Colon polyps

THE SIGNIFICANCE OF POLYPS — The presence of polyps in the colon or rectum often raises questions for patients and their family. What is the significance of finding a polyp? Does this mean that I have, or will develop, colon or rectal (colorectal) cancer? Will a polyp require surgery?

Some types of polyps (called adenomas) have the potential to become cancerous while others (hyperplastic or inflammatory polyps) have virtually no chance of becoming cancerous.

When discussing colon polyps, the following points should be considered: Polyps are common (they occur in 30-50 percent of adults) Not all polyps will become cancer It takes many years for a polyp become cancerous Polyps can be completely and safely removed

The best course of action when a polyp is found depends upon the type, size, and location of the polyps and the way in which they were removed. Most people who have an adenoma removed will require a follow up examination; this allows the clinician to be sure that all adenomas have been removed.

CAUSES — Polyps are very common in men and women of all races who live in industrialized countries, which suggests that dietary and environmental factors are important in their development.

Lifestyle — Although the exact causes are not completely understood, lifestyle risk factors include the following: A high fat diet A diet high in red meat A low fiber diet Cigarette smoking Obesity

On the other hand, use of aspirin and other NSAIDs and calcium intake may protect against the development of colon cancer. (See "Patient information: Screening for colon cancer").

Aging — Colorectal cancer is uncommon before age 40. Ninety percent of cases occur after age 50, with men and women being equally affected; therefore, colon cancer screening usually begins at age 50 for both sexes. It takes approximately 10 years for a small polyp to grow and develop into cancer.

Family history and genetics — Polyps and colon cancer tend to run in families, which suggests that genetic factors are also important in their development. Research on the genetic basis of colon cancer is ongoing.

Any history of colon polyps or colon cancer in the family should be discussed with a healthcare provider, particularly if cancer developed at an early age, in close relatives, or in multiple family members. As a general rule, screening for colon cancer begins at an earlier age in people with a family history of cancer or polyps.

Rare genetic diseases can cause high rates of colorectal cancer relatively early in adult life. One disease that causes multiple colon polyps is familial adenomatous polyposis (FAP). Hereditary Non-Polyposis Colon Cancer (HNPCC) also significantly increases the risk of colon cancer, often beginning in the 20s and 30s, but does not cause a large number of polyps. Testing for these genes may be recommended for families with high rates of colorectal cancer, but is not generally recommended for other groups.

TYPES OF POLYPS — The two most common types of polyps are hyperplastic and adenomatous polyps. Other types of polyps can also be found in the colon, although these are far less common and are not discussed here.

Hyperplastic polyps — Hyperplastic polyps are usually small, located in the end-portion of the colon (the rectum and sigmoid colon), have no potential to become malignant, and are not concerning (show figure 1). It is not always possible to distinguish a hyperplastic polyp from an adenomatous polyp based upon appearance, which means that hyperplastic polyps are often removed or biopsied to allow microscopic examination.

Adenomatous polyps — Two-thirds of colon polyps are adenomas. Most of these polyps do not develop into cancer, although they have the potential to become cancerous. Adenomas are classified by their size, general appearance, and their specific features as seen under the microscope.

As a general rule, the larger the adenoma, the more likely it is to eventually become a cancer; large adenomas may already contain cancer cells. As a result, large polyps are usually biopsied (a small sample of tissue is removed) or removed completely to allow for microscopic examination.

DIAGNOSIS — Polyps usually do not cause symptoms. They are most commonly detected during a colon cancer screening examinations (such as flexible sigmoidoscopy or colonoscopy, show endoscopy 1) or during testing after a positive stool blood test. Polyps can also be detected on a barium enema x-ray, although small polyps are less often seen on x-ray and cannot be removed during the examination.

Colonoscopy is the best way to evaluate the colon because it allows the physician to see the entire lining of the colon and remove any polyps that are found. During colonoscopy, a physician inserts a very thin flexible tube with a light source and small camera into the anus. The tube is advanced through the entire length of the large intestine (colon). (See "Patient information: Colonoscopy").

The inside of the colon is a tube-like structure with a flat surface with curved folds. A polyp appears as a lump that protrudes into the inside of the colon (show endoscopy 1). The tissue covering a polyp may look the same as normal colon tissue, or, there may be tissue changes ranging from subtle color changes to ulceration and bleeding. Some polyps are flat ("sessile") and others extend out on a stalk ("pedunculated").

Colonoscopy is also the best test for the follow-up examination of polyps. New technologies are being developed that show promise for detecting polyps (including molecular genetic tests and "virtual colonoscopy" using CT or MRI technology). Further study is needed before these tests are recommended to the general public.

POLYP REMOVAL — Colorectal cancer is the second leading cause of cancer deaths in the United States, accounting for 14 percent of cancer deaths. Colorectal cancer is preventable if precancerous polyps (ie, adenomas) are detected and removed before they become malignant (cancerous). Over time, small polyps can change their structure and become cancerous. Polyps are removed when they are found on colonoscopy, which eliminates the potential for them to become malignant.

Procedure — The medical term for removing polyps is polypectomy. Most polypectomies can be performed through a colonoscope. Small polyps can be removed with an instrument that is inserted through the colonoscope and snips off small pieces of tissue (show endoscopy 2). Larger polyps are usually removed by placing a noose, or snare, around the polyp base and burning through it with electric cautery (show endoscopy 3). The cautery also helps to stop bleeding after the polyp is removed.

Polyp removal is not painful because the colon does not have the ability to feel pain. In addition, a sedative medication is given before the colonoscopy to prevent pain and induce sleep. Rarely, a polyp will be too large to remove during colonoscopy, which means that a surgical procedure will be needed at a later time.

Complications — Polypectomy is very safe, but it has a few risks and potential complications. The most common complications of polypectomy include bleeding and perforation (creating a hole in the colon). Fortunately, this occurs infrequently (one in a thousand patients having colonoscopy). Bleeding can usually be controlled during colonoscopy by cauterizing (applying heat) to the bleeding site; surgery is sometimes required for perforation.

