Zanmbeel

Friday, October 12, 2007

Treatment of early stage cervical cancer

INTRODUCTION — More than 10,000 American women develop cancer of the uterine cervix (cervical cancer) each year. Cervical cancer is most frequently diagnosed in women between the ages of 45 and 49. A Pap test (also called cervical cytology screening) involves scraping cells from the cervix and examining them under a microscope; this test can detect abnormal changes in the cells of the cervix before they become cancerous. As a result of the widespread use of Pap tests, the number of women diagnosed with cervical cancer has decreased steadily over the past 50 years. Pre-cancerous lesions are detected far more frequently than invasive cervical cancer. (See "Patient information: Screening for cervical cancer").

Cervical cancer is a treatable condition and there is a good chance of cure if it is found and treated in the early stages. This topic review discusses the diagnosis and treatment of women with early stage cervical cancer. A separate topic review discusses the treatment of early stage cervical cancer in women who want to become pregnant in the future. (See "Patient information: Treatment of early stage cervical cancer for women who desire future pregnancy").

THE CERVIX — The uterus (womb) opens into the vagina through the cervix (show figure 1). The cells on the outermost surface of the cervix are called squamous cells. "Squamous cell carcinoma of the cervix" is the name for cancer that affects these cells. More than 80 percent of cervical cancers are squamous cell carcinomas.

The cervix also includes glandular (also called columnar) cells, which line the opening of the cervix and the canal that leads into the uterus (the endocervical canal) (show picture 1). These cells can also become cancerous; when they do, they are called adenocarcinomas of the cervix. Although they arise from different types of cells, squamous cell carcinoma and adenocarcinoma of the cervix are treated similarly in the early stages.

SIGNS AND SYMPTOMS — Typically, cervical cancers develop slowly over a period of several years. The first step is that the cells of the cervix become abnormal in appearance (called dysplasia). These "precancerous" cells usually cause no signs or symptoms, but can often be detected with a Pap test and treated effectively before they develop into cancer. Therefore, all women who have a cervix should undergo regular screening with Pap tests. (See "Patient information: Screening for cervical cancer").

If a cervical cancer does develop, it may initially not cause any symptoms or it may cause abnormal vaginal discharge or bleeding. This can include bleeding between menstrual periods, bleeding after sexual intercourse, or bleeding after menopause. This bleeding may be no more than a spot of blood.

Abnormal bleeding can also be caused by a number of other conditions that may or may not be related to cancer. Any woman who develops abnormal vaginal bleeding should consult a healthcare provider.

RISK FACTORS — The most important risk factor for cervical cancer is infection with a virus called the human papillomavirus (HPV). 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). HPV can also cause a noncancerous condition called genital warts (condyloma). (See "Patient information: Condyloma (genital warts) in women").

Most HPV infections are temporary because the body's immune system clears the infection. When certain types of HPV virus persist (in 10 to 20 percent of cases), there is a higher likelihood of developing cervical cell abnormalities and cancer. HPV can be detected in almost all cervical cancers (squamous cell carcinomas as well as adenocarcinomas). (See "Patient information: Screening for cervical cancer").

Additional risk factors for cervical cancer include cigarette smoking, and a weakened immune system (caused by certain diseases, medications, and HIV/AIDS).

DIAGNOSIS AND STAGING — Cervical cancer is diagnosed with a cervical biopsy. A biopsy involves removing a small piece of abnormal appearing tissue. This is done either because the clinician sees an abnormal area on the cervix, or because of an abnormal Pap test. The biopsy is performed during an office visit using a procedure called colposcopy. The colposcope (similar to a large magnifying lens) magnifies the cervix (show picture 2). This allows the clinician to better see the location, extent, and degree of very small abnormalities that may not be visible with the naked eye alone.

The tissue obtained during the biopsy is analyzed under a microscope to determine if cancer cells are present. Sometimes the small colposcopy-directed biopsies are not sufficient to diagnose cervical cancer and a larger biopsy, called cervical conization, is needed (show figure 2). If a biopsy shows the presence of a cervical cancer, a doctor who specializes in cancers of the female reproductive system (called a gynecologic oncologist) should be consulted. A gynecologic oncologist has received specialized training in the techniques needed to diagnose and treat cervical as well as other gynecologic cancers.

