have never had sexual intercourse. Cervical cancer is more common in women who have had more than one sexual partner or whose partners have more than one sexual partner. Other risk factors include: HIV infection, sexual intercourse before age 17, or a history of sexually transmitted diseases (eg, genital herpes or Chlamydia).
Tobacco use — Smoking cigarettes increases the risk of cervical cancer and precancer by up to seven times that of women who do not smoke. This is believed to occur because cancer-causing products from tobacco are secreted into the cervical mucous. Stopping smoking can decrease this risk. (See "Patient information: Smoking cessation").
Birth control with estrogen — Woman who use a birth control method that contain estrogen (eg, pills, patch) have a slightly higher risk of cervical precancers and cancers compared to women who do not take them (show table 1). The risk of cervical cancer related to birth control is small, and is related to infection with HPV. Thus, women who take a birth control with estrogen but are not infected with HPV have no increased risk of cervical cancer or precancer.
The reason that oral contraceptives increase the risk of cervical cancer is not clear. Higher levels of estrogen may causes changes in the cervix that increase the growth of cells that develop as a result of the HPV infection.
However, birth control with estrogen has a number of benefits, including a reduced risk of ovarian and uterine cancer and decreased pain and bleeding with menstrual periods. Women should discuss all the risks and benefits of this type of birth control with a healthcare provider. (See "Patient information: Hormonal methods of birth control").
Weakened immune system — Normally, the immune system works to protect the body from illness and infection, including the infection caused by human papillomavirus. Women with a weakened immune system have a significantly increased risk of cancers and precancers of the cervix.
A number of factors can weaken the immune system, including HIV infection, prolonged use of glucocorticoids (eg, prednisone), and use of medications to prevent rejection after organ transplantation.
PAP SMEAR RESULTS — The information reported in a Pap smear is described in table 2 (show table 2A-B). Pap smear results may be reported as:
Negative — Pap smears that have no abnormal, precancerous, or cancerous cells are labeled as "Negative for intraepithelial lesion or malignancy".
Smears that are negative can show other conditions, such as a vaginal infection (Trichomoniasis, yeast, herpes, or bacterial vaginosis) or cellular changes related to vaginal dryness, radiation therapy, or an intrauterine device (IUD) string. In some situations, further testing and/or treatment are needed.
Abnormal results — A number of medical terms are used to describe abnormalities of the cervix, including dysplasia, squamous intraepithelial lesion, and intraepithelial neoplasia. These terms all mean that the abnormality is confined to the surface or glandular lining of the cervix.
Follow up testing — Further testing is often needed after an abnormal Pap smear. The most common tests include HPV testing and colposcopy.
HPV testing — HPV testing is recommended only in particular circumstances: If the Pap smear shows a specific abnormality (for example, atypical squamous cells of uncertain significance, or ASC-US), HPV testing is then performed. This is called reflex testing.
Testing every woman for HPV is not recommended because of the risk of false positive results (when the HPV test was falsely positive and the Pap smear was negative). It is likely that many women develop HPV infections that resolve spontaneously. Having a false positive result would lead to unnecessary follow-up testing and anxiety for many women.
Colposcopy — Colposcopy is an office procedure that allows a clinician to closely examine the cervix. It is commonly performed after an abnormal Pap smear. Colposcopy is performed similar to a pelvic examination, while the woman lies on an exam table. A speculum is used to view the cervix, and the viewing device (called a colposcope) remains outside the woman's body (show picture 2).
The colposcope magnifies the appearance of the cervix 10 times. This allows the clinician to better see the location and size of any abnormalities, and also to see any changes in the capillaries (small blood vessels) on the surface of the cervix. Capillary changes are not detected by cervical cytology or HPV tests, but are important signs of the severity of cervical abnormalities.
Using the colposcope, a small piece of the abnormal area can be removed (biopsied). Anesthesia (numbing medicine) is not needed because the biopsy causes only mild discomfort or cramping. The biopsy is then examined with a microscope by a physician (called a pathologist). The results of the biopsy are usually available within one to two weeks.
Some women also need to have a biopsy of the inner cervix during colposcopy; this is called endocervical curettage. Endocervix refers to the inner cervix and curettage means scraping.
ATYPICAL SQUAMOUS CELLS (ASC) — A Pap smear may be read as atypical when cervical cells are not completely normal but are not thought to be precancerous. Further testing of ASC is suggested because some women (5 to 17 percent) have a precancerous lesion that is seen when colposcopy is performed. ASC is subdivided into ASC-US and ASC-H; ASC-H is more likely than ASC-US to be caused by a precancerous change.
ASC-US — There are three options for follow up of a single ASC-US result: Perform HPV testing. This is the preferred follow up for ASC-US. HPV testing can often be done at the same time as the Pap smear. This is convenient because a woman does not have to return for a second visit (see "HPV testing" above).
Women who test positive for high-risk HPV types are referred for colposcopy because they are at greater risk of having a precancerous lesion.
Women who test negative for HPV are not likely to have cervical precancer. These women should have a repeat Pap smear in one year. In most cases, the ASC-US resolves on its own. Repeat the Pap smear in four to six months. If this Pap is normal, it is repeated every four to six months until there have been two normal tests in a row. If the woman has two ASC-US results, she should have colposcopy.
For postmenopausal women, use of an estrogen treatment in the vagina for one month may be recommended after one ASC-US result; low estrogen levels in the vaginal and cervical tissues can cause mild cellular abnormalities that often revert to normal after estrogen treatment. Colposcopy should be performed if the woman has a second ASC-US result after use of estrogen therapy. Have colposcopy. This approach is preferred for women who are HIV positive or who have a weakened immune system because of the higher risk of a precancerous lesion (see "Colposcopy" above).
ASC-H — This finding requires further testing with colposcopy (see "Colposcopy" above).
LOW-GRADE SQUAMOUS LESION (LSIL) — These are mild cellular changes. Further testing is almost always recommended for women with LSIL because 15 percent of women with LSIL have a precancerous lesion that was not detected by the Pap smear.
A small number of women with low-grade changes will develop cancer over a period of several years if no treatment is performed. A large percentage (50 to 90 percent) of women with low-grade changes do not require treatment because the abnormality resolves on its own.
Low-grade abnormalities may be described with other names, including low-grade squamous intraepithelial lesions (LSIL), cervical intraepithelial neoplasia, grade 1 (CIN 1), and mild dysplasia.
Follow up of LSIL — Colposcopy is recommended for women with low-grade lesions (LSIL) (see "Colposcopy" above). Determining the size and location of the lesion with colposcopy can help to decide whether to treat the lesion or follow it over time. Large lesions are less likely to heal without treatment. Observing the extent and severity of the lesion with colposcopy is useful for establishing a baseline in women who are not treated.
However, LSIL in postmenopausal or adolescent women may be approached differently. A repeat Pap smear or HPV test may be recommended for adolescents; if the HPV is positive or the Pap smear continues to be abnormal, the adolescent is usually referred for colposcopy. Postmenopausal women may be treated with a course of estrogen cream, as described above (see "Atypical squamous cells (ASC)" above).
Treatment of LSIL — There are three options for management of LSIL: Close follow-up with HPV testing after 12 months or repeat Pap smear at six and 12 months. Colposcopy is performed if abnormalities persist or worsen (see "Follow up testing" abovesee "Follow up testing" above). HPV testing is preferred because it is as effective as Pap smear but requires fewer visits and less need for colposcopy. Treatment to remove or destroy the abnormal cells (See "Patient information: Treatment of abnormal Pap smears"). Repeat colposcopy and Pap smear at 12 months.
Since many of these lesions will heal without treatment, some women prefer to delay treatment and have close monitoring. Treatment is the best option if LSIL persists, if the woman would have difficulty remembering to follow-up every six months, if the lesion is large (large lesions usually persist), if the lesion extends into the inner cervix (where it is difficult to see), or if the patient prefers treatment.
HIGH-GRADE SQUAMOUS LESION (HSIL) — These are moderate to severe changes in the cells of the cervix that may be precancerous (show picture 1). Approximately 20 percent of women will develop cervical cancer over a period of several years if no treatment is given.
A number of terms are used to describe high grade lesions, including CIN 2 and 3, moderate and severe dysplasia, and carcinoma in situ (CIS).
Follow up of HSIL — All women with high-grade lesions (HSIL) should have a colposcopy and biopsy. If colposcopy does not detect a high grade abnormality, close follow-up, further testing, and/or treatment may be recommended.
Treatment of HSIL — Women with high grade abnormalities should be treated because approximately 20 percent of untreated abnormalities will develop into invasive cancer. The most common treatment involves removal (excision) of the abnormal area of the cervix. (See "Patient information: Treatment of abnormal Pap smears").
Adolescent patients may be able to delay treatment of HSIL because, in this age group, there is a good chance that the abnormal area will heal without treatment. Close follow up is required, including colposcopy and Pap smear every four to six months. To delay treatment, the provider must be able to see the entire cervix during colposcopy and a test of the inner cervix (called endocervical curettage) must be negative.
Likewise, for pregnant women with HSIL, treatment is often delayed until after delivery. Colposcopy and Pap smear are generally performed several times during the pregnancy.
SQUAMOUS CELL CARCINOMA — Squamous cell carcinoma is the medical term for cervical cancer. Women with this result require a biopsy, which is usually performed with colposcopy. If biopsy confirms that cancerous cells are present, treatment is strongly recommended. The diagnosis and treatment of early stage cervical cancer is discussed in a separate topic review. (See "Patient information: Treatment of early stage cervical cancer").
GLANDULAR CELL ABNORMALITIES — Glandular cells develop from the inside the cervix (called the endocervical canal). Glandular cells can also come from the endometrium (lining of the uterus), the fallopian tube, or the ovary. Women with abnormal glandular cells need to have further testing to determine the source of the abnormality, if cancer or precancer is present, and to determine if treatment is needed.
Follow up testing — All women with atypical glandular cells (AGC) require further testing (colposcopy, biopsy, endometrial biopsy). This is because 10 to 40 percent of women with atypical glandular cells have precancerous or cancerous cells when evaluated by colposcopy and biopsy.
Treatment — Treatment of AGC depends upon the underlying abnormality and may involve monitoring, removal of a large part of the inner cervix, or less commonly, hysterectomy. (See "Patient information: Treatment of abnormal Pap smears").
PREVENTING CERVICAL CANCER
HPV vaccine — A vaccine (Gardasil®) is now available to help prevent infection with some types of HPV (types 6, 11, 16, and 18). Approximately 70 percent of cervical cancers result from infection with HPV 16 and 18, and approximately 90 percent of cases of genital warts result from infection with HPV 6 and 11. The vaccine was proven to be safe and effective in several large clinical trials [1,2].
The vaccine is currently recommended for all females who are between ages 9 and 26 years. Decisions about the age at which to start HPV immunization have been guided by the age at which the greatest number of women is infected with HPV and estimates regarding how long the vaccine continues to prevent infection. While it is not known exactly how long the vaccine protects against HPV infection, clinical trials prove protection for at least four years [3]. Further study is underway to determine if a booster shot is needed after this time.
The vaccine has not been studied in women over 26 years old and thus its effectiveness is uncertain. Women over this age are more likely to have been exposed to the four types of HPV in the vaccine (6, 11, 16, and 18); the vaccine does not protect against HPV infection if the woman has previously been exposed.