After polyp removal — Medications that can increase bleeding, including aspirin, ibuprofen (Advil®, Motrin®), and naproxen (Aleve®), should be avoided for two weeks after polypectomy. Acetaminophen (Tylenol®) is safe to take. People who require anticoagulant medications such as warfarin (Coumadin®) should discuss how and when to resume this medication after polypectomy with their clinician.

A follow up appointment or phone call is usually scheduled after the polyp removal to discuss the results of the tissue analysis and the need for a repeat examination.

PREVENTION

Follow up examination — People with adenomatous polyps have an increased risk of developing more polyps, which are likely to be adenomatous. There is a 25 to 30 percent chance that adenomas will be present on a repeat colonoscopy done three years after initial polypectomy. Some of these polyps may have been present during the original examination, but were too small to detect. Other new polyps may also have developed.

After polyps are removed, repeat colonoscopy is recommended, usually three to five years after the initial colonoscopy. However, this time interval depends upon several factors: Characteristics of the polyps when they are analyzed under the microscope Number and size of the polyps The appearance of the colon during the colonoscopy. A bowel preparation is needed before colonoscopy to remove all traces of feces (stool). If the bowel prep was not completed, feces may remain in the colon, making it more difficult to see small to moderate size polyps. In this situation, follow up colonoscopy may be recommended sooner than three to five years later.

Persons who undergo screening (and re-screening) for colon cancer are much less likely to die from colon cancer. Thus, following screening guidelines is one of the most important measures.

Preventing colon cancer — Intensive research is underway to develop ways to prevent polyps and colon cancer with diet or with medications. A number of nutrients and medications have been identified that may reduce the risk of colon cancer. Guidelines issued by one of the major medical societies in the United States (the American College of Gastroenterology) suggest the following to prevent polyps from recurring: Eat a diet that is low in fat and high in fruits, vegetables, and fiber Maintain a normal body weight Avoid smoking and excessive alcohol use Consider taking a dietary supplementation with 3 g of calcium carbonate

(See "Patient information: Diet and health" and see "Patient information: Smoking cessation").

IMPLICATIONS FOR THE FAMILY — First-degree relatives (a parent, brother, sister, or child) of a person who has been diagnosed with an adenomatous polyp (or colorectal cancer) before the age of 60 years are at increased risk for adenomatous polyps and colorectal cancer compared to the general population. Thus, family members should be made aware if adenoma or colon cancer are diagnosed. While screening for polyps and cancer is recommended for all people at risk (typically beginning at age 50), those at increased risk should begin screening earlier, typically at age 40.

Relatives can be told the following: People who have one first-degree relative (parent, brother, sister, or child) with 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. Screening should be repeated every five years. People who have one first-degree relative (parent, brother, sister, or child) with colorectal cancer or adenomatous polyps at age 60 or later should begin screening at age 40, and screening should be repeated similar to a person with an average risk of colon cancer. (See "Patient information: Screening for colon cancer" section on "Average risk"). People with a second-degree relative (grandparent, aunt, or uncle) or third-degree relative (great-grandparent or cousin) with colorectal cancer may be screened similar to a person with an average risk. (See "Patient information: Screening for colon cancer" section on "Average risk").

Some conditions, such as hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, and inflammatory bowel disease (eg, ulcerative colitis, Crohn's disease) significant increase the risk of colonic polyps or cancer in family members. Colon cancer screening in this group is discussed separately. (See "Patient information: Screening for colon cancer" section on "Increased risk").

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)
The American Gastroenterological Association

(www.gastro.org)
The American College of Gastroenterology

(www.acg.gi.org)
The American Society of Colon and Rectal Surgeon

(www.fascrs.org)


[1-3]


Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Winawer, S, Fletcher, R, Rex, D, et al. Colorectal cancer screening. Gastroenterology 2003; 124:544.
2. Winawer, SJ, Zauber, AG, Ho, MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med 1993; 329:1977.
3. Bond, JH. Polyp guideline: Diagnosis, treatment, and surveillance for patients with colorectal polyps. Am J Gastroenterol 2000; 95:3053.

Colon polyps

THE SIGNIFICANCE OF POLYPS — The presence of polyps in the colon or rectum often raises questions for patients and their family. What is the significance of finding a polyp? Does this mean that I have, or will develop, colon or rectal (colorectal) cancer? Will a polyp require surgery?

Some types of polyps (called adenomas) have the potential to become cancerous while others (hyperplastic or inflammatory polyps) have virtually no chance of becoming cancerous.

When discussing colon polyps, the following points should be considered: Polyps are common (they occur in 30-50 percent of adults) Not all polyps will become cancer It takes many years for a polyp become cancerous Polyps can be completely and safely removed

The best course of action when a polyp is found depends upon the type, size, and location of the polyps and the way in which they were removed. Most people who have an adenoma removed will require a follow up examination; this allows the clinician to be sure that all adenomas have been removed.

CAUSES — Polyps are very common in men and women of all races who live in industrialized countries, which suggests that dietary and environmental factors are important in their development.

Lifestyle — Although the exact causes are not completely understood, lifestyle risk factors include the following: A high fat diet A diet high in red meat A low fiber diet Cigarette smoking Obesity

On the other hand, use of aspirin and other NSAIDs and calcium intake may protect against the development of colon cancer. (See "Patient information: Screening for colon cancer").

Aging — Colorectal cancer is uncommon before age 40. Ninety percent of cases occur after age 50, with men and women being equally affected; therefore, colon cancer screening usually begins at age 50 for both sexes. It takes approximately 10 years for a small polyp to grow and develop into cancer.

Family history and genetics — Polyps and colon cancer tend to run in families, which suggests that genetic factors are also important in their development. Research on the genetic basis of colon cancer is ongoing.