FIGO staging system — Once a diagnosis of cervical cancer is made, the next step in the evaluation is to assess the "stage" of the cancer. Staging is a system that describes the size of the cancer and any signs of spread. For all cancers, including cervical cancer, treatment and prognosis depend upon the tumor stage. For cervical cancers, the stage is based upon the size of the cancer and how deeply it has invaded into the tissues surrounding the cervix, whether the vagina, side walls of the pelvis, or local lymph nodes are involved, and whether the cancer has spread to other organs (metastasized).

The International Federation of Gynecologists and Obstetricians (FIGO) system is the most commonly used staging system for cervical cancer (show table 1). This system classifies the extent of disease involvement as stage 0 through IV (four), with IV being the most advanced stage [1].

The FIGO staging system is mainly based upon the results of physical examination, which includes a complete pelvic (internal) examination of the cervix, uterus, and ovaries. Other procedures such as cystoscopy (to view the lining of the bladder), proctoscopy (to view the lining of the rectum), and intravenous pyelogram (a radiologic test to evaluate the kidneys, ureters, bladder, and urethra) may also be performed to evaluate how far the cancer has invaded locally. Patients may be asked to undergo a chest x-ray or bone x-rays to detect distant spread to the lungs or bone.

Other imaging tests are often recommended to determine the best treatment approach, but the results do typically not change the FIGO stage. These include computed tomography (CT scan), magnetic resonance imaging (MRI), and/or positron emission tomography (PET scan).

TREATMENT OPTIONS — There are several options for treatment of early stage (stage IA, IB, and some small IIA tumors) cervical cancer. The optimal treatment depends upon the woman's age and her childbearing plans, the stage of the cancer, whether underlying medical conditions are present, and the physician's and patient's preferences.

The most common treatment for early stage cervical cancers is radical hysterectomy (surgical removal of the cervix and uterus). The alternative is radiation therapy, which is usually given in combination with chemotherapy. Patients with the earliest stage cervical cancers (stage IA1) may also be treated by cervical conization or simple hysterectomy alone. (See "Patient information: Treatment of abnormal Pap smears" for information about conization and see "Patient information: Abdominal hysterectomy" for information about simple hysterectomy).

Future pregnancies are not possible after radical hysterectomy or radiation therapy. Some women who wish to preserve their ability to carry a pregnancy after treatment may be eligible for less aggressive forms of treatment (fertility preserving therapies). These involve partial or complete removal of the cervix, while leaving the uterus in place. Women who are not eligible for less aggressive treatment may have options that allow them to have a biologically related child. These issues are discussed separately. (See "Patient information: Treatment of early stage cervical cancer for women who desire future pregnancy").

Radical hysterectomy — Radical hysterectomy is a surgical procedure that removes the uterus and cervix with adjacent tissues and some portion of the vagina (show figure 3). The surgery is done in the operating room after the woman receives anesthesia. Removal of the ovaries is not a necessary part of a radical hysterectomy. A woman's preference to leave or remove the ovaries is usually discussed before surgery. (See "Patient information: Abdominal hysterectomy", section on "Removal of ovaries" for more information about removal of the ovaries).

The surgery is usually performed by removing the uterus and cervix through a vertical or horizontal incision in the abdomen (show figure 3). Alternately, surgery may be done laparoscopically using a small telescope and several small incisions in the abdomen. With laparoscopic surgery, the uterus and cervix are removed through the vagina. The surgical approach depends upon the surgeon's preference and experience and the woman's anatomy. Most women will also undergo a lymphadenectomy (removal of the pelvic and para-aortic lymph nodes, show figure 4), depending upon the stage of the cancer and what is found during surgery.

The time required for radical hysterectomy and pelvic lymphadenectomy is approximately 2.5 to four hours; more time may be required if lymph nodes in other areas are removed or if complications such as bleeding or injury to surrounding organs occurs. Most women remain in the hospital for two to three days after surgery.

If abnormal or cancerous cells are found at the margins (edges) of the tissue or in the lymph nodes that are removed, or if the tumor has other features that increase the risk that the cancer will recur, further (adjuvant) treatment is recommended. This generally includes both radiation therapy and chemotherapy.