The vaccine is given by injection and requires three doses; the first injection is followed by a second and third dose two and six months later.
It is not known if vaccination of men could help to reduce the incidence of cervical cancer in women. Studies are currently underway to address this question. The vaccine is not currently recommended during pregnancy.
Sexual contact — Avoiding sex or sexual contact is not a practical way to prevent infection with HPV. Condoms provide partial protection, but not complete protection because they do not cover all areas of the genitals. Having a limited number of sexual partners may reduce the risk of HPV infection.
Smoking cessation — Women who smoke cigarettes are at increased risk of developing cervical cancer [4]. Cigarette smoking and HPV infection increase the risk of developing high-grade squamous lesions. The risk of cervical cancer is increased two- to four-fold among cigarette smokers compared to nonsmokers.
Women who smoke and have an abnormal Pap smear can reduce their risk of cervical cancer by quitting smoking. (See "Patient information: Smoking cessation").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Cancer Institute
(www.nci.nih.gov)
American Society of Cytopathology
(www.cytopathology.org)
American Society for Colposcopy and Cervical Pathology
(www.asccp.org)
American Cancer Society
(www.cancer.org, search for HPV)
National HPV and Cervical Cancer Public Education Campaign
Telephone: 1-866-280-6605
(www.cervicalcancercampaign.org)
National Institute of Allergy and Infectious Diseases
(www.niaid.nih.gov/factsheets/stdhpv.htm)
Center for Disease Control and Prevention
(www.cdc.gov/)
American Social Health Association
(http://www.ashastd.org/)
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Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Koutsky, LA, Ault, KA, Wheeler, CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002; 347:1645.
2. Harper, DM, Franco, EL, Wheeler, C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004; 364:1757.
3. Harper, DM, Franco, EL, Wheeler, CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367:1247.
4. Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer 2006; 118:1481.
5. Solomon, D, Davey, D, Kurman, R, et al. The 2001 bethesda system: terminology for reporting results of cervical cytology. JAMA 2002; 287:2114.
6. Wright, TC Jr, Cox, JT, Massad, LS, et al. 2001 consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002; 287:2120.
7. Human PAP illomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group. J Natl Cancer Inst 2000; 92:397.
8. ACOG Practice Bulletin #66: Management of Abnormal Cervical Cytology and Histology. Obstet Gynecol 2005; 106:645.
9. ACOG Committee Opinion No. 344: Human papillomavirus vaccination. Obstet Gynecol 2006; 108:699.
This topic reviews the anatomy of the cervix, factors that increase a woman's risk of having cervical precancer or cancer, tests to detect cervical abnormalities, and a description of both normal and abnormal Pap smear results. A separate topic is available that discusses treatment of abnormal Pap smears. (See "Patient information: Treatment of abnormal Pap smears").
ANATOMY OF THE CERVIX — The cervix is located at the lower end of the uterus (show figure 1). The surface of the cervix includes several layers of cells. Squamous cells make up the outer layer of the cervix and vagina.
The cervix also includes glandular (also called columnar) cells, which line the opening in the cervix. The region where the two cell types meet is called the "transformation" zone (show picture 1). The transformation zone is the region most likely to contain abnormal cells.
If more than one third of the layers contain abnormal cells, this is called high grade squamous intraepithelial lesion (HSIL or HGSIL) (show figure 2).
What is a Pap smear? — A Pap smear is a method of examining cells from the cervix. The traditional Pap smear (named after Dr. Papanicolaou) involved smearing the cervical cells onto a glass slide. More recently, liquid-based tests (eg, ThinPrep, SurePath) have become available; these tests place the sample of cervical cells into a vial containing a liquid preservative. In both types of test, the cells are viewed with a microscope to detect abnormalities.
Cervical cells may appear abnormal for a variety of reasons. For example, a woman may have low estrogen levels or a cervical infection, or she may have a precancerous area or even cervical cancer. If the Pap smear is abnormal, further testing is needed to determine what the abnormality is and if treatment is needed.
Who should have a Pap smear? — The first Pap smear should be done by age 21 years. For most women, a Pap smear is recommended every one to three years. For women who have a past history of abnormal Pap smears or who have risk factors for cervical cancer, testing is recommended once per year (see "Risk factors for cervical cancer" below).
Women who are older than 30 years who have no risk factors, a negative Pap smear three years in a row, and a negative HPV test may choose to have a Pap smear and HPV testing every three years rather than every year (see "HPV testing" below). Most experts feel that women who are at low risk for cervical cancer (eg, no past history of an abnormal Pap) can discontinue Pap smears by age 65 to 70 years.
How are Pap smears obtained? — Pap smears are performed during a pelvic examination. To perform the test, a healthcare provider uses an instrument (speculum) to view the cervix, which is located at the lower end of the uterus (show figure 1). The provider sweeps the surface of the cervix and inner cervix (called the endocervical canal) with a soft brush or small spatula to collect cervical cells. This is not painful.
Pap smear accuracy — Most Pap smears can accurately identify women with abnormal cervical cells. However, the test is not perfect, and it misses between 5 and 25 percent of women with abnormalities. These women are said to have a false negative result. There are several important points to consider when discussing false negative results: Many false negative results are due to difficulty in collecting a sufficient number of cervical cells, not errors in reading the smear. It may be difficult to collect cervical cells if the cervix is hard to find during a pelvic examination, if the abnormal area is very small or high up inside the cervix, if only a few cervical cells are obtained, if the specimen dries too quickly, if the patient douches or has sexual intercourse before the examination, or if the woman is bleeding or has an infection at the time of the Pap smear. If a woman has a normal result three years in a row, then it is unlikely that an abnormality has been missed. The frequency of screening for cervical cancer can then be spread out (see "Who should have a Pap smear?" above). If a new lesion develops in a woman who is only tested every three years, it will be found before it becomes serious because it takes years for a new abnormality to develop into a high-grade precancer or cervical cancer. It usually takes many years for precancerous cervical cells to progress to cancer, and progression to cancer does not always occur.
RISK FACTORS FOR CERVICAL CANCER — The most important risk factor for cervical cancer is infection with the human papillomavirus (HPV). Other factors that increase the risk of cervical cancer include sexual intercourse, use of tobacco (eg, cigarettes), use of birth control pills, and a weakened immune system (eg, due to HIV infection or certain medications) (show table 1).
Human papillomavirus — Infection of the cervix with certain types of human papillomavirus (HPV) is the most significant risk factor for cervical abnormalities and cancer. Over 100 different types of HPV have been identified, however not all types infect the cervix or cause cancer. Researchers have labeled the HPV types as being high or low risk for causing cervical cancer. HPV types 6 and 11 can cause warts and are low-risk types because they rarely cause cervical cancer; types 16 and 18 are considered high-risk types because they may cause cervical cancer in some women. (See "Patient information: Condyloma (genital warts) in women").
HPV is spread by direct skin-to-skin contact, including sexual intercourse, oral sex, anal sex, or any other contact involving the genital area (eg, hand to genital contact). It is not possible to become infected with HPV by touching an object, such as a toilet seat.
Most persons who are infected with HPV have no signs or symptoms. Most HPV infections are temporary and resolve within two years. When the virus persists (in 10 to 20 percent of cases), there is a higher likelihood of developing cervical cell abnormalities and cancer. However, it usually takes several years for HPV infection to cause cervical cancer (see "HPV testing" below).
Sexual history — Cervical cancer is rare in women who have never had sexual intercourse. Cervical cancer is more common in women who have had more than one sexual partner or whose partners have more than one sexual partner. Other risk factors include: HIV infection, sexual intercourse before age 17, or a history of sexually transmitted diseases (eg, genital herpes or Chlamydia).
Tobacco use — Smoking cigarettes increases the risk of cervical cancer and precancer by up to seven times that of women who do not smoke. This is believed to occur because cancer-causing products from tobacco are secreted into the cervical mucous. Stopping smoking can decrease this risk. (See "Patient information: Smoking cessation").
Birth control with estrogen — Woman who use a birth control method that contain estrogen (eg, pills, patch) have a slightly higher risk of cervical precancers and cancers compared to women who do not take them (show table 1). The risk of cervical cancer related to birth control is small, and is related to infection with HPV. Thus, women who take a birth control with estrogen but are not infected with HPV have no increased risk of cervical cancer or precancer.
The reason that oral contraceptives increase the risk of cervical cancer is not clear. Higher levels of estrogen may causes changes in the cervix that increase the growth of cells that develop as a result of the HPV infection.
However, birth control with estrogen has a number of benefits, including a reduced risk of ovarian and uterine cancer and decreased pain and bleeding with menstrual periods. Women should discuss all the risks and benefits of this type of birth control with a healthcare provider. (See "Patient information: Hormonal methods of birth control").
Weakened immune system — Normally, the immune system works to protect the body from illness and infection, including the infection caused by human papillomavirus. Women with a weakened immune system have a significantly increased risk of cancers and precancers of the cervix.
A number of factors can weaken the immune system, including HIV infection, prolonged use of glucocorticoids (eg, prednisone), and use of medications to prevent rejection after organ transplantation.
PAP SMEAR RESULTS — The information reported in a Pap smear is described in table 2 (show table 2A-B). Pap smear results may be reported as:
Negative — Pap smears that have no abnormal, precancerous, or cancerous cells are labeled as "Negative for intraepithelial lesion or malignancy".
Smears that are negative can show other conditions, such as a vaginal infection (Trichomoniasis, yeast, herpes, or bacterial vaginosis) or cellular changes related to vaginal dryness, radiation therapy, or an intrauterine device (IUD) string. In some situations, further testing and/or treatment are needed.
Abnormal results — A number of medical terms are used to describe abnormalities of the cervix, including dysplasia, squamous intraepithelial lesion, and intraepithelial neoplasia. These terms all mean that the abnormality is confined to the surface or glandular lining of the cervix.
Follow up testing — Further testing is often needed after an abnormal Pap smear. The most common tests include HPV testing and colposcopy.
HPV testing — HPV testing is recommended only in particular circumstances: If the Pap smear shows a specific abnormality (for example, atypical squamous cells of uncertain significance, or ASC-US), HPV testing is then performed. This is called reflex testing.
Testing every woman for HPV is not recommended because of the risk of false positive results (when the HPV test was falsely positive and the Pap smear was negative). It is likely that many women develop HPV infections that resolve spontaneously. Having a false positive result would lead to unnecessary follow-up testing and anxiety for many women.
Colposcopy — Colposcopy is an office procedure that allows a clinician to closely examine the cervix. It is commonly performed after an abnormal Pap smear. Colposcopy is performed similar to a pelvic examination, while the woman lies on an exam table. A speculum is used to view the cervix, and the viewing device (called a colposcope) remains outside the woman's body (show picture 2).
The colposcope magnifies the appearance of the cervix 10 times. This allows the clinician to better see the location and size of any abnormalities, and also to see any changes in the capillaries (small blood vessels) on the surface of the cervix. Capillary changes are not detected by cervical cytology or HPV tests, but are important signs of the severity of cervical abnormalities.
Using the colposcope, a small piece of the abnormal area can be removed (biopsied). Anesthesia (numbing medicine) is not needed because the biopsy causes only mild discomfort or cramping. The biopsy is then examined with a microscope by a physician (called a pathologist). The results of the biopsy are usually available within one to two weeks.