Any history of colon polyps or colon cancer in the family should be discussed with a healthcare provider, particularly if cancer developed at an early age, in close relatives, or in multiple family members. As a general rule, screening for colon cancer begins at an earlier age in people with a family history of cancer or polyps.

Rare genetic diseases can cause high rates of colorectal cancer relatively early in adult life. One disease that causes multiple colon polyps is familial adenomatous polyposis (FAP). Hereditary Non-Polyposis Colon Cancer (HNPCC) also significantly increases the risk of colon cancer, often beginning in the 20s and 30s, but does not cause a large number of polyps. Testing for these genes may be recommended for families with high rates of colorectal cancer, but is not generally recommended for other groups.

TYPES OF POLYPS — The two most common types of polyps are hyperplastic and adenomatous polyps. Other types of polyps can also be found in the colon, although these are far less common and are not discussed here.

Hyperplastic polyps — Hyperplastic polyps are usually small, located in the end-portion of the colon (the rectum and sigmoid colon), have no potential to become malignant, and are not concerning (show figure 1). It is not always possible to distinguish a hyperplastic polyp from an adenomatous polyp based upon appearance, which means that hyperplastic polyps are often removed or biopsied to allow microscopic examination.

Adenomatous polyps — Two-thirds of colon polyps are adenomas. Most of these polyps do not develop into cancer, although they have the potential to become cancerous. Adenomas are classified by their size, general appearance, and their specific features as seen under the microscope.

As a general rule, the larger the adenoma, the more likely it is to eventually become a cancer; large adenomas may already contain cancer cells. As a result, large polyps are usually biopsied (a small sample of tissue is removed) or removed completely to allow for microscopic examination.

DIAGNOSIS — Polyps usually do not cause symptoms. They are most commonly detected during a colon cancer screening examinations (such as flexible sigmoidoscopy or colonoscopy, show endoscopy 1) or during testing after a positive stool blood test. Polyps can also be detected on a barium enema x-ray, although small polyps are less often seen on x-ray and cannot be removed during the examination.

Colonoscopy is the best way to evaluate the colon because it allows the physician to see the entire lining of the colon and remove any polyps that are found. During colonoscopy, a physician inserts a very thin flexible tube with a light source and small camera into the anus. The tube is advanced through the entire length of the large intestine (colon). (See "Patient information: Colonoscopy").

The inside of the colon is a tube-like structure with a flat surface with curved folds. A polyp appears as a lump that protrudes into the inside of the colon (show endoscopy 1). The tissue covering a polyp may look the same as normal colon tissue, or, there may be tissue changes ranging from subtle color changes to ulceration and bleeding. Some polyps are flat ("sessile") and others extend out on a stalk ("pedunculated").

Colonoscopy is also the best test for the follow-up examination of polyps. New technologies are being developed that show promise for detecting polyps (including molecular genetic tests and "virtual colonoscopy" using CT or MRI technology). Further study is needed before these tests are recommended to the general public.

POLYP REMOVAL — Colorectal cancer is the second leading cause of cancer deaths in the United States, accounting for 14 percent of cancer deaths. Colorectal cancer is preventable if precancerous polyps (ie, adenomas) are detected and removed before they become malignant (cancerous). Over time, small polyps can change their structure and become cancerous. Polyps are removed when they are found on colonoscopy, which eliminates the potential for them to become malignant.

Procedure — The medical term for removing polyps is polypectomy. Most polypectomies can be performed through a colonoscope. Small polyps can be removed with an instrument that is inserted through the colonoscope and snips off small pieces of tissue (show endoscopy 2). Larger polyps are usually removed by placing a noose, or snare, around the polyp base and burning through it with electric cautery (show endoscopy 3). The cautery also helps to stop bleeding after the polyp is removed.

Polyp removal is not painful because the colon does not have the ability to feel pain. In addition, a sedative medication is given before the colonoscopy to prevent pain and induce sleep. Rarely, a polyp will be too large to remove during colonoscopy, which means that a surgical procedure will be needed at a later time.

Complications — Polypectomy is very safe, but it has a few risks and potential complications. The most common complications of polypectomy include bleeding and perforation (creating a hole in the colon). Fortunately, this occurs infrequently (one in a thousand patients having colonoscopy). Bleeding can usually be controlled during colonoscopy by cauterizing (applying heat) to the bleeding site; surgery is sometimes required for perforation.

After polyp removal — Medications that can increase bleeding, including aspirin, ibuprofen (Advil®, Motrin®), and naproxen (Aleve®), should be avoided for two weeks after polypectomy. Acetaminophen (Tylenol®) is safe to take. People who require anticoagulant medications such as warfarin (Coumadin®) should discuss how and when to resume this medication after polypectomy with their clinician.

A follow up appointment or phone call is usually scheduled after the polyp removal to discuss the results of the tissue analysis and the need for a repeat examination.

PREVENTION

Follow up examination — People with adenomatous polyps have an increased risk of developing more polyps, which are likely to be adenomatous. There is a 25 to 30 percent chance that adenomas will be present on a repeat colonoscopy done three years after initial polypectomy. Some of these polyps may have been present during the original examination, but were too small to detect. Other new polyps may also have developed.

After polyps are removed, repeat colonoscopy is recommended, usually three to five years after the initial colonoscopy. However, this time interval depends upon several factors: Characteristics of the polyps when they are analyzed under the microscope Number and size of the polyps The appearance of the colon during the colonoscopy. A bowel preparation is needed before colonoscopy to remove all traces of feces (stool). If the bowel prep was not completed, feces may remain in the colon, making it more difficult to see small to moderate size polyps. In this situation, follow up colonoscopy may be recommended sooner than three to five years later.

Persons who undergo screening (and re-screening) for colon cancer are much less likely to die from colon cancer. Thus, following screening guidelines is one of the most important measures.