Radiation therapy — Radiation therapy (RT) refers to the exposure of a tumor to high-energy x-rays in order to slow or stop its growth. Exposure to x-rays damages cells. Unlike normal cells, cancer cells cannot repair the damage caused by exposure to x-rays, particularly when it is administered over several days. This prevents the cells from further growth, and causes them to eventually die.

There are two ways to deliver RT for cervical cancer: brachytherapy or external beam radiation therapy (EBRT).

Brachytherapy — Brachytherapy is a form of localized RT in which the source of the radiation is within the patient (internal irradiation). This allows the delivery of high doses of radiation to the area where cancer cells are most likely to be found, hopefully minimizing the effects of radiation on healthy tissues.

In most cases, a radiation applicator is temporarily inserted through the vagina into the cervix and uterus. Then, the radiation source is placed (or "afterloaded") into the applicator and left in place internally for a period of time. The treatment is traditionally accomplished using a radiation source that delivers the radiation at a low dose rate (LDR), which requires that the woman remain in the hospital for two to three nights. A newer technique delivers the radiation at a high dose rate (HDR). The main advantage of HDR is that it is completed within several minutes, and can be performed as an outpatient. Studies that compare HDR to LDR therapy are ongoing.

External beam radiation therapy (EBRT) — During EBRT, the radiation beam is generated by a machine that is outside the patient. The radiation is delivered to the patient, who is usually lying on a table underneath or in front of the machine. The high energy beams are targeted to the pelvic area.

Exposure to the beam typically takes only a few seconds (similar to having an x-ray). In general, treatment is repeated five days per week for approximately five to six weeks. Treatment cannot be given over a shorter period because the higher daily doses would cause too many side effects. Unless medically indicated, treatment should not be interrupted or extended beyond the projected time frame because changing the schedule or stopping temporarily could reduce the chance of curing the cancer.

Brachytherapy alone is adequate treatment for the earliest stage IA tumors, but EBRT is generally added to brachytherapy to improve the outcomes in women who have with more advanced disease [2].

Chemotherapy — Most women who undergo EBRT for cervical cancer also receive chemotherapy during the radiation therapy (an approach termed chemoradiotherapy). Chemotherapy drugs are medicines that stop or slow the growth of cancer cells. In general, these drugs work by interfering with the ability of rapidly growing cells (like cancer cells) to divide or multiply. Chemotherapy also has the ability to enhance the damaging effect of radiation therapy on cancer cells; when chemotherapy drugs are used in this manner, they are referred to as "radiation sensitizers". The chemotherapy is usually given once per week through a vein during the course of EBRT.

It is not clear if there is a benefit of chemoradiotherapy (compared to radiotherapy alone) for all women with early stage disease. Studies of women with predominantly locally advanced cervical cancer have demonstrated that there is a lower risk of recurrence and a better survival when RT is given along with chemotherapy compared to when RT is given alone [3]. That benefit was greater in trials that included a higher proportion of patients with stage I and II disease [4]. It has not been proven that these results apply to women with smaller early stage tumors, although most gynecologic oncologists recommend that chemotherapy be administered when EBRT is used for definitive therapy, regardless of the stage.

FOLLOW UP — After cervical cancer treatment, periodic follow-up testing and examination are recommended. Guidelines from the National Comprehensive Cancer Network (NCCN) suggest the following [6]: Physical examination every three months for one year, every four months for one year, every six months for three years, and then annually. This usually involves a physical examination and Pap test (cervical cytology). Annual chest x-ray; there are few data to support the benefit of annual chest x-rays and many doctors do not recommend them. Other radiographic studies, including CT or PET scan, are recommended as clinically indicated

LONG-TERM OUTLOOK

Psychosocial function — The women and families affected by cervical cancer commonly experience distress as they worry about their short and long-term health and risk of recurrence. In some cases, this distress continues for many years after treatment ends.

Communication between the woman, her family, and her healthcare team is a vital part of the treatment process. Many women benefit from bringing a family member or friend to physician visits; this person can help the woman to understand her options, ask important questions, take notes, and feel supported.

A variety of support options are available, both during and following treatment, including individual counseling, support groups, and internet-based discussion groups. A list of reputable groups is available below (see "Where to get more information" below).