Some women also need to have a biopsy of the inner cervix during colposcopy; this is called endocervical curettage. Endocervix refers to the inner cervix and curettage means scraping.
ATYPICAL SQUAMOUS CELLS (ASC) — A Pap smear may be read as atypical when cervical cells are not completely normal but are not thought to be precancerous. Further testing of ASC is suggested because some women (5 to 17 percent) have a precancerous lesion that is seen when colposcopy is performed. ASC is subdivided into ASC-US and ASC-H; ASC-H is more likely than ASC-US to be caused by a precancerous change.
ASC-US — There are three options for follow up of a single ASC-US result: Perform HPV testing. This is the preferred follow up for ASC-US. HPV testing can often be done at the same time as the Pap smear. This is convenient because a woman does not have to return for a second visit (see "HPV testing" above).
Women who test positive for high-risk HPV types are referred for colposcopy because they are at greater risk of having a precancerous lesion.
Women who test negative for HPV are not likely to have cervical precancer. These women should have a repeat Pap smear in one year. In most cases, the ASC-US resolves on its own. Repeat the Pap smear in four to six months. If this Pap is normal, it is repeated every four to six months until there have been two normal tests in a row. If the woman has two ASC-US results, she should have colposcopy.
For postmenopausal women, use of an estrogen treatment in the vagina for one month may be recommended after one ASC-US result; low estrogen levels in the vaginal and cervical tissues can cause mild cellular abnormalities that often revert to normal after estrogen treatment. Colposcopy should be performed if the woman has a second ASC-US result after use of estrogen therapy. Have colposcopy. This approach is preferred for women who are HIV positive or who have a weakened immune system because of the higher risk of a precancerous lesion (see "Colposcopy" above).
ASC-H — This finding requires further testing with colposcopy (see "Colposcopy" above).
LOW-GRADE SQUAMOUS LESION (LSIL) — These are mild cellular changes. Further testing is almost always recommended for women with LSIL because 15 percent of women with LSIL have a precancerous lesion that was not detected by the Pap smear.
A small number of women with low-grade changes will develop cancer over a period of several years if no treatment is performed. A large percentage (50 to 90 percent) of women with low-grade changes do not require treatment because the abnormality resolves on its own.
Low-grade abnormalities may be described with other names, including low-grade squamous intraepithelial lesions (LSIL), cervical intraepithelial neoplasia, grade 1 (CIN 1), and mild dysplasia.
Follow up of LSIL — Colposcopy is recommended for women with low-grade lesions (LSIL) (see "Colposcopy" above). Determining the size and location of the lesion with colposcopy can help to decide whether to treat the lesion or follow it over time. Large lesions are less likely to heal without treatment. Observing the extent and severity of the lesion with colposcopy is useful for establishing a baseline in women who are not treated.
However, LSIL in postmenopausal or adolescent women may be approached differently. A repeat Pap smear or HPV test may be recommended for adolescents; if the HPV is positive or the Pap smear continues to be abnormal, the adolescent is usually referred for colposcopy. Postmenopausal women may be treated with a course of estrogen cream, as described above (see "Atypical squamous cells (ASC)" above).
Treatment of LSIL — There are three options for management of LSIL: Close follow-up with HPV testing after 12 months or repeat Pap smear at six and 12 months. Colposcopy is performed if abnormalities persist or worsen (see "Follow up testing" abovesee "Follow up testing" above). HPV testing is preferred because it is as effective as Pap smear but requires fewer visits and less need for colposcopy. Treatment to remove or destroy the abnormal cells (See "Patient information: Treatment of abnormal Pap smears"). Repeat colposcopy and Pap smear at 12 months.
Since many of these lesions will heal without treatment, some women prefer to delay treatment and have close monitoring. Treatment is the best option if LSIL persists, if the woman would have difficulty remembering to follow-up every six months, if the lesion is large (large lesions usually persist), if the lesion extends into the inner cervix (where it is difficult to see), or if the patient prefers treatment.
HIGH-GRADE SQUAMOUS LESION (HSIL) — These are moderate to severe changes in the cells of the cervix that may be precancerous (show picture 1). Approximately 20 percent of women will develop cervical cancer over a period of several years if no treatment is given.
A number of terms are used to describe high grade lesions, including CIN 2 and 3, moderate and severe dysplasia, and carcinoma in situ (CIS).
Follow up of HSIL — All women with high-grade lesions (HSIL) should have a colposcopy and biopsy. If colposcopy does not detect a high grade abnormality, close follow-up, further testing, and/or treatment may be recommended.
Treatment of HSIL — Women with high grade abnormalities should be treated because approximately 20 percent of untreated abnormalities will develop into invasive cancer. The most common treatment involves removal (excision) of the abnormal area of the cervix. (See "Patient information: Treatment of abnormal Pap smears").
Adolescent patients may be able to delay treatment of HSIL because, in this age group, there is a good chance that the abnormal area will heal without treatment. Close follow up is required, including colposcopy and Pap smear every four to six months. To delay treatment, the provider must be able to see the entire cervix during colposcopy and a test of the inner cervix (called endocervical curettage) must be negative.
Likewise, for pregnant women with HSIL, treatment is often delayed until after delivery. Colposcopy and Pap smear are generally performed several times during the pregnancy.
SQUAMOUS CELL CARCINOMA — Squamous cell carcinoma is the medical term for cervical cancer. Women with this result require a biopsy, which is usually performed with colposcopy. If biopsy confirms that cancerous cells are present, treatment is strongly recommended. The diagnosis and treatment of early stage cervical cancer is discussed in a separate topic review. (See "Patient information: Treatment of early stage cervical cancer").
GLANDULAR CELL ABNORMALITIES — Glandular cells develop from the inside the cervix (called the endocervical canal). Glandular cells can also come from the endometrium (lining of the uterus), the fallopian tube, or the ovary. Women with abnormal glandular cells need to have further testing to determine the source of the abnormality, if cancer or precancer is present, and to determine if treatment is needed.
Follow up testing — All women with atypical glandular cells (AGC) require further testing (colposcopy, biopsy, endometrial biopsy). This is because 10 to 40 percent of women with atypical glandular cells have precancerous or cancerous cells when evaluated by colposcopy and biopsy.
Treatment — Treatment of AGC depends upon the underlying abnormality and may involve monitoring, removal of a large part of the inner cervix, or less commonly, hysterectomy. (See "Patient information: Treatment of abnormal Pap smears").
PREVENTING CERVICAL CANCER
HPV vaccine — A vaccine (Gardasil®) is now available to help prevent infection with some types of HPV (types 6, 11, 16, and 18). Approximately 70 percent of cervical cancers result from infection with HPV 16 and 18, and approximately 90 percent of cases of genital warts result from infection with HPV 6 and 11. The vaccine was proven to be safe and effective in several large clinical trials [1,2].
The vaccine is currently recommended for all females who are between ages 9 and 26 years. Decisions about the age at which to start HPV immunization have been guided by the age at which the greatest number of women is infected with HPV and estimates regarding how long the vaccine continues to prevent infection. While it is not known exactly how long the vaccine protects against HPV infection, clinical trials prove protection for at least four years [3]. Further study is underway to determine if a booster shot is needed after this time.
The vaccine has not been studied in women over 26 years old and thus its effectiveness is uncertain. Women over this age are more likely to have been exposed to the four types of HPV in the vaccine (6, 11, 16, and 18); the vaccine does not protect against HPV infection if the woman has previously been exposed.
The vaccine is given by injection and requires three doses; the first injection is followed by a second and third dose two and six months later.
It is not known if vaccination of men could help to reduce the incidence of cervical cancer in women. Studies are currently underway to address this question. The vaccine is not currently recommended during pregnancy.
Sexual contact — Avoiding sex or sexual contact is not a practical way to prevent infection with HPV. Condoms provide partial protection, but not complete protection because they do not cover all areas of the genitals. Having a limited number of sexual partners may reduce the risk of HPV infection.
Smoking cessation — Women who smoke cigarettes are at increased risk of developing cervical cancer [4]. Cigarette smoking and HPV infection increase the risk of developing high-grade squamous lesions. The risk of cervical cancer is increased two- to four-fold among cigarette smokers compared to nonsmokers.
Women who smoke and have an abnormal Pap smear can reduce their risk of cervical cancer by quitting smoking. (See "Patient information: Smoking cessation").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Cancer Institute
(www.nci.nih.gov)
American Society of Cytopathology
(www.cytopathology.org)
American Society for Colposcopy and Cervical Pathology
(www.asccp.org)
American Cancer Society
(www.cancer.org, search for HPV)
National HPV and Cervical Cancer Public Education Campaign
Telephone: 1-866-280-6605
(www.cervicalcancercampaign.org)
National Institute of Allergy and Infectious Diseases
(www.niaid.nih.gov/factsheets/stdhpv.htm)
Center for Disease Control and Prevention
(www.cdc.gov/)
American Social Health Association
(http://www.ashastd.org/)
[1-9]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Koutsky, LA, Ault, KA, Wheeler, CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002; 347:1645.
2. Harper, DM, Franco, EL, Wheeler, C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004; 364:1757.
3. Harper, DM, Franco, EL, Wheeler, CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367:1247.
4. Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer 2006; 118:1481.
5. Solomon, D, Davey, D, Kurman, R, et al. The 2001 bethesda system: terminology for reporting results of cervical cytology. JAMA 2002; 287:2114.
6. Wright, TC Jr, Cox, JT, Massad, LS, et al. 2001 consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002; 287:2120.
7. Human PAP illomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group. J Natl Cancer Inst 2000; 92:397.
8. ACOG Practice Bulletin #66: Management of Abnormal Cervical Cytology and Histology. Obstet Gynecol 2005; 106:645.
9. ACOG Committee Opinion No. 344: Human papillomavirus vaccination. Obstet Gynecol 2006; 108:699.
Screening for breast cancer
INTRODUCTION — Cancer screening refers to the use of tests to detect cancer at an early stage, before it causes symptoms and hopefully at a time when it is curable. More than 200,000 women in the United States are newly diagnosed with breast cancer each year. About 40,000 women die each year of breast cancer, making it second only to lung cancer in cancer deaths among women.
The death rate from breast cancer has declined about 20 percent over the past decade [1]. This is due, in part, to the ability of increased screening to find the disease at earlier stages when the chances of successful recovery are higher. In fact, there is more scientific evidence supporting the use of screening tests for breast cancer than for any other type of cancer.
The information presented here is for women at usual risk of breast cancer. Women with a known genetic mutation, like BRCA1 and BRCA2, or who have several close relatives with breast cancer should see "Patient information: Genetic testing for breast and ovarian cancer" for information about screening recommendations.
SCREENING METHODS — There are three main methods of screening for breast cancer: mammography, clinical breast examination, and breast self-examination.
Mammography — A mammogram is a breast x-ray that is the best screening test for reducing the risk of dying from breast cancer. Early concerns about the radiation exposure from mammograms have lessened with the use of modern mammography equipment that exposes the breast to extremely low levels of radiation. The current level of radiation exposure is unlikely to significantly increase the risk of developing breast cancer.
The cost of mammograms is covered by most private insurances, Medicare, and Medicaid. The American Cancer Society has information about low cost mammograms that are available in most communities (1-800-ACS-2345).