Preventing colon cancer — Intensive research is underway to develop ways to prevent polyps and colon cancer with diet or with medications. A number of nutrients and medications have been identified that may reduce the risk of colon cancer. Guidelines issued by one of the major medical societies in the United States (the American College of Gastroenterology) suggest the following to prevent polyps from recurring: Eat a diet that is low in fat and high in fruits, vegetables, and fiber Maintain a normal body weight Avoid smoking and excessive alcohol use Consider taking a dietary supplementation with 3 g of calcium carbonate

(See "Patient information: Diet and health" and see "Patient information: Smoking cessation").

IMPLICATIONS FOR THE FAMILY — First-degree relatives (a parent, brother, sister, or child) of a person who has been diagnosed with an adenomatous polyp (or colorectal cancer) before the age of 60 years are at increased risk for adenomatous polyps and colorectal cancer compared to the general population. Thus, family members should be made aware if adenoma or colon cancer are diagnosed. While screening for polyps and cancer is recommended for all people at risk (typically beginning at age 50), those at increased risk should begin screening earlier, typically at age 40.

Relatives can be told the following: People who have one first-degree relative (parent, brother, sister, or child) with 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. Screening should be repeated every five years. People who have one first-degree relative (parent, brother, sister, or child) with colorectal cancer or adenomatous polyps at age 60 or later should begin screening at age 40, and screening should be repeated similar to a person with an average risk of colon cancer. (See "Patient information: Screening for colon cancer" section on "Average risk"). People with a second-degree relative (grandparent, aunt, or uncle) or third-degree relative (great-grandparent or cousin) with colorectal cancer may be screened similar to a person with an average risk. (See "Patient information: Screening for colon cancer" section on "Average risk").

Some conditions, such as hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, and inflammatory bowel disease (eg, ulcerative colitis, Crohn's disease) significant increase the risk of colonic polyps or cancer in family members. Colon cancer screening in this group is discussed separately. (See "Patient information: Screening for colon cancer" section on "Increased risk").

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)
The American Gastroenterological Association

(www.gastro.org)
The American College of Gastroenterology

(www.acg.gi.org)
The American Society of Colon and Rectal Surgeon

(www.fascrs.org)


[1-3]


Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Winawer, S, Fletcher, R, Rex, D, et al. Colorectal cancer screening. Gastroenterology 2003; 124:544.
2. Winawer, SJ, Zauber, AG, Ho, MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med 1993; 329:1977.
3. Bond, JH. Polyp guideline: Diagnosis, treatment, and surveillance for patients with colorectal polyps. Am J Gastroenterol 2000; 95:3053.

Treatment of early stage cervical cancer for women who desire future pregnancy

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 the earliest stages of localized cervical cancer who wish to preserve their ability to become pregnant in the future. A separate topic review discusses the standard treatment of all early stage cervical cancers (which usually includes hysterectomy). (See "Patient information: Treatment of early stage cervical cancer").

THE CERVIX — The uterus (womb) opens into the vagina through the cervix (show figure 1). Squamous cells make up the outer layer of the cervix. Squamous cell carcinoma of the cervix is the name for cancer that affects these cells.

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 a cancer. Therefore, all women who have a cervix should have regular screening with Pap tests. (See "Patient information: Screening for cervical cancer").

If a cervical cancer does develop, it may initially cause no 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 vaginal 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 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 infection can also cause a noncancerous condition called condyloma (genital warts). (See "Patient information: Condyloma (genital warts) in women").

Most HPV infections are temporary because the body's immune system effectively clears the infection. When certain types of the HPV virus persist in the body, there is a higher likelihood that the viral infection will cause cervical cell abnormalities such as dysplasia or cancer; persistent infections are believed to occur in 10 to 20 percent of women. Evidence of HPV infection can be detected in almost all cervical cancers (squamous cell carcinomas as well as adenocarcinomas). For more information about HPV testing, 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, or 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. If a biopsy shows the presence of a cervical cancer, the woman should consult with a doctor who specializes in cancers of the female reproductive system (called a gynecologic oncologist). 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 (metastasis).

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 an 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 — Early stage cervical cancer refers to stage IA, IB, and some small IIA tumors (show table 1). There are several options for treatment of these women. The optimal choice depends upon the stage, the estimated risk of a cancer recurrence following treatment, the woman's age and plans for future pregnancy, whether underlying medical conditions are present, and the preferences of the patient and her physician.

Radical hysterectomy — For women with early stage cervical cancer who do not plan pregnancy in the future, a radical hysterectomy (surgical removal of the uterus, cervix and upper part of the vagina) is the standard treatment. The alternative is radiation therapy, which is usually given in combination with chemotherapy. Future pregnancies are not possible after radical hysterectomy or radiation therapy. (See "Patient information: Treatment of abnormal Pap smears" for information about conization and see "Patient information: Vaginal hysterectomy" for information about simple hysterectomy and see "Patient information: Treatment of early stage cervical cancer" for information about radiation therapy and chemotherapy).

Fertility-preserving therapy — Some women who wish to preserve the ability to carry a pregnancy after treatment may be eligible for less aggressive forms of treatment. Treatments that allow a woman to preserve her ability to carry a pregnancy include the following: Conization (currently recommended only for the earliest microscopic cervical cancers that do not invade very deeply into the cervix [stage IA1] cancers) Radical trachelectomy (a management option for stage IA tumors that invade the cervix a little more deeply (stage IA2) and small visible tumors that are smaller than 4 cm (2 inches, stage IB1 tumors)

Trials have not been done to directly compare outcomes and risk of cancer recurrence of fertility preserving surgery versus radical hysterectomy or radiation therapy. However, available studies suggest that, for appropriately selected young women with early stage IA and IB cervical cancers, fertility-preserving surgery is an acceptable option.