Sexual function — Vaginal changes after cervical cancer treatment may include shortening, narrowing, and decreased lubrication. These physical changes impact sexual satisfaction because they may result in pain during intercourse, lack of interest in sex, difficulty having an orgasm, and decreased frequency of sexual activity. If the vagina is severely narrowed, use of vaginal dilators may help.

Using a vaginal moisturizer or lubricant during intercourse can relieve some of these bothersome symptoms. Counseling for sexual and/or psychological difficulties may also be helpful. (See "Patient information: Sexual problems in women").

Cure — Each patient with cancer is different, and it is difficult to predict what an individual woman can expect in the future. The chance of cure is high for most early stage cervical cancers. When discussing chances of cure, it is important to remember that these numbers represent averages, and do not necessarily predict what will happen to you.

The survival rates for women who undergo standard treatment for stage IA1 cervical cancer are excellent. At five years after diagnosis, more than 98 percent of women are alive. This means that 2 percent of women died, although the cause of death was not necessarily related to the cancer.

For stage IA2, more than 95 percent of women who undergo standard treatment are alive at five years after diagnosis. For stage IB1 disease, approximately 88 percent of women are alive at five years after diagnosis. Again, some of these women died as a result of their cancer, while others died of other causes (eg, accidents, heart disease).

CLINICAL TRIALS — Progress in treating cervical cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

www.cancer.gov/clinical_trials/learning/
www.cancer.gov/clinical_trials/
http://clinicaltrials.gov/

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. People Living With Cancer: The official patient information

website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
The Gynecologic Cancer Foundation

(www.sgo.org/publications/gynecologic_cancer.cfm)
National Comprehensive Cancer Network

(www.nccn.org/patients/patient_gls.asp)
Gynecologic Oncology Group

(www.gog.org/gynecologiccancerinformation.html)
National Cancer Institute

1-800-4-CANCER
(www.cancer.gov/)
American Cancer Society

1-800-ACS-2345
(www.cancer.org)
The National Cervical Cancer Coalition

(www.ncc-online.org)

[1-7]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Benedet, JL, Bender, H, Jones H, 3rd, et al. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet 2000; 70:209.
2. Nag, S, Chao, C, Erickson, B, et al. The American Brachytherapy Society recommendations for low-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 2002; 52:33.
3. Green, J, Kirwan, J, Tierney, J, et al. Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix. Cochrane Database Syst Rev 2005; :CD002225.
4. Keys, HM, Bundy, BN, Stehman, FB, et al. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 1999; 340:1154.
5. Rotman, M, Sedlis, A, Piedmonte, MR, et al. A phase III randomized trial of postoperative pelvic irradiation in Stage IB cervical carcinoma with poor prognostic features: follow-up of a gynecologic oncology group study. Int J Radiat Oncol Biol Phys 2006; 65:169.
6. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology available at www.nccn.org/professionals/physician_gls/default.asp (Accessed February 5, 2007).
7. ACOG practice bulletin. Diagnosis and treatment of cervical carcinomas. Number 35, May 2002. American College of Obstetricians and Gynecologists. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 2002; 78:79.

Treatment of abnormal Pap smears

INTRODUCTION — Several treatments are available for women with cervical abnormalities, often referred to as dysplasia, CIN (cervical intraepithelial neoplasia) or CIS (carcinoma in situ). Treatments including cryosurgery (freezing), laser (high-energy light), and excision (surgical removal of the abnormal area).

A separate topic review discusses the testing used to diagnose these types of cervical abnormalities, including Pap smears or ThinPrep cytology, human papillomavirus (HPV) testing, and colposcopy. (See "Patient information: Screening for cervical cancer").

CHOOSING THE BEST TREATMENT — Abnormal pap smears are treated by identifying the area of abnormal cervical tissue and removing it to prevent worsening or spread to other areas of the cervix. There are two main types of treatment for cervical abnormalities: those that destroy the abnormal area (called ablative therapy) and those that remove the abnormal areas (called excisional therapy). Some abnormalities are best treated with one type of treatment while others can be treated with either type, depending upon the patient and physician's preference. There are some classes of abnormalities that can be followed without treatment, if the physician and patient are willing.

Excisional therapy — Excisional therapies include loop electrosurgical excision procedures (LEEP, also called large loop excision of the transformation zone (LLETZ), laser conization, and cervical conization procedures. Most clinicians prefer excisional therapy (see "Excision" below).