Technique — Before the mammogram, patients are asked to undress from the waist up and wear a hospital gown. Each breast is x-rayed individually. The breast is flattened between two panels, which allows the radiologist to more easily see abnormalities. This can be uncomfortable, though the discomfort lasts for only a few seconds. Mammograms are most uncomfortable when done just before or at the beginning of the menstrual period; women should try to avoid scheduling their mammogram at these times, if possible.
Findings — The mammogram is interpreted by a radiologist. Sometimes the radiologist is present at the time of the mammogram; in these cases, a patient may be asked to wait a few minutes while the radiologist determines if anything requires further evaluation. So, a woman may be asked to have additional x-rays. All mammography facilities are required to send results within 30 days; patients must be contacted within five days if the mammogram is abnormal.
Breast cancer cannot be diagnosed by mammography alone. Women usually require further testing (eg, ultrasound or biopsy) if the mammogram shows a mass, new calcium deposits, or other abnormal findings. These findings do not always mean that a cancer has been found. One study found that 11 percent of mammograms performed in the United States require additional evaluation; the area in question was not cancer in more than 90 percent of these cases [2].
The abnormalities that radiologists typically look for on mammograms are calcifications and masses (show figure 1 and show figure 2). Macrocalcifications are large calcium deposits that most often represent degenerative changes in the breast such as might occur with aging or with previous trauma or inflammation. Macrocalcifications are common, particularly in women over the age of 50, and generally do not require a biopsy. Microcalcifications are small specks of calcium that sometimes suggest the presence of breast cancer. Depending upon the shape and pattern of microcalcifications, the radiologist may recommend a biopsy of the affected area or a repeat mammogram in three to six months. Masses that appear on mammograms may represent cancer or a variety of benign disorders such as cysts or fibroadenomas. Ultrasound or needle aspiration is often recommended to determine if a mass is a cyst. If it is not a cyst, biopsy may be necessary.
Clinical breast examination — Clinical breast examination is the visual and manual examination of the breasts by a health care provider. Both clinical breast examination and mammography appear to be important; studies show that about 50 percent of breast cancers found on screening were detected by both examination and mammography. Five to 10 percent are detected with examination and missed by mammography, and about 40 percent are detected by mammography and missed by examination.
Clinical breast examination is typically performed at the yearly physical examination. Healthcare providers usually inspect the breasts for any changes in size or shape and then palpate (feel) the breasts and the area under both arms for any change in texture or the presence of lumps.
Breast self-examination — Breast self-examination is a means of detecting changes in your breasts. It typically is performed at the same time each month. For women who are menstruating, this may be about one week after the menstrual period ends, when the breasts are least lumpy. In postmenopausal women who are not menstruating, this may be on the same day each month.
Most studies have not found breast self-examination to be beneficial. One large randomized trial found breast self-examination did not reduce the risk of dying from breast cancer but did result in women undergoing more breast biopsies for benign lumps [3]. Nevertheless, some women feel that practicing breast self-examination regularly improves their ability to detect subtle changes that would otherwise not have been appreciated. Breast self-examination is not a substitute for mammography or clinical breast examination by a health care professional.
The studies that have been performed to date suggest that performing breast self-examination correctly is important. Patients who want to perform self-examinations should ask their health care provider to demonstrate how to do it and how to tell the difference between normal tissue and suspicious lumps.
Breast MRI — Magnetic resonance imaging (MRI) uses a strong magnet rather than x-rays or radiation to create a detailed image of a part of the body. Breast MRI may be recommended to aid in the diagnosis of breast cancer in selected situations (show radiograph 1) [4]. MRI is not recommended to detect breast cancer in women who do not have a high risk of breast cancer because of the increased risk of a falsely positive result (when the MRI shows a suspicious mass that is not cancer). In addition, MRI is not as good as mammogram in detecting certain breast conditions, such as ductal carcinoma in situ.
RECOMMENDATIONS — All major North American groups that make recommendations about breast cancer screening recommend routine screening with both mammography and clinical breast examination for women ages 50 years and older. There is controversy about routine screening among women in their 40s, although over time, more and more groups are recommending screening for women in their 40s as well. The American Cancer Society, American College of Radiology, American Medical Association, United States Preventive Services Task Force, and American College of Obstetrics and Gynecology all recommend starting routine screening at age 40 years. The US Preventive Services Task Force and American Academy of Family Physicians recommends screening mammography every one to two years for women ages 40 and older [5]. The American College of Physicians and The Canadian Task Force on the Periodic Health Examination recommend beginning routine screening at age 50 years. A 1997 National Institutes of Health Consensus Development Conference Panel Report on breast cancer screening in women ages 40 to 49 years recommended that women in this age group decide individually about breast cancer screening with their health care provider [6]. A 2007 guideline from the American College of Physicians makes a similar recommendation [7].
Defining routine screening — Most North American expert groups suggest that women over age 50 be screened every year. Groups that recommend screening for women in their 40s have tended to shift from recommending every one to two years to recommending every year because of the evidence of more rapid tumor growth in younger women.
There are no clear data on the effectiveness of routine screening mammography in women over age 70 years. Some researchers believe that mammography is less useful in these women because they have a reduced life expectancy and tumor growth is usually slower in older women. However, most expert groups recommend that because the risk for breast cancer increases as women age, routine screening should be continued as long as a woman has a life expectancy of at least 10 years. The recommended interval for women over the age of 70 is one to two years, depending upon a woman's individual risk of breast cancer. (See "Patient information: Risk factors for breast cancer").
The bottom line — All women should discuss mammograms with their clinician starting at age 40. Mammograms have the highest rate of detecting breast cancer. Virtually every well-performed study to date has found that screening mammography in women ages 50 and older reduces the risk of dying from breast cancer. A summary of trials found a 22 percent reduction in mortality in women in this age group who had regular mammography compared with women who did not [8]. For women in their 40s, the protection is somewhat less, both because breast cancer is less common and because it is harder to find with screening (examination and imaging tests) in younger women.
There are trade-offs between the benefits and risks of mammography in detecting: Breast cancers (that may end a woman's life prematurely) Precancerous lesions such as ductal carcinoma in situ (DCIS) (that often do not progress) False-positive results (that cause anxiety and potentially require unnecessary testing)
All women, especially those in their 40s, should discuss their situation with a health care provider and decide together when to start screening. Some useful information when considering mammography screening is presented in the figures (show figure 3A-3B). This figure shows what happens when 1000 women ages 40, 50, or 60 get annual mammograms for 10 years. It is possible to compare the number of women saved from death from breast cancer with the number of false-positive mammograms or diagnosis with DCIS.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Susan G. Komen Breast Cancer Foundation
(www.komen.org)
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Chu, KC, Tarone, RE, Kessler, LG, et al. Recent trends in U.S. breast cancer incidence, survival, and mortality rates. J Natl Cancer Inst 1996; 88:1571.
2. Brown, ML, Houn, F, Sickles, EA, et al. Screening mammography in community practice: positive predictive value of abnormal findings and yield of follow-up procedures. AJR Am J Roentgenol 1995; 165:1373.
3. Thomas, DB, Gao, DL, Ray, RM, et al. Randomized trial of breast self-examination in shanghai: final results. J Natl Cancer Inst 2002; 94:1445.
4. Saslow, D, Boetes, C, Burke, W, et al. American Cancer Society guidelines for breast cancer screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75.
5. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services, Third Edition. www.ahrq.gov/clinic/uspstfix.htm (Accessed 3/7/05).
6. National Institutes of Health Consensus Development Conference Statement Jan 21-23,1997. 103. Breast cancer screening for women ages 40-49. consensus.nih.gov/cons/103/103_intro.htm (Accessed October 26, 2005).
7. Qaseem, A, Snow, V, Sherif, K, et al. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2007; 146:511.
8. Humphrey, LL, Helfand, M, Chan, BK, Woolf, SH. Breast cancer screening: A summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2002; 137:347.
The death rate from breast cancer has declined about 20 percent over the past decade [1]. This is due, in part, to the ability of increased screening to find the disease at earlier stages when the chances of successful recovery are higher. In fact, there is more scientific evidence supporting the use of screening tests for breast cancer than for any other type of cancer.
The information presented here is for women at usual risk of breast cancer. Women with a known genetic mutation, like BRCA1 and BRCA2, or who have several close relatives with breast cancer should see "Patient information: Genetic testing for breast and ovarian cancer" for information about screening recommendations.
SCREENING METHODS — There are three main methods of screening for breast cancer: mammography, clinical breast examination, and breast self-examination.
Mammography — A mammogram is a breast x-ray that is the best screening test for reducing the risk of dying from breast cancer. Early concerns about the radiation exposure from mammograms have lessened with the use of modern mammography equipment that exposes the breast to extremely low levels of radiation. The current level of radiation exposure is unlikely to significantly increase the risk of developing breast cancer.
The cost of mammograms is covered by most private insurances, Medicare, and Medicaid. The American Cancer Society has information about low cost mammograms that are available in most communities (1-800-ACS-2345).
Technique — Before the mammogram, patients are asked to undress from the waist up and wear a hospital gown. Each breast is x-rayed individually. The breast is flattened between two panels, which allows the radiologist to more easily see abnormalities. This can be uncomfortable, though the discomfort lasts for only a few seconds. Mammograms are most uncomfortable when done just before or at the beginning of the menstrual period; women should try to avoid scheduling their mammogram at these times, if possible.
Findings — The mammogram is interpreted by a radiologist. Sometimes the radiologist is present at the time of the mammogram; in these cases, a patient may be asked to wait a few minutes while the radiologist determines if anything requires further evaluation. So, a woman may be asked to have additional x-rays. All mammography facilities are required to send results within 30 days; patients must be contacted within five days if the mammogram is abnormal.
Breast cancer cannot be diagnosed by mammography alone. Women usually require further testing (eg, ultrasound or biopsy) if the mammogram shows a mass, new calcium deposits, or other abnormal findings. These findings do not always mean that a cancer has been found. One study found that 11 percent of mammograms performed in the United States require additional evaluation; the area in question was not cancer in more than 90 percent of these cases [2].
The abnormalities that radiologists typically look for on mammograms are calcifications and masses (show figure 1 and show figure 2). Macrocalcifications are large calcium deposits that most often represent degenerative changes in the breast such as might occur with aging or with previous trauma or inflammation. Macrocalcifications are common, particularly in women over the age of 50, and generally do not require a biopsy. Microcalcifications are small specks of calcium that sometimes suggest the presence of breast cancer. Depending upon the shape and pattern of microcalcifications, the radiologist may recommend a biopsy of the affected area or a repeat mammogram in three to six months. Masses that appear on mammograms may represent cancer or a variety of benign disorders such as cysts or fibroadenomas. Ultrasound or needle aspiration is often recommended to determine if a mass is a cyst. If it is not a cyst, biopsy may be necessary.
Clinical breast examination — Clinical breast examination is the visual and manual examination of the breasts by a health care provider. Both clinical breast examination and mammography appear to be important; studies show that about 50 percent of breast cancers found on screening were detected by both examination and mammography. Five to 10 percent are detected with examination and missed by mammography, and about 40 percent are detected by mammography and missed by examination.
Clinical breast examination is typically performed at the yearly physical examination. Healthcare providers usually inspect the breasts for any changes in size or shape and then palpate (feel) the breasts and the area under both arms for any change in texture or the presence of lumps.