Cervical conization — Cervical conization is the surgical removal of a cone-shaped portion of cervix, including the cancerous area (show figure 2). Conization is performed through the vagina. In order for conization to be considered a reasonable treatment for early superficial cervical cancer, the following criteria must be met on the cervical biopsy: Invasion of cancer cells is no deeper than 3 mm into the cervix. There is no evidence of cancer in the lymphatic or blood vessels The margins (edges) of the cone biopsy and samples of the endocervical cells (biopsy or scraping of cells from the lining of the endocervical canal) must have no evidence of abnormal cells.

Conization is usually performed in the operating room after the woman receives either general or regional anesthesia. General anesthesia induces sleep and prevents pain while regional anesthesia (eg, spinal or epidural) delivers medication to the space around the spinal cord to prevent pain while the patient remains awake during the procedure. Most women can go home the same day or the morning after the procedure.

Alternately, a loop electrosurgical excision procedure (LEEP) may be performed using local anesthesia in the physician's office (show figure 3). (See "Patient information: Treatment of abnormal Pap smears" for more information about LEEP).

Following conization, most gynecologic oncologists recommend that the woman avoid sexual intercourse, not place anything in the vagina, and not take a bath or swim for a few weeks (showers are fine); these activities could potentially interfere with healing. Some bleeding is expected, although it should not be heavy. If bleeding becomes heavy (eg, soaks a pad in less than an hour) or continues for more than one week, the woman should contact her healthcare provider.

After conization, follow up examinations are recommended to ensure that there is no evidence of cervical cancer (see "Follow up" below).

Radical trachelectomy — Conization is not an acceptable treatment for women with early stage IA or IB cervical cancer who do not meet the above criteria. Women who have more deeply invading microscopic stage IA tumors (stage IA2 disease) or a visible tumor that is smaller than 4 cm in size (stage IB1 disease) who wish to preserve future fertility may be appropriate candidates for a procedure called radical trachelectomy.

Clinical studies show that the rate of cancer recurrence after radical trachelectomy is similar to the rate of recurrence after radical hysterectomy. However, longer follow up and more clinical studies are needed to confirm this. Trachelectomy is still considered by many experts to be a relatively new, non-standard form of treatment for stage IA2 and IB1 disease.

Radical trachelectomy is defined as partial or complete surgical removal of the cervix and parametria (connective tissues next to the uterus and cervix). Radical trachelectomy removes much more of the cervix compared to cervical conization (show figure 4). The procedure is performed in the operating room after the woman receives either general or regional anesthesia. General anesthesia induces sleep and prevents pain while regional anesthesia (eg, spinal or epidural) delivers medication to the space around the spinal cord to prevent pain in a patient who remains awake during the procedure.

Trachelectomy may be done through an incision in the vagina or abdomen, depending upon the surgeon's preference. The cervix and upper portion of the vagina may be completely or partially removed, depending upon the size and depth of the cancer. A permanent purse-string stitch (cerclage) is placed at the lower end of the uterus or remaining cervix (show figure 4).

Before trachelectomy begins, most women undergo surgical removal of lymph nodes within the pelvis to be sure that the cancer has not spread; this is called lymphadenectomy (show figure 5). The nodes may be removed through an incision in the abdomen (if an abdominal incision made for the trachelectomy), which allows the physician to see the nodes directly.

Alternately, the nodes are removed with the assistance of a laparoscope. When the laparoscope is used to perform the procedure, smaller incisions are made in the abdomen to insert instruments, including a laparoscope and camera, which are used to find and remove selected lymph nodes. If laparoscopic lymphadenectomy is performed, the radical trachelectomy is performed through the vagina.

After removal, the lymph nodes are examined under a microscope to preliminarily confirm that cancer cells are absent. If any nodes are found to contain cancer cells, trachelectomy is not performed, and more aggressive therapy (radical hysterectomy or chemoradiotherapy) is usually recommended. (See "Patient information: Treatment of early stage cervical cancer").

Following trachelectomy, most gynecologic oncologists recommend that the woman avoid sexual intercourse, not place anything in the vagina, or take a bath or swim for four to six weeks (showers are fine); these activities could potentially interfere with healing. Some bleeding is expected for approximately one week, although it should not be heavy. If bleeding becomes heavy (eg, soaks a pad in less than an hour) or continues for more than one week, the woman should contact her healthcare provider.

After trachelectomy, follow up examinations and testing are recommended to ensure that there is no evidence of cervical cancer (see "Follow up" below).

Need for further treatment — Further surgery may be required if abnormal or cancerous cells are found at the margins (edges) of the area that is surgically removed during conization or trachelectomy. For a woman who had conization, this could mean a second conization, radical trachelectomy, or hysterectomy. For a woman who had radical trachelectomy, this usually means a radical hysterectomy. (See "Patient information: Treatment of early stage cervical cancer").

PREGNANCY AFTER TREATMENT — Most women are advised to wait six to 12 months after conization or trachelectomy before attempting to become pregnant to allow the tissue to heal fully. Even if a woman waits to attempt pregnancy, there is a risk of pregnancy complications and/or infertility after cervical cancer treatment.

Infertility — There is an increased risk of difficulty in becoming pregnant if the cervix or lower uterus becomes scarred or narrowed as a result of the conization or radical trachelectomy. This could potentially prevent sperm from entering the uterus. This can usually be overcome with an infertility treatment, such as intrauterine insemination (IUI). With IUI, a small catheter is used to deliver sperm directly into the uterus.

Cervical insufficiency and preterm delivery — Cervical insufficiency occurs when the cervix opens or thins earlier than normal during pregnancy. This can lead to preterm (premature) labor or preterm delivery (when delivery occurs before 37 weeks of pregnancy). Studies show that women who undergo trachelectomy or conization as a treatment for early cervical cancer have an increased risk of preterm delivery.

For these reasons, women who undergo treatment for cervical cancer are followed closely during pregnancy. This generally involves regular monitoring of the length and opening (dilation) of the cervix. (See "Patient information: Preterm labor", section on cervical length).