Excisional therapy is recommended when the extent or type of cervical abnormality is not clear based upon colposcopy and biopsy. In this situation, excision is preferred because the abnormal tissue can be examined with a microscope. This allows the physician to determine if the entire abnormal area was removed and if a more serious condition (eg, cervical cancer) is present.

Ablative therapy — Ablative therapies include cryosurgery and laser ablation. Ablative therapy may be recommended when there is less concern about cancer or about the extent of the abnormal tissue.

EXCISION — Excision is a procedure that cuts out the abnormal area on the surface of the cervix; excision can also remove abnormalities that extend inside the cervical opening. A table that compared the different techniques is provided (show table 1). Excision serves two purposes: It provides a sample of tissue to confirm the degree of an abnormality and check for cancerous or precancerous cells deep within the cervix. Excision helps to ensure that the abnormality is removed completely. If the edges of the tissue that is removed show evidence of the abnormality or precancer, further treatment may be needed.

Loop electrosurgical excision procedure (LEEP) — Excision can be done with a device that uses electrical current; this is called a LEEP procedure (loop electrosurgical excision procedure) or LLETZ (large loop excision of the transformation zone) (show table 1). A thin, wire loop is inserted through the vagina (show figure 1), where it uses an electric current to remove a cone-shaped portion of the cervix (show figure 2). This can also be performed with a laser knife, which uses high intensity energy from a light beam.

Excision can be done in the office or operating room after the cervix is injected with local anesthesia to prevent pain. The woman may feel a dull ache or cramp during the procedure. A brown paste is applied after the treatment to prevent bleeding; this often causes a dark vaginal discharge (similar to coffee grounds). Most women are able to return to work or school after the procedure.

Cervical cone biopsy (conization) — Excision can also be done with a scalpel instead of a loop; this is called a cervical conization or cone biopsy (show figure 3). Conization is usually done in an operating room after the patient has received general anesthesia (medicine given to induce sleep) or regional anesthesia (eg, epidural or spinal) (show table 1).

Following LEEP or conization, most women have mild to moderate vaginal bleeding and discharge for one to two weeks. The bleeding should not be heavy (eg, should not soak a pad in less than one hour). Care after excision is described below (see "Post-procedure care" below).

Complications — As with any surgical procedure, complications can occur during excision. These include: Bleeding during the procedure — Bleeding is rarely serious, and can usually be managed with suturing or by applying cauterizing material (a liquid or treatment that helps the blood to clot) to the cervix. Perforation of the uterus — This is an uncommon complication, and is more likely to occur in women who are postmenopausal or whose uterus is tipped forward. If the uterus is perforated it usually heals without any need for treatment. Infrequently, laparoscopy or laparotomy are required to see and repair injuries to internal organs. Bleeding after the procedure — Although light bleeding or spotting is normal, some women have heavy bleeding several days or weeks after the procedure. This can usually be treated in the office, but occasionally a procedure in an operating room is necessary. Infection — Infections occur rarely after cone biopsy, either on the cervix itself or elsewhere in the reproductive tract. Most infections can be treated with oral antibiotic therapy. Late complications — See "Pregnancy after treatment" below.

ABLATIVE TREATMENTS — Ablative treatment destroy, rather then cut away, abnormal cervical tissue.

Cryosurgery — Cryosurgery involves applying liquid nitrogen or carbon dioxide to the cervix. This causes the cervical tissue to freeze, which destroys the abnormal cells. Cryosurgery can be done in the office, similar to a pelvic examination, without any anesthesia. It may cause mild cramping or discomfort.

Cryosurgery is not recommended in certain situations, such as when the extent and type of cervical abnormality are not clear based upon colposcopy and/or biopsy. Excisional therapy is preferred in these cases.

Most women have watery vaginal discharge for one week after cryosurgery. Care after cryosurgery is described below (see "Post-procedure care" below).

Laser ablation — Laser ablation uses high intensity energy from a light beam to destroy abnormal areas of the cervix. The laser is directed to the abnormal area of the cervix through the vagina. This is usually performed in an operating room after the woman has received general anesthesia (medicine given to induce sleep) or regional anesthesia (eg, epidural or spinal). Laser treatment requires special training and equipment.