Breast self-examination — Breast self-examination is a means of detecting changes in your breasts. It typically is performed at the same time each month. For women who are menstruating, this may be about one week after the menstrual period ends, when the breasts are least lumpy. In postmenopausal women who are not menstruating, this may be on the same day each month.
Most studies have not found breast self-examination to be beneficial. One large randomized trial found breast self-examination did not reduce the risk of dying from breast cancer but did result in women undergoing more breast biopsies for benign lumps [3]. Nevertheless, some women feel that practicing breast self-examination regularly improves their ability to detect subtle changes that would otherwise not have been appreciated. Breast self-examination is not a substitute for mammography or clinical breast examination by a health care professional.
The studies that have been performed to date suggest that performing breast self-examination correctly is important. Patients who want to perform self-examinations should ask their health care provider to demonstrate how to do it and how to tell the difference between normal tissue and suspicious lumps.
Breast MRI — Magnetic resonance imaging (MRI) uses a strong magnet rather than x-rays or radiation to create a detailed image of a part of the body. Breast MRI may be recommended to aid in the diagnosis of breast cancer in selected situations (show radiograph 1) [4]. MRI is not recommended to detect breast cancer in women who do not have a high risk of breast cancer because of the increased risk of a falsely positive result (when the MRI shows a suspicious mass that is not cancer). In addition, MRI is not as good as mammogram in detecting certain breast conditions, such as ductal carcinoma in situ.
RECOMMENDATIONS — All major North American groups that make recommendations about breast cancer screening recommend routine screening with both mammography and clinical breast examination for women ages 50 years and older. There is controversy about routine screening among women in their 40s, although over time, more and more groups are recommending screening for women in their 40s as well. The American Cancer Society, American College of Radiology, American Medical Association, United States Preventive Services Task Force, and American College of Obstetrics and Gynecology all recommend starting routine screening at age 40 years. The US Preventive Services Task Force and American Academy of Family Physicians recommends screening mammography every one to two years for women ages 40 and older [5]. The American College of Physicians and The Canadian Task Force on the Periodic Health Examination recommend beginning routine screening at age 50 years. A 1997 National Institutes of Health Consensus Development Conference Panel Report on breast cancer screening in women ages 40 to 49 years recommended that women in this age group decide individually about breast cancer screening with their health care provider [6]. A 2007 guideline from the American College of Physicians makes a similar recommendation [7].
Defining routine screening — Most North American expert groups suggest that women over age 50 be screened every year. Groups that recommend screening for women in their 40s have tended to shift from recommending every one to two years to recommending every year because of the evidence of more rapid tumor growth in younger women.
There are no clear data on the effectiveness of routine screening mammography in women over age 70 years. Some researchers believe that mammography is less useful in these women because they have a reduced life expectancy and tumor growth is usually slower in older women. However, most expert groups recommend that because the risk for breast cancer increases as women age, routine screening should be continued as long as a woman has a life expectancy of at least 10 years. The recommended interval for women over the age of 70 is one to two years, depending upon a woman's individual risk of breast cancer. (See "Patient information: Risk factors for breast cancer").
The bottom line — All women should discuss mammograms with their clinician starting at age 40. Mammograms have the highest rate of detecting breast cancer. Virtually every well-performed study to date has found that screening mammography in women ages 50 and older reduces the risk of dying from breast cancer. A summary of trials found a 22 percent reduction in mortality in women in this age group who had regular mammography compared with women who did not [8]. For women in their 40s, the protection is somewhat less, both because breast cancer is less common and because it is harder to find with screening (examination and imaging tests) in younger women.
There are trade-offs between the benefits and risks of mammography in detecting: Breast cancers (that may end a woman's life prematurely) Precancerous lesions such as ductal carcinoma in situ (DCIS) (that often do not progress) False-positive results (that cause anxiety and potentially require unnecessary testing)
All women, especially those in their 40s, should discuss their situation with a health care provider and decide together when to start screening. Some useful information when considering mammography screening is presented in the figures (show figure 3A-3B). This figure shows what happens when 1000 women ages 40, 50, or 60 get annual mammograms for 10 years. It is possible to compare the number of women saved from death from breast cancer with the number of false-positive mammograms or diagnosis with DCIS.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Susan G. Komen Breast Cancer Foundation
(www.komen.org)
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Chu, KC, Tarone, RE, Kessler, LG, et al. Recent trends in U.S. breast cancer incidence, survival, and mortality rates. J Natl Cancer Inst 1996; 88:1571.
2. Brown, ML, Houn, F, Sickles, EA, et al. Screening mammography in community practice: positive predictive value of abnormal findings and yield of follow-up procedures. AJR Am J Roentgenol 1995; 165:1373.
3. Thomas, DB, Gao, DL, Ray, RM, et al. Randomized trial of breast self-examination in shanghai: final results. J Natl Cancer Inst 2002; 94:1445.
4. Saslow, D, Boetes, C, Burke, W, et al. American Cancer Society guidelines for breast cancer screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75.
5. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services, Third Edition. www.ahrq.gov/clinic/uspstfix.htm (Accessed 3/7/05).
6. National Institutes of Health Consensus Development Conference Statement Jan 21-23,1997. 103. Breast cancer screening for women ages 40-49. consensus.nih.gov/cons/103/103_intro.htm (Accessed October 26, 2005).
7. Qaseem, A, Snow, V, Sherif, K, et al. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2007; 146:511.
8. Humphrey, LL, Helfand, M, Chan, BK, Woolf, SH. Breast cancer screening: A summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2002; 137:347.
Screening for breast cancer
INTRODUCTION — Cancer screening refers to the use of tests to detect cancer at an early stage, before it causes symptoms and hopefully at a time when it is curable. More than 200,000 women in the United States are newly diagnosed with breast cancer each year. About 40,000 women die each year of breast cancer, making it second only to lung cancer in cancer deaths among women.
The death rate from breast cancer has declined about 20 percent over the past decade [1]. This is due, in part, to the ability of increased screening to find the disease at earlier stages when the chances of successful recovery are higher. In fact, there is more scientific evidence supporting the use of screening tests for breast cancer than for any other type of cancer.
The information presented here is for women at usual risk of breast cancer. Women with a known genetic mutation, like BRCA1 and BRCA2, or who have several close relatives with breast cancer should see "Patient information: Genetic testing for breast and ovarian cancer" for information about screening recommendations.
SCREENING METHODS — There are three main methods of screening for breast cancer: mammography, clinical breast examination, and breast self-examination.
Mammography — A mammogram is a breast x-ray that is the best screening test for reducing the risk of dying from breast cancer. Early concerns about the radiation exposure from mammograms have lessened with the use of modern mammography equipment that exposes the breast to extremely low levels of radiation. The current level of radiation exposure is unlikely to significantly increase the risk of developing breast cancer.
The cost of mammograms is covered by most private insurances, Medicare, and Medicaid. The American Cancer Society has information about low cost mammograms that are available in most communities (1-800-ACS-2345).
Technique — Before the mammogram, patients are asked to undress from the waist up and wear a hospital gown. Each breast is x-rayed individually. The breast is flattened between two panels, which allows the radiologist to more easily see abnormalities. This can be uncomfortable, though the discomfort lasts for only a few seconds. Mammograms are most uncomfortable when done just before or at the beginning of the menstrual period; women should try to avoid scheduling their mammogram at these times, if possible.
Findings — The mammogram is interpreted by a radiologist. Sometimes the radiologist is present at the time of the mammogram; in these cases, a patient may be asked to wait a few minutes while the radiologist determines if anything requires further evaluation. So, a woman may be asked to have additional x-rays. All mammography facilities are required to send results within 30 days; patients must be contacted within five days if the mammogram is abnormal.
Breast cancer cannot be diagnosed by mammography alone. Women usually require further testing (eg, ultrasound or biopsy) if the mammogram shows a mass, new calcium deposits, or other abnormal findings. These findings do not always mean that a cancer has been found. One study found that 11 percent of mammograms performed in the United States require additional evaluation; the area in question was not cancer in more than 90 percent of these cases [2].
The abnormalities that radiologists typically look for on mammograms are calcifications and masses (show figure 1 and show figure 2). Macrocalcifications are large calcium deposits that most often represent degenerative changes in the breast such as might occur with aging or with previous trauma or inflammation. Macrocalcifications are common, particularly in women over the age of 50, and generally do not require a biopsy. Microcalcifications are small specks of calcium that sometimes suggest the presence of breast cancer. Depending upon the shape and pattern of microcalcifications, the radiologist may recommend a biopsy of the affected area or a repeat mammogram in three to six months. Masses that appear on mammograms may represent cancer or a variety of benign disorders such as cysts or fibroadenomas. Ultrasound or needle aspiration is often recommended to determine if a mass is a cyst. If it is not a cyst, biopsy may be necessary.
Clinical breast examination — Clinical breast examination is the visual and manual examination of the breasts by a health care provider. Both clinical breast examination and mammography appear to be important; studies show that about 50 percent of breast cancers found on screening were detected by both examination and mammography. Five to 10 percent are detected with examination and missed by mammography, and about 40 percent are detected by mammography and missed by examination.
Clinical breast examination is typically performed at the yearly physical examination. Healthcare providers usually inspect the breasts for any changes in size or shape and then palpate (feel) the breasts and the area under both arms for any change in texture or the presence of lumps.
Breast self-examination — Breast self-examination is a means of detecting changes in your breasts. It typically is performed at the same time each month. For women who are menstruating, this may be about one week after the menstrual period ends, when the breasts are least lumpy. In postmenopausal women who are not menstruating, this may be on the same day each month.
Most studies have not found breast self-examination to be beneficial. One large randomized trial found breast self-examination did not reduce the risk of dying from breast cancer but did result in women undergoing more breast biopsies for benign lumps [3]. Nevertheless, some women feel that practicing breast self-examination regularly improves their ability to detect subtle changes that would otherwise not have been appreciated. Breast self-examination is not a substitute for mammography or clinical breast examination by a health care professional.
The studies that have been performed to date suggest that performing breast self-examination correctly is important. Patients who want to perform self-examinations should ask their health care provider to demonstrate how to do it and how to tell the difference between normal tissue and suspicious lumps.
Breast MRI — Magnetic resonance imaging (MRI) uses a strong magnet rather than x-rays or radiation to create a detailed image of a part of the body. Breast MRI may be recommended to aid in the diagnosis of breast cancer in selected situations (show radiograph 1) [4]. MRI is not recommended to detect breast cancer in women who do not have a high risk of breast cancer because of the increased risk of a falsely positive result (when the MRI shows a suspicious mass that is not cancer). In addition, MRI is not as good as mammogram in detecting certain breast conditions, such as ductal carcinoma in situ.
RECOMMENDATIONS — All major North American groups that make recommendations about breast cancer screening recommend routine screening with both mammography and clinical breast examination for women ages 50 years and older. There is controversy about routine screening among women in their 40s, although over time, more and more groups are recommending screening for women in their 40s as well. The American Cancer Society, American College of Radiology, American Medical Association, United States Preventive Services Task Force, and American College of Obstetrics and Gynecology all recommend starting routine screening at age 40 years. The US Preventive Services Task Force and American Academy of Family Physicians recommends screening mammography every one to two years for women ages 40 and older [5]. The American College of Physicians and The Canadian Task Force on the Periodic Health Examination recommend beginning routine screening at age 50 years. A 1997 National Institutes of Health Consensus Development Conference Panel Report on breast cancer screening in women ages 40 to 49 years recommended that women in this age group decide individually about breast cancer screening with their health care provider [6]. A 2007 guideline from the American College of Physicians makes a similar recommendation [7].