After cervical conization — For women who undergo cervical conization, studies have found an increased risk of preterm delivery. Following cervical conization, the risk of preterm delivery is almost tripled compared to women who have not undergone conization (14 percent vs. 5 percent). After a LEEP conization, the risk is also increased (11 percent vs. 7 percent). There is less data about the risk of infertility following conization (LEEP or cervical conization), although most experts believe there is a low risk of difficulty in becoming pregnant because of the conization.

For women who develop cervical insufficiency following conization, a cerclage (stitch) can be placed if the cervix opens prematurely during pregnancy (show figure 6). This temporarily helps to keep the cervix closed; it is usually removed near a woman's delivery date or if she develops preterm labor.

After radical trachelectomy — In one review of 355 women who had a radical trachelectomy, approximately 70 percent of women who tried to become pregnant were able to do so. Approximately 20 percent of these women had a first trimester pregnancy loss, and 8 percent of women had a second trimester loss. Preterm deliveries occurred in 20 percent of pregnancies [2]. The risk of first trimester pregnancy loss after radical trachelectomy is about the same as that of women who have not had any cervical surgery, but the risk of second trimester loss and preterm delivery appear to be a higher. (See "Patient information: Miscarriage").

A cerclage is not placed during pregnancy in women who had trachelectomy because a permanent cerclage is placed at the time of trachelectomy (show figure 4). Because of this, most women who become pregnant after trachelectomy require a Cesarean section for delivery.

Pregnancy options after radical hysterectomy or radiation — It is not usually possible to become pregnant or carry a pregnancy after treatment with radical hysterectomy and/or chemoradiotherapy. However, advances in assisted reproductive technology may offer a way for women to have a biologically-related child after this type of treatment.

Embryo cryopreservation is a technique that has been available for many years for fertility preservation. To use embryo cryopreservation, a woman must use fertility medications and undergo a surgical procedure to harvest her oocytes (eggs). The oocyte is then combined with a partner's or donor's sperm to create an embryo. The embryo is then frozen for use at a later time. Embryo cryopreservation requires that radical surgery, chemotherapy, or radiotherapy are delayed for several weeks, and that a partner's or donor's sperm is available. Thus, it may not be an option for all women.

Reproductive techniques that are currently in the experimental phase include oocyte cryopreservation (freezing the egg before it is fertilized with sperm) and ovarian cryopreservation (freezing the ovary); further study is needed before these techniques are available to the general public. All of these techniques, including embryo cryopreservation, would require a gestational (surrogate) carrier to carry the pregnancy. (See "Gestational carrier pregnancy").

A young woman who wishes to preserve her fertility may feel that she has to choose between doing what seems best for her own life and what might be best for preserving fertility. Every woman's situation is different, and every decision must be individualized based upon the woman's situation. Advice regarding options for fertility preservation is available from physicians who are experts in reproductive endocrinology and infertility, in conjunction with a gynecologic oncologist.

FERTILITY PRESERVING TREATMENT VERSUS STANDARD TREATMENT — The most common treatment for early stage cervical cancer is radical hysterectomy (surgical removal of the cervix and uterus). The alternative is radiation therapy, which is usually given in combination with chemotherapy. These are the best-studied treatments with the lowest risk of recurrence in clinical trials. Radical hysterectomy, radiation, and chemotherapy are discussed in detail in a separate topic review. (See "Patient information: Treatment of early stage cervical cancer").

FOLLOW UP — After cervical cancer treatment, including fertility-sparing treatments, periodic follow up testing and examination is recommended. Guidelines from the National Comprehensive Cancer Network (NCCN) suggest the following [3]: 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 only if there is a concern about cancer recurrence.

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, and to 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 should expect in the future. The chances that early stage cervical cancer can be cured are good in most cases. 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 have the standard treatment of 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, althought the cause of death was not necessarily related to the cancer.

For women with stage IA2 cervical cancer, more than 95 percent of women who undergo standard treatment are alive at five years after diagnosis. For stage IB1, 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: The official patient information website of the Society for Gynecologic Oncology

(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)


[1-11]


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. Plante M, Renaud MC, Roy M. Vaginal radical trachelectomy: A valuable fertility-preseving option in the management of early-stage cervical cancer. A series of 50 pregnancies and review of the literature. Gynecol Oncol 2005; 98:3.
3. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology available at www.nccn.org/professionals/physician_gls/default.asp (Accessed February 5, 2007).
4. 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.
5. 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.
6. Dargent, D, Martin, X, Sacchetoni, A, Mathevet, P. Laparoscopic vaginal radical trachelectomy: a treatment to preserve the fertility of cervical carcinoma patients. Cancer 2000; 88:1877.
7. Burnett, AF, Roman, LD, O'Meara, AT, Morrow, CP. Radical vaginal trachelectomy and pelvic lymphadenectomy for preservation of fertility in early cervical carcinoma. Gynecol Oncol 2003; 88:419.
8. Abu-Rustum, NR, Sonoda, Y, Black, D, et al. Fertility-sparing radical abdominal trachelectomy for cervical carcinoma: Technique and review of the literature. Gynecol Oncol 2006; 103:807.
9. Roman, LD. Pregnancy after radical vaginal trachelectomy: Maybe not such a risky undertaking after all. Gynecol Oncol 2005; 98:1.
10. Hertel, H, Kohler, C, Grund, D, et al. Radical vaginal trachelectomy (RVT) combined with laparoscopic pelvic lymphadenectomy: Prospective multicenter study of 100 patients with early cervical cancer. Gynecol Oncol 2006; 103:506.
11. Boss, EA, van Golde, RJ, Beerendonk, CC, Massuger, LF. Pregnancy after radical trachelectomy: a real option?. Gynecol Oncol 2005; 99:S152.