A disadvantage of laser ablation is that it destroys the abnormal tissue, similar to cryosurgery. Laser ablation is not recommended in certain situations, such as when the extent and type of cervical abnormality are not clear based upon colposcopy and/or biopsy.

Most women have vaginal discharge for one to two weeks after laser treatment. Care after laser treatment is described below (see "Post-procedure care" below).

POST-PROCEDURE CARE — All women should ask about their ability to drive home from the procedure and when they can resume normal daily activities. Following treatment, most providers recommend avoiding sexual intercourse, not placing anything in the vagina (eg, douches, tampons), and not taking a bath or swim for a few weeks (showers are fine); other physicians may recommend a shorter period of "pelvic rest." This should be discussed in detail with the physician.

In general, a woman should call her provider if she has bleeding that is heavier than a normal menstrual period (defined as soaking a pad in less than one hour, especially if there are clots), severe or worsening pain, fever over 101º F (38.4º C), or a foul-smelling vaginal discharge.

Treatment efficacy — The treatments described above cure most women with abnormal cervical cells. Women that are not cured after a first treatment may have persistence, recurrence, or progression of the abnormality, especially if a high risk type of HPV (types 16 and 18) is present. Additional treatment is sometimes needed in this case. For this reason, lifelong follow up with cervical cytology smears (Pap smear or ThinPrep) is important.

Follow up appointments — Typically, a woman is seen for a follow up examination several weeks after treatment to make sure the cervix is healing. A Pap smear (with or without colposcopy) is recommended approximately every six months. Colposcopy is recommended if atypical squamous cells or other abnormalities are found and HPV testing is positive. The time interval between subsequent tests will depend upon the results of the initial testing after treatment and the woman's age. Follow up is best discussed with a woman's individual provider since it may vary significantly from one woman to another.

Need for further treatment — Some women will require additional treatments to ensure that all abnormal areas are removed. This is especially true if excision was done and microscopic analysis showed a larger abnormality than was expected. The decision to have additional treatment is individualized, based upon the type of abnormality seen, the woman's risk of cervical cancer, and whether or not childbearing is completed. (See "Patient information: Treatment of early stage cervical cancer").

PREGNANCY AFTER TREATMENT — Many women are concerned about the risks of infertility and preterm labor after being treated for an abnormal Pap smear. The risk of these complications depends upon a number of factors, including the type and number of treatment(s) performed (ablation versus excision) and the time between the treatment and the pregnancy. In addition, other factors, such as underlying medical conditions and a woman's age, can increase a woman's risk of these conditions.

Most women are advised to wait six to 12 months after conization before attempting to become pregnant to allow the tissue to heal fully. In general, the data suggest that excisional procedures slightly increase the risk of preterm delivery, but ablative procedures do not. The risk of infertility related to treatment is probably very small. More data are needed to define these risks better. (See "Patient information: Preterm labor", section on cervical length)".

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 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)
Center for Disease Control and Prevention

(www.cdc.gov/)
American Social Health Association

(http://www.ashastd.org/)

[1-5]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Martin-Hirsch, PL, Paraskevaidis, E, Kitchener, H. Surgery for cervical intraepithelial neoplasia. Cochrane Database Syst Rev 2000; :CD001318.
2. Matseoane, S, Williams, SB, Navarro, C, et al. Diagnostic value of conization of the uterine cervix in the management of cervical neoplasia: a review of 756 consecutive patients. Gynecol Oncol 1992; 47:287.
3. Gok, M, Coupe, VM, Berkhof, J, et al. HPV16 and increased risk of recurrence after treatment for CIN. Gynecol Oncol 2007; 104:273.
4. Kalliala, I, Anttila, A, Pukkala, E, Nieminen, P. Risk of cervical and other cancers after treatment of cervical intraepithelial neoplasia: retrospective cohort study. BMJ 2005; 331:1183.
5. Kyrgiou, M, Koliopoulos, G, Martin-Hirsch, P, et al. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet 2006; 367:489.

Treatment of abnormal Pap smears

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.

Screening for cervical cancer

Screening for colon cancer

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.

Pages

Friday, October 12, 2007

Treatment of early stage cervical cancer

Treatment of abnormal Pap smears

Treatment of abnormal Pap smears

Screening for cervical cancer

Screening for cervical cancer

Screening for colon cancer