Defining routine screening — Most North American expert groups suggest that women over age 50 be screened every year. Groups that recommend screening for women in their 40s have tended to shift from recommending every one to two years to recommending every year because of the evidence of more rapid tumor growth in younger women.
There are no clear data on the effectiveness of routine screening mammography in women over age 70 years. Some researchers believe that mammography is less useful in these women because they have a reduced life expectancy and tumor growth is usually slower in older women. However, most expert groups recommend that because the risk for breast cancer increases as women age, routine screening should be continued as long as a woman has a life expectancy of at least 10 years. The recommended interval for women over the age of 70 is one to two years, depending upon a woman's individual risk of breast cancer. (See "Patient information: Risk factors for breast cancer").
The bottom line — All women should discuss mammograms with their clinician starting at age 40. Mammograms have the highest rate of detecting breast cancer. Virtually every well-performed study to date has found that screening mammography in women ages 50 and older reduces the risk of dying from breast cancer. A summary of trials found a 22 percent reduction in mortality in women in this age group who had regular mammography compared with women who did not [8]. For women in their 40s, the protection is somewhat less, both because breast cancer is less common and because it is harder to find with screening (examination and imaging tests) in younger women.
There are trade-offs between the benefits and risks of mammography in detecting: Breast cancers (that may end a woman's life prematurely) Precancerous lesions such as ductal carcinoma in situ (DCIS) (that often do not progress) False-positive results (that cause anxiety and potentially require unnecessary testing)
All women, especially those in their 40s, should discuss their situation with a health care provider and decide together when to start screening. Some useful information when considering mammography screening is presented in the figures (show figure 3A-3B). This figure shows what happens when 1000 women ages 40, 50, or 60 get annual mammograms for 10 years. It is possible to compare the number of women saved from death from breast cancer with the number of false-positive mammograms or diagnosis with DCIS.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Susan G. Komen Breast Cancer Foundation
(www.komen.org)
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Chu, KC, Tarone, RE, Kessler, LG, et al. Recent trends in U.S. breast cancer incidence, survival, and mortality rates. J Natl Cancer Inst 1996; 88:1571.
2. Brown, ML, Houn, F, Sickles, EA, et al. Screening mammography in community practice: positive predictive value of abnormal findings and yield of follow-up procedures. AJR Am J Roentgenol 1995; 165:1373.
3. Thomas, DB, Gao, DL, Ray, RM, et al. Randomized trial of breast self-examination in shanghai: final results. J Natl Cancer Inst 2002; 94:1445.
4. Saslow, D, Boetes, C, Burke, W, et al. American Cancer Society guidelines for breast cancer screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75.
5. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services, Third Edition. www.ahrq.gov/clinic/uspstfix.htm (Accessed 3/7/05).
6. National Institutes of Health Consensus Development Conference Statement Jan 21-23,1997. 103. Breast cancer screening for women ages 40-49. consensus.nih.gov/cons/103/103_intro.htm (Accessed October 26, 2005).
7. Qaseem, A, Snow, V, Sherif, K, et al. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2007; 146:511.
8. Humphrey, LL, Helfand, M, Chan, BK, Woolf, SH. Breast cancer screening: A summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2002; 137:347.
The death rate from breast cancer has declined about 20 percent over the past decade [1]. This is due, in part, to the ability of increased screening to find the disease at earlier stages when the chances of successful recovery are higher. In fact, there is more scientific evidence supporting the use of screening tests for breast cancer than for any other type of cancer.
The information presented here is for women at usual risk of breast cancer. Women with a known genetic mutation, like BRCA1 and BRCA2, or who have several close relatives with breast cancer should see "Patient information: Genetic testing for breast and ovarian cancer" for information about screening recommendations.
SCREENING METHODS — There are three main methods of screening for breast cancer: mammography, clinical breast examination, and breast self-examination.
Mammography — A mammogram is a breast x-ray that is the best screening test for reducing the risk of dying from breast cancer. Early concerns about the radiation exposure from mammograms have lessened with the use of modern mammography equipment that exposes the breast to extremely low levels of radiation. The current level of radiation exposure is unlikely to significantly increase the risk of developing breast cancer.
The cost of mammograms is covered by most private insurances, Medicare, and Medicaid. The American Cancer Society has information about low cost mammograms that are available in most communities (1-800-ACS-2345).
Technique — Before the mammogram, patients are asked to undress from the waist up and wear a hospital gown. Each breast is x-rayed individually. The breast is flattened between two panels, which allows the radiologist to more easily see abnormalities. This can be uncomfortable, though the discomfort lasts for only a few seconds. Mammograms are most uncomfortable when done just before or at the beginning of the menstrual period; women should try to avoid scheduling their mammogram at these times, if possible.
Findings — The mammogram is interpreted by a radiologist. Sometimes the radiologist is present at the time of the mammogram; in these cases, a patient may be asked to wait a few minutes while the radiologist determines if anything requires further evaluation. So, a woman may be asked to have additional x-rays. All mammography facilities are required to send results within 30 days; patients must be contacted within five days if the mammogram is abnormal.
Breast cancer cannot be diagnosed by mammography alone. Women usually require further testing (eg, ultrasound or biopsy) if the mammogram shows a mass, new calcium deposits, or other abnormal findings. These findings do not always mean that a cancer has been found. One study found that 11 percent of mammograms performed in the United States require additional evaluation; the area in question was not cancer in more than 90 percent of these cases [2].
The abnormalities that radiologists typically look for on mammograms are calcifications and masses (show figure 1 and show figure 2). Macrocalcifications are large calcium deposits that most often represent degenerative changes in the breast such as might occur with aging or with previous trauma or inflammation. Macrocalcifications are common, particularly in women over the age of 50, and generally do not require a biopsy. Microcalcifications are small specks of calcium that sometimes suggest the presence of breast cancer. Depending upon the shape and pattern of microcalcifications, the radiologist may recommend a biopsy of the affected area or a repeat mammogram in three to six months. Masses that appear on mammograms may represent cancer or a variety of benign disorders such as cysts or fibroadenomas. Ultrasound or needle aspiration is often recommended to determine if a mass is a cyst. If it is not a cyst, biopsy may be necessary.
Clinical breast examination — Clinical breast examination is the visual and manual examination of the breasts by a health care provider. Both clinical breast examination and mammography appear to be important; studies show that about 50 percent of breast cancers found on screening were detected by both examination and mammography. Five to 10 percent are detected with examination and missed by mammography, and about 40 percent are detected by mammography and missed by examination.
Clinical breast examination is typically performed at the yearly physical examination. Healthcare providers usually inspect the breasts for any changes in size or shape and then palpate (feel) the breasts and the area under both arms for any change in texture or the presence of lumps.
Breast self-examination — Breast self-examination is a means of detecting changes in your breasts. It typically is performed at the same time each month. For women who are menstruating, this may be about one week after the menstrual period ends, when the breasts are least lumpy. In postmenopausal women who are not menstruating, this may be on the same day each month.
Most studies have not found breast self-examination to be beneficial. One large randomized trial found breast self-examination did not reduce the risk of dying from breast cancer but did result in women undergoing more breast biopsies for benign lumps [3]. Nevertheless, some women feel that practicing breast self-examination regularly improves their ability to detect subtle changes that would otherwise not have been appreciated. Breast self-examination is not a substitute for mammography or clinical breast examination by a health care professional.
The studies that have been performed to date suggest that performing breast self-examination correctly is important. Patients who want to perform self-examinations should ask their health care provider to demonstrate how to do it and how to tell the difference between normal tissue and suspicious lumps.
Breast MRI — Magnetic resonance imaging (MRI) uses a strong magnet rather than x-rays or radiation to create a detailed image of a part of the body. Breast MRI may be recommended to aid in the diagnosis of breast cancer in selected situations (show radiograph 1) [4]. MRI is not recommended to detect breast cancer in women who do not have a high risk of breast cancer because of the increased risk of a falsely positive result (when the MRI shows a suspicious mass that is not cancer). In addition, MRI is not as good as mammogram in detecting certain breast conditions, such as ductal carcinoma in situ.
RECOMMENDATIONS — All major North American groups that make recommendations about breast cancer screening recommend routine screening with both mammography and clinical breast examination for women ages 50 years and older. There is controversy about routine screening among women in their 40s, although over time, more and more groups are recommending screening for women in their 40s as well. The American Cancer Society, American College of Radiology, American Medical Association, United States Preventive Services Task Force, and American College of Obstetrics and Gynecology all recommend starting routine screening at age 40 years. The US Preventive Services Task Force and American Academy of Family Physicians recommends screening mammography every one to two years for women ages 40 and older [5]. The American College of Physicians and The Canadian Task Force on the Periodic Health Examination recommend beginning routine screening at age 50 years. A 1997 National Institutes of Health Consensus Development Conference Panel Report on breast cancer screening in women ages 40 to 49 years recommended that women in this age group decide individually about breast cancer screening with their health care provider [6]. A 2007 guideline from the American College of Physicians makes a similar recommendation [7].
Defining routine screening — Most North American expert groups suggest that women over age 50 be screened every year. Groups that recommend screening for women in their 40s have tended to shift from recommending every one to two years to recommending every year because of the evidence of more rapid tumor growth in younger women.
There are no clear data on the effectiveness of routine screening mammography in women over age 70 years. Some researchers believe that mammography is less useful in these women because they have a reduced life expectancy and tumor growth is usually slower in older women. However, most expert groups recommend that because the risk for breast cancer increases as women age, routine screening should be continued as long as a woman has a life expectancy of at least 10 years. The recommended interval for women over the age of 70 is one to two years, depending upon a woman's individual risk of breast cancer. (See "Patient information: Risk factors for breast cancer").
The bottom line — All women should discuss mammograms with their clinician starting at age 40. Mammograms have the highest rate of detecting breast cancer. Virtually every well-performed study to date has found that screening mammography in women ages 50 and older reduces the risk of dying from breast cancer. A summary of trials found a 22 percent reduction in mortality in women in this age group who had regular mammography compared with women who did not [8]. For women in their 40s, the protection is somewhat less, both because breast cancer is less common and because it is harder to find with screening (examination and imaging tests) in younger women.
There are trade-offs between the benefits and risks of mammography in detecting: Breast cancers (that may end a woman's life prematurely) Precancerous lesions such as ductal carcinoma in situ (DCIS) (that often do not progress) False-positive results (that cause anxiety and potentially require unnecessary testing)
All women, especially those in their 40s, should discuss their situation with a health care provider and decide together when to start screening. Some useful information when considering mammography screening is presented in the figures (show figure 3A-3B). This figure shows what happens when 1000 women ages 40, 50, or 60 get annual mammograms for 10 years. It is possible to compare the number of women saved from death from breast cancer with the number of false-positive mammograms or diagnosis with DCIS.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Susan G. Komen Breast Cancer Foundation
(www.komen.org)
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Chu, KC, Tarone, RE, Kessler, LG, et al. Recent trends in U.S. breast cancer incidence, survival, and mortality rates. J Natl Cancer Inst 1996; 88:1571.