Treatment of early stage cervical cancer for women who desire future pregnancy

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 the earliest stages of localized cervical cancer who wish to preserve their ability to become pregnant in the future. A separate topic review discusses the standard treatment of all early stage cervical cancers (which usually includes hysterectomy). (See "Patient information: Treatment of early stage cervical cancer").

THE CERVIX — The uterus (womb) opens into the vagina through the cervix (show figure 1). Squamous cells make up the outer layer of the cervix. Squamous cell carcinoma of the cervix is the name for cancer that affects these cells.

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 a cancer. Therefore, all women who have a cervix should have regular screening with Pap tests. (See "Patient information: Screening for cervical cancer").

If a cervical cancer does develop, it may initially cause no 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 vaginal 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 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 infection can also cause a noncancerous condition called condyloma (genital warts). (See "Patient information: Condyloma (genital warts) in women").

Most HPV infections are temporary because the body's immune system effectively clears the infection. When certain types of the HPV virus persist in the body, there is a higher likelihood that the viral infection will cause cervical cell abnormalities such as dysplasia or cancer; persistent infections are believed to occur in 10 to 20 percent of women. Evidence of HPV infection can be detected in almost all cervical cancers (squamous cell carcinomas as well as adenocarcinomas). For more information about HPV testing, 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, or 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. If a biopsy shows the presence of a cervical cancer, the woman should consult with a doctor who specializes in cancers of the female reproductive system (called a gynecologic oncologist). 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 (metastasis).

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 an 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 — Early stage cervical cancer refers to stage IA, IB, and some small IIA tumors (show table 1). There are several options for treatment of these women. The optimal choice depends upon the stage, the estimated risk of a cancer recurrence following treatment, the woman's age and plans for future pregnancy, whether underlying medical conditions are present, and the preferences of the patient and her physician.

Radical hysterectomy — For women with early stage cervical cancer who do not plan pregnancy in the future, a radical hysterectomy (surgical removal of the uterus, cervix and upper part of the vagina) is the standard treatment. The alternative is radiation therapy, which is usually given in combination with chemotherapy. Future pregnancies are not possible after radical hysterectomy or radiation therapy. (See "Patient information: Treatment of abnormal Pap smears" for information about conization and see "Patient information: Vaginal hysterectomy" for information about simple hysterectomy and see "Patient information: Treatment of early stage cervical cancer" for information about radiation therapy and chemotherapy).

Fertility-preserving therapy — Some women who wish to preserve the ability to carry a pregnancy after treatment may be eligible for less aggressive forms of treatment. Treatments that allow a woman to preserve her ability to carry a pregnancy include the following: Conization (currently recommended only for the earliest microscopic cervical cancers that do not invade very deeply into the cervix [stage IA1] cancers) Radical trachelectomy (a management option for stage IA tumors that invade the cervix a little more deeply (stage IA2) and small visible tumors that are smaller than 4 cm (2 inches, stage IB1 tumors)

Trials have not been done to directly compare outcomes and risk of cancer recurrence of fertility preserving surgery versus radical hysterectomy or radiation therapy. However, available studies suggest that, for appropriately selected young women with early stage IA and IB cervical cancers, fertility-preserving surgery is an acceptable option.

Cervical conization — Cervical conization is the surgical removal of a cone-shaped portion of cervix, including the cancerous area (show figure 2). Conization is performed through the vagina. In order for conization to be considered a reasonable treatment for early superficial cervical cancer, the following criteria must be met on the cervical biopsy: Invasion of cancer cells is no deeper than 3 mm into the cervix. There is no evidence of cancer in the lymphatic or blood vessels The margins (edges) of the cone biopsy and samples of the endocervical cells (biopsy or scraping of cells from the lining of the endocervical canal) must have no evidence of abnormal cells.

Conization is usually performed in the operating room after the woman receives either general or regional anesthesia. General anesthesia induces sleep and prevents pain while regional anesthesia (eg, spinal or epidural) delivers medication to the space around the spinal cord to prevent pain while the patient remains awake during the procedure. Most women can go home the same day or the morning after the procedure.

Alternately, a loop electrosurgical excision procedure (LEEP) may be performed using local anesthesia in the physician's office (show figure 3). (See "Patient information: Treatment of abnormal Pap smears" for more information about LEEP).

Following conization, most gynecologic oncologists recommend that the woman avoid sexual intercourse, not place anything in the vagina, and not take a bath or swim for a few weeks (showers are fine); these activities could potentially interfere with healing. Some bleeding is expected, although it should not be heavy. If bleeding becomes heavy (eg, soaks a pad in less than an hour) or continues for more than one week, the woman should contact her healthcare provider.

After conization, follow up examinations are recommended to ensure that there is no evidence of cervical cancer (see "Follow up" below).

Radical trachelectomy — Conization is not an acceptable treatment for women with early stage IA or IB cervical cancer who do not meet the above criteria. Women who have more deeply invading microscopic stage IA tumors (stage IA2 disease) or a visible tumor that is smaller than 4 cm in size (stage IB1 disease) who wish to preserve future fertility may be appropriate candidates for a procedure called radical trachelectomy.

Clinical studies show that the rate of cancer recurrence after radical trachelectomy is similar to the rate of recurrence after radical hysterectomy. However, longer follow up and more clinical studies are needed to confirm this. Trachelectomy is still considered by many experts to be a relatively new, non-standard form of treatment for stage IA2 and IB1 disease.

Radical trachelectomy is defined as partial or complete surgical removal of the cervix and parametria (connective tissues next to the uterus and cervix). Radical trachelectomy removes much more of the cervix compared to cervical conization (show figure 4). The procedure is performed in the operating room after the woman receives either general or regional anesthesia. General anesthesia induces sleep and prevents pain while regional anesthesia (eg, spinal or epidural) delivers medication to the space around the spinal cord to prevent pain in a patient who remains awake during the procedure.