2. Brown, ML, Houn, F, Sickles, EA, et al. Screening mammography in community practice: positive predictive value of abnormal findings and yield of follow-up procedures. AJR Am J Roentgenol 1995; 165:1373.
3. Thomas, DB, Gao, DL, Ray, RM, et al. Randomized trial of breast self-examination in shanghai: final results. J Natl Cancer Inst 2002; 94:1445.
4. Saslow, D, Boetes, C, Burke, W, et al. American Cancer Society guidelines for breast cancer screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75.
5. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services, Third Edition. www.ahrq.gov/clinic/uspstfix.htm (Accessed 3/7/05).
6. National Institutes of Health Consensus Development Conference Statement Jan 21-23,1997. 103. Breast cancer screening for women ages 40-49. consensus.nih.gov/cons/103/103_intro.htm (Accessed October 26, 2005).
7. Qaseem, A, Snow, V, Sherif, K, et al. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2007; 146:511.
8. Humphrey, LL, Helfand, M, Chan, BK, Woolf, SH. Breast cancer screening: A summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2002; 137:347.
Prostate cancer screening
INTRODUCTION — Prostate cancer screening involves testing for cancer in men who have no symptoms of the disease. This testing can find cancer at an early stage, when it may be more easily and effectively treated. However, medical experts disagree about whether prostate cancer screening is right for all men, and it is not clear if the benefits of screening outweigh the risks.
This topic review is designed to discuss the advantages and disadvantages of prostate cancer screening. Men should talk with their healthcare provider to decide what is best in their individual situation.
WHAT IS PROSTATE CANCER? — Prostate cancer is a malignancy of the prostate, a small gland in men that is located below the bladder and above the rectum (show figure 1). The prostate produces seminal fluid that helps carry sperm during ejaculation.
According to the American Cancer Society, about 234,000 men in the United States will be diagnosed with prostate cancer in 2006, and over 27,000 will die from this disease. Prostate cancer is the second most commonly diagnosed malignancy after skin cancer.
Although many men are diagnosed with prostate cancer, most of them do not die from their cancer. While the lifetime risk of being diagnosed with prostate cancer is about 17 percent, only 3 percent of men die from the disease. Furthermore, autopsies show that 30 percent of men 50 years and older die with undiagnosed prostate cancer. This suggests that prostate cancer may grow so slowly that many men die of other causes before they even develop symptoms of prostate cancer.
RISK FACTORS
Age — All men are at risk for prostate cancer, but the risk greatly increases with older age. Doctors rarely find prostate cancer in men younger than 50 years old.
Ethnic background — Black men develop prostate cancer more often than white men. They also are more likely to die of prostate cancer than white men.
Family medical history — Men who have a first-degree relative (a father or brother) with prostate cancer are more likely to develop the disease.
Diet — A diet high in animal fat may increase a man's risk of prostate cancer.
PROSTATE CANCER SCREENING — Prostate cancer screening involves two tests: A physical test called a digital rectal exam (DRE) A blood test that measures prostate specific antigen (PSA).
Digital rectal examination — The DRE is performed by a healthcare provider in the office by inserting a gloved, lubricated finger into the rectum to feel for any lumps or irregularities in the prostate gland (show figure 2). DRE can detect some cancers that are missed by the PSA test. However, because it is not possible to reach all areas of the prostate, some tumors can go undetected using this screening method alone. Additionally, microscopic prostate cancers are impossible to detect by touch, no matter where they are located.
Prostate specific antigen — PSA is a protein produced by the prostate. The serum PSA test measures the amount of PSA in a sample of blood. Although many men with prostate cancer have an elevated PSA concentration (greater than 4.0 ng/mL), a high level does not necessarily mean there is a cancer. The most common cause for an elevated PSA is benign prostatic hyperplasia (BPH), a noncancerous enlargement of the prostate. Other benign causes include prostate infection (prostatitis) and trauma. Trauma may be caused by bicycle riding or sexual activity; thus, the PSA should not be measured for 48 hours after these activities.
Generally speaking, the higher the PSA, the greater the chance that a cancer is present. However, in some studies, over 20 percent of men with prostate cancer had a normal PSA (false-negative test), while up to 40 percent of men without cancer had an abnormal PSA (false-positive test). Overall, only 30 percent of men with abnormal values will have prostate cancer.
Thus, the PSA test is not 100 percent accurate. False-negative results can delay diagnosis until the cancer is more advanced and less likely to be curable. False-positive results, which are common, can cause anxiety and lead to further testing that is more expensive to perform and is uncomfortable for patients.
Refinements in PSA blood testing such as measuring PSA velocity (rate of change over time), PSA density (PSA per volume of prostate tissue), free (unbound) PSA, and complex (bound to protein) PSA are intended to increase the accuracy of PSA tests, but there is not general agreement about the additional benefits of these tests.
If the DRE or PSA test is positive — A positive DRE or PSA test is not a reason to panic; benign conditions are the most common causes for an abnormal test, particularly for PSA tests. On the other hand, a positive test should not be ignored. Other tests, like transrectal ultrasound and prostate biopsy, are needed to evaluate a positive DRE or PSA.
Transrectal ultrasound — Transrectal ultrasound can be done in an office, and no sedation or anesthesia is needed. A small probe, about the size of a finger, is inserted into the rectum, and uses sound waves that bounce off the prostate to create an echo. A computer translates these echoes into an image (called a sonogram) of the prostate. About 80 percent of cancers have an abnormal ultrasound image. Transrectal ultrasound can also help to guide a surgeon to biopsy any area that appears abnormal.
Prostate biopsy — Prostate biopsy is also performed without sedation or anesthesia. It is done by inserting a small device into the rectum that can take a small sample of any suspicious areas (found either with DRE or ultrasound). Tissue samples are also taken from the base, middle, and tip of each side of the prostate. Some men experience temporary, mild rectal bleeding or blood in the urine or semen after this procedure. Rarely, biopsy can cause heavy bleeding or infection.
Up to one in five men with a negative result on an initial biopsy may have cancer diagnosed after subsequent biopsies. In addition, prostate biopsy can detect clinically unimportant cancers that are unlikely to cause illness or death; subsequent treatment for these cancers can ultimately cause more harm than good.
Summary — No screening test for prostate cancer is perfect. Experts who favor it suggest that the best screening strategy combines DRE with PSA testing, followed by transrectal ultrasound-guided prostate biopsy if either test is positive.
PROS AND CONS OF SCREENING — There are a number of arguments for and against prostate cancer screening.
Arguments for screening — Experts in favor of prostate cancer screening cite the following arguments: Even though many men with prostate cancer have nonaggressive tumors and do not die of the disease, the cancer is so common that a substantial number of men die from the cancer every year and many more suffer from the complications of advanced disease. For men with an aggressive prostate cancer, the best chance for curing it is probably by finding it at an early stage through screening and then treating it with surgery or radiation. Studies have shown that men who have prostate cancer detected by PSA screening tend to have earlier-stage cancer than men who have a cancer detected by other means. (See "Patient information: Advanced prostate cancer" and see "Patient information: Treatment for early prostate cancer"). The five-year survival for men who have prostate cancer confined to the prostate gland (early stage) is nearly 100 percent; this drops to 30 percent for men whose cancer has spread to other areas of the body. Chemotherapy and radiation therapy are relatively ineffective once prostate cancer has spread outside the prostate gland. The available screening tests are not perfect, but they are fairly good compared with screening tests for some other cancers, and they are easy to perform. The death rate due to prostate cancer has declined in recent years. This may be due to increased screening or improvements in prostate cancer treatment, particularly for advanced cancers. The death rate may also have declined due to changes in the ways that physicians complete death certificates.
Arguments against screening — The main argument against screening is that it is not clear if screening and treatment help men live longer and/or avoid the complications of advanced prostate cancer. No well-performed studies have determined that prostate cancer screening in the general population saves lives. Studies are currently underway to answer this important question, but the results may not be available for some time.
Other arguments have also been made against screening: Because of the relatively high number of false-positive DRE and PSA tests, a number of screened men will undergo unnecessary further testing with transrectal ultrasound and prostate biopsy. These secondary tests are relatively safe to perform, but they are not totally without side effects, and they add further costs. The side effects of treatment for early prostate cancers that are detected with screening may be substantial. Surgery and radiation therapy are the most popular therapies, and both can cause erectile dysfunction, urinary incontinence, and bowel problems. Although there are some tools to predict which cancers are more aggressive than others, these tools are not always accurate.
Many prostate cancers detected with screening are unlikely to cause death or disability. Thus, a number of men will have to experience the side effects of surgery and radiation for cancers that would never have bothered them had they gone undetected. In other words, even if the screening process works and a cancer is detected, it is not clear in all cases that the treatment is more beneficial than harmful.
PREVENTION OF PROSTATE CANCER
Supplements — Studies suggest that vitamin E and selenium supplements may protect against prostate cancer, but there is not enough evidence to recommend these supplements to all men.
Medications — Finasteride (Proscar®) has been shown to reduce the risk of developing prostate cancer by about 25 percent. However, aggressive cancers were diagnosed more frequently during the first year in men treated with finasteride than in those taking a placebo (look-alike substitute that contains no medication) pill. The reasons for this finding are not clear. It is not clear if finasteride should be offered to men at high risk for prostate cancer.
RECOMMENDATIONS
Professional organizations — Major medical associations and societies have issued conflicting recommendations regarding screening, making it difficult for an individual to decide if screening is right. The United States Preventive Services Task Force [2] and many European cancer societies have not endorsed routine serum PSA screening for the early detection of prostate cancer, while the American Cancer Society [3] and American Urological Association [4] do recommend screening. With currently available data, it is not possible to determine if the benefits of screening outweigh the significant risks associated with treatment.
A number of studies are expected to be completed over the next several years that should help clarify this controversy. In the meantime, the American Cancer Society, American Urological Association, and American College of Physicians recommend that men have an open discussion with their clinician.
The best way to decide if prostate cancer screening is right is to: Consider individual prostate cancer risk factors Know the potential benefits and harms of screening, diagnosis, and treatment Talk to a clinician about concerns or questions.
For men who choose screening — If a man chooses to have screening, he should begin at age 50. Men with risk factors for prostate cancer (such as black men or a man with a father or brother who had prostate cancer) may want to begin screening at the age of 45.
Screening should continue yearly once it is started, though less frequent testing may be appropriate for some men with a low PSA. For men who choose screening, we suggest that those with a PSA level below 1.0 ng/mL consider having PSA testing every four years and that those with a higher PSA level consider having PSA testing annually. We suggest that men who choose screening have an annual digital rectal exam, regardless of their PSA level.
Screening not recommended — Screening should not be performed in men who are 75 years and older or who have serious health problems; these men are unlikely to live long enough to benefit from screening and/or treatment.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.cancer.gov/cancertopics/screening/prostate)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
US TOO! Prostate Cancer Education and Support
(www.ustoo.com/Early_Detection.asp)
[1-6]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Prostate cancer. National Cancer Institute. Web site: http://cancernet.nci.nih.gov/cancertopics/types/prostate.
2. Screening for prostate cancer: recommendation and rationale. Ann Intern Med 2002; 137:915.
3. Smith, RA, von Eschenbach, AC, Wender, R, et al. American Cancer Society Guidelines for the early detection of cancer: update of early detection guidelines for prostate, colorectal, and endometrial cancers. CA Cancer J Clin 2001; 51:38.
4. Prostate-specific antigen (PSA) best practice policy. American Urological Association (AUA). Oncology (Williston Park) 2000; 14:267.
5. Whittemore, AS, Cirillo, PM, Feldman, D, Cohn, BA. Prostate specific antigen levels in young adulthood predict prostate cancer risk: results from a cohort of Black and White Americans. J Urol 2005; 174:872.
6. Carter, HB. Prostate cancers in men with low PSA levels--must we find them?. N Engl J Med 2004; 350:2292.
This topic review is designed to discuss the advantages and disadvantages of prostate cancer screening. Men should talk with their healthcare provider to decide what is best in their individual situation.
WHAT IS PROSTATE CANCER? — Prostate cancer is a malignancy of the prostate, a small gland in men that is located below the bladder and above the rectum (show figure 1). The prostate produces seminal fluid that helps carry sperm during ejaculation.
According to the American Cancer Society, about 234,000 men in the United States will be diagnosed with prostate cancer in 2006, and over 27,000 will die from this disease. Prostate cancer is the second most commonly diagnosed malignancy after skin cancer.
Although many men are diagnosed with prostate cancer, most of them do not die from their cancer. While the lifetime risk of being diagnosed with prostate cancer is about 17 percent, only 3 percent of men die from the disease. Furthermore, autopsies show that 30 percent of men 50 years and older die with undiagnosed prostate cancer. This suggests that prostate cancer may grow so slowly that many men die of other causes before they even develop symptoms of prostate cancer.
RISK FACTORS
Age — All men are at risk for prostate cancer, but the risk greatly increases with older age. Doctors rarely find prostate cancer in men younger than 50 years old.
Ethnic background — Black men develop prostate cancer more often than white men. They also are more likely to die of prostate cancer than white men.
Family medical history — Men who have a first-degree relative (a father or brother) with prostate cancer are more likely to develop the disease.
Diet — A diet high in animal fat may increase a man's risk of prostate cancer.
PROSTATE CANCER SCREENING — Prostate cancer screening involves two tests: A physical test called a digital rectal exam (DRE) A blood test that measures prostate specific antigen (PSA).
Digital rectal examination — The DRE is performed by a healthcare provider in the office by inserting a gloved, lubricated finger into the rectum to feel for any lumps or irregularities in the prostate gland (show figure 2). DRE can detect some cancers that are missed by the PSA test. However, because it is not possible to reach all areas of the prostate, some tumors can go undetected using this screening method alone. Additionally, microscopic prostate cancers are impossible to detect by touch, no matter where they are located.
Prostate specific antigen — PSA is a protein produced by the prostate. The serum PSA test measures the amount of PSA in a sample of blood. Although many men with prostate cancer have an elevated PSA concentration (greater than 4.0 ng/mL), a high level does not necessarily mean there is a cancer. The most common cause for an elevated PSA is benign prostatic hyperplasia (BPH), a noncancerous enlargement of the prostate. Other benign causes include prostate infection (prostatitis) and trauma. Trauma may be caused by bicycle riding or sexual activity; thus, the PSA should not be measured for 48 hours after these activities.
Generally speaking, the higher the PSA, the greater the chance that a cancer is present. However, in some studies, over 20 percent of men with prostate cancer had a normal PSA (false-negative test), while up to 40 percent of men without cancer had an abnormal PSA (false-positive test). Overall, only 30 percent of men with abnormal values will have prostate cancer.
Thus, the PSA test is not 100 percent accurate. False-negative results can delay diagnosis until the cancer is more advanced and less likely to be curable. False-positive results, which are common, can cause anxiety and lead to further testing that is more expensive to perform and is uncomfortable for patients.
Refinements in PSA blood testing such as measuring PSA velocity (rate of change over time), PSA density (PSA per volume of prostate tissue), free (unbound) PSA, and complex (bound to protein) PSA are intended to increase the accuracy of PSA tests, but there is not general agreement about the additional benefits of these tests.
If the DRE or PSA test is positive — A positive DRE or PSA test is not a reason to panic; benign conditions are the most common causes for an abnormal test, particularly for PSA tests. On the other hand, a positive test should not be ignored. Other tests, like transrectal ultrasound and prostate biopsy, are needed to evaluate a positive DRE or PSA.
Transrectal ultrasound — Transrectal ultrasound can be done in an office, and no sedation or anesthesia is needed. A small probe, about the size of a finger, is inserted into the rectum, and uses sound waves that bounce off the prostate to create an echo. A computer translates these echoes into an image (called a sonogram) of the prostate. About 80 percent of cancers have an abnormal ultrasound image. Transrectal ultrasound can also help to guide a surgeon to biopsy any area that appears abnormal.
Prostate biopsy — Prostate biopsy is also performed without sedation or anesthesia. It is done by inserting a small device into the rectum that can take a small sample of any suspicious areas (found either with DRE or ultrasound). Tissue samples are also taken from the base, middle, and tip of each side of the prostate. Some men experience temporary, mild rectal bleeding or blood in the urine or semen after this procedure. Rarely, biopsy can cause heavy bleeding or infection.
Up to one in five men with a negative result on an initial biopsy may have cancer diagnosed after subsequent biopsies. In addition, prostate biopsy can detect clinically unimportant cancers that are unlikely to cause illness or death; subsequent treatment for these cancers can ultimately cause more harm than good.
Summary — No screening test for prostate cancer is perfect. Experts who favor it suggest that the best screening strategy combines DRE with PSA testing, followed by transrectal ultrasound-guided prostate biopsy if either test is positive.
PROS AND CONS OF SCREENING — There are a number of arguments for and against prostate cancer screening.
Arguments for screening — Experts in favor of prostate cancer screening cite the following arguments: Even though many men with prostate cancer have nonaggressive tumors and do not die of the disease, the cancer is so common that a substantial number of men die from the cancer every year and many more suffer from the complications of advanced disease. For men with an aggressive prostate cancer, the best chance for curing it is probably by finding it at an early stage through screening and then treating it with surgery or radiation. Studies have shown that men who have prostate cancer detected by PSA screening tend to have earlier-stage cancer than men who have a cancer detected by other means. (See "Patient information: Advanced prostate cancer" and see "Patient information: Treatment for early prostate cancer"). The five-year survival for men who have prostate cancer confined to the prostate gland (early stage) is nearly 100 percent; this drops to 30 percent for men whose cancer has spread to other areas of the body. Chemotherapy and radiation therapy are relatively ineffective once prostate cancer has spread outside the prostate gland. The available screening tests are not perfect, but they are fairly good compared with screening tests for some other cancers, and they are easy to perform. The death rate due to prostate cancer has declined in recent years. This may be due to increased screening or improvements in prostate cancer treatment, particularly for advanced cancers. The death rate may also have declined due to changes in the ways that physicians complete death certificates.
Arguments against screening — The main argument against screening is that it is not clear if screening and treatment help men live longer and/or avoid the complications of advanced prostate cancer. No well-performed studies have determined that prostate cancer screening in the general population saves lives. Studies are currently underway to answer this important question, but the results may not be available for some time.
Other arguments have also been made against screening: Because of the relatively high number of false-positive DRE and PSA tests, a number of screened men will undergo unnecessary further testing with transrectal ultrasound and prostate biopsy. These secondary tests are relatively safe to perform, but they are not totally without side effects, and they add further costs. The side effects of treatment for early prostate cancers that are detected with screening may be substantial. Surgery and radiation therapy are the most popular therapies, and both can cause erectile dysfunction, urinary incontinence, and bowel problems. Although there are some tools to predict which cancers are more aggressive than others, these tools are not always accurate.
Many prostate cancers detected with screening are unlikely to cause death or disability. Thus, a number of men will have to experience the side effects of surgery and radiation for cancers that would never have bothered them had they gone undetected. In other words, even if the screening process works and a cancer is detected, it is not clear in all cases that the treatment is more beneficial than harmful.
PREVENTION OF PROSTATE CANCER
Supplements — Studies suggest that vitamin E and selenium supplements may protect against prostate cancer, but there is not enough evidence to recommend these supplements to all men.
Medications — Finasteride (Proscar®) has been shown to reduce the risk of developing prostate cancer by about 25 percent. However, aggressive cancers were diagnosed more frequently during the first year in men treated with finasteride than in those taking a placebo (look-alike substitute that contains no medication) pill. The reasons for this finding are not clear. It is not clear if finasteride should be offered to men at high risk for prostate cancer.
RECOMMENDATIONS
Professional organizations — Major medical associations and societies have issued conflicting recommendations regarding screening, making it difficult for an individual to decide if screening is right. The United States Preventive Services Task Force [2] and many European cancer societies have not endorsed routine serum PSA screening for the early detection of prostate cancer, while the American Cancer Society [3] and American Urological Association [4] do recommend screening. With currently available data, it is not possible to determine if the benefits of screening outweigh the significant risks associated with treatment.
A number of studies are expected to be completed over the next several years that should help clarify this controversy. In the meantime, the American Cancer Society, American Urological Association, and American College of Physicians recommend that men have an open discussion with their clinician.
The best way to decide if prostate cancer screening is right is to: Consider individual prostate cancer risk factors Know the potential benefits and harms of screening, diagnosis, and treatment Talk to a clinician about concerns or questions.
For men who choose screening — If a man chooses to have screening, he should begin at age 50. Men with risk factors for prostate cancer (such as black men or a man with a father or brother who had prostate cancer) may want to begin screening at the age of 45.
Screening should continue yearly once it is started, though less frequent testing may be appropriate for some men with a low PSA. For men who choose screening, we suggest that those with a PSA level below 1.0 ng/mL consider having PSA testing every four years and that those with a higher PSA level consider having PSA testing annually. We suggest that men who choose screening have an annual digital rectal exam, regardless of their PSA level.
Screening not recommended — Screening should not be performed in men who are 75 years and older or who have serious health problems; these men are unlikely to live long enough to benefit from screening and/or treatment.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.cancer.gov/cancertopics/screening/prostate)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
US TOO! Prostate Cancer Education and Support
(www.ustoo.com/Early_Detection.asp)
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Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Prostate cancer. National Cancer Institute. Web site: http://cancernet.nci.nih.gov/cancertopics/types/prostate.
2. Screening for prostate cancer: recommendation and rationale. Ann Intern Med 2002; 137:915.
3. Smith, RA, von Eschenbach, AC, Wender, R, et al. American Cancer Society Guidelines for the early detection of cancer: update of early detection guidelines for prostate, colorectal, and endometrial cancers. CA Cancer J Clin 2001; 51:38.
4. Prostate-specific antigen (PSA) best practice policy. American Urological Association (AUA). Oncology (Williston Park) 2000; 14:267.
5. Whittemore, AS, Cirillo, PM, Feldman, D, Cohn, BA. Prostate specific antigen levels in young adulthood predict prostate cancer risk: results from a cohort of Black and White Americans. J Urol 2005; 174:872.
6. Carter, HB. Prostate cancers in men with low PSA levels--must we find them?. N Engl J Med 2004; 350:2292.
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