Trachelectomy may be done through an incision in the vagina or abdomen, depending upon the surgeon's preference. The cervix and upper portion of the vagina may be completely or partially removed, depending upon the size and depth of the cancer. A permanent purse-string stitch (cerclage) is placed at the lower end of the uterus or remaining cervix (show figure 4).

Before trachelectomy begins, most women undergo surgical removal of lymph nodes within the pelvis to be sure that the cancer has not spread; this is called lymphadenectomy (show figure 5). The nodes may be removed through an incision in the abdomen (if an abdominal incision made for the trachelectomy), which allows the physician to see the nodes directly.

Alternately, the nodes are removed with the assistance of a laparoscope. When the laparoscope is used to perform the procedure, smaller incisions are made in the abdomen to insert instruments, including a laparoscope and camera, which are used to find and remove selected lymph nodes. If laparoscopic lymphadenectomy is performed, the radical trachelectomy is performed through the vagina.

After removal, the lymph nodes are examined under a microscope to preliminarily confirm that cancer cells are absent. If any nodes are found to contain cancer cells, trachelectomy is not performed, and more aggressive therapy (radical hysterectomy or chemoradiotherapy) is usually recommended. (See "Patient information: Treatment of early stage cervical cancer").

Following trachelectomy, most gynecologic oncologists recommend that the woman avoid sexual intercourse, not place anything in the vagina, or take a bath or swim for four to six weeks (showers are fine); these activities could potentially interfere with healing. Some bleeding is expected for approximately one week, although it should not be heavy. If bleeding becomes heavy (eg, soaks a pad in less than an hour) or continues for more than one week, the woman should contact her healthcare provider.

After trachelectomy, follow up examinations and testing are recommended to ensure that there is no evidence of cervical cancer (see "Follow up" below).

Need for further treatment — Further surgery may be required if abnormal or cancerous cells are found at the margins (edges) of the area that is surgically removed during conization or trachelectomy. For a woman who had conization, this could mean a second conization, radical trachelectomy, or hysterectomy. For a woman who had radical trachelectomy, this usually means a radical hysterectomy. (See "Patient information: Treatment of early stage cervical cancer").

PREGNANCY AFTER TREATMENT — Most women are advised to wait six to 12 months after conization or trachelectomy before attempting to become pregnant to allow the tissue to heal fully. Even if a woman waits to attempt pregnancy, there is a risk of pregnancy complications and/or infertility after cervical cancer treatment.

Infertility — There is an increased risk of difficulty in becoming pregnant if the cervix or lower uterus becomes scarred or narrowed as a result of the conization or radical trachelectomy. This could potentially prevent sperm from entering the uterus. This can usually be overcome with an infertility treatment, such as intrauterine insemination (IUI). With IUI, a small catheter is used to deliver sperm directly into the uterus.

Cervical insufficiency and preterm delivery — Cervical insufficiency occurs when the cervix opens or thins earlier than normal during pregnancy. This can lead to preterm (premature) labor or preterm delivery (when delivery occurs before 37 weeks of pregnancy). Studies show that women who undergo trachelectomy or conization as a treatment for early cervical cancer have an increased risk of preterm delivery.

For these reasons, women who undergo treatment for cervical cancer are followed closely during pregnancy. This generally involves regular monitoring of the length and opening (dilation) of the cervix. (See "Patient information: Preterm labor", section on cervical length).

After cervical conization — For women who undergo cervical conization, studies have found an increased risk of preterm delivery. Following cervical conization, the risk of preterm delivery is almost tripled compared to women who have not undergone conization (14 percent vs. 5 percent). After a LEEP conization, the risk is also increased (11 percent vs. 7 percent). There is less data about the risk of infertility following conization (LEEP or cervical conization), although most experts believe there is a low risk of difficulty in becoming pregnant because of the conization.

For women who develop cervical insufficiency following conization, a cerclage (stitch) can be placed if the cervix opens prematurely during pregnancy (show figure 6). This temporarily helps to keep the cervix closed; it is usually removed near a woman's delivery date or if she develops preterm labor.

After radical trachelectomy — In one review of 355 women who had a radical trachelectomy, approximately 70 percent of women who tried to become pregnant were able to do so. Approximately 20 percent of these women had a first trimester pregnancy loss, and 8 percent of women had a second trimester loss. Preterm deliveries occurred in 20 percent of pregnancies [2]. The risk of first trimester pregnancy loss after radical trachelectomy is about the same as that of women who have not had any cervical surgery, but the risk of second trimester loss and preterm delivery appear to be a higher. (See "Patient information: Miscarriage").

A cerclage is not placed during pregnancy in women who had trachelectomy because a permanent cerclage is placed at the time of trachelectomy (show figure 4). Because of this, most women who become pregnant after trachelectomy require a Cesarean section for delivery.

Pregnancy options after radical hysterectomy or radiation — It is not usually possible to become pregnant or carry a pregnancy after treatment with radical hysterectomy and/or chemoradiotherapy. However, advances in assisted reproductive technology may offer a way for women to have a biologically-related child after this type of treatment.

Embryo cryopreservation is a technique that has been available for many years for fertility preservation. To use embryo cryopreservation, a woman must use fertility medications and undergo a surgical procedure to harvest her oocytes (eggs). The oocyte is then combined with a partner's or donor's sperm to create an embryo. The embryo is then frozen for use at a later time. Embryo cryopreservation requires that radical surgery, chemotherapy, or radiotherapy are delayed for several weeks, and that a partner's or donor's sperm is available. Thus, it may not be an option for all women.

Reproductive techniques that are currently in the experimental phase include oocyte cryopreservation (freezing the egg before it is fertilized with sperm) and ovarian cryopreservation (freezing the ovary); further study is needed before these techniques are available to the general public. All of these techniques, including embryo cryopreservation, would require a gestational (surrogate) carrier to carry the pregnancy. (See "Gestational carrier pregnancy").

A young woman who wishes to preserve her fertility may feel that she has to choose between doing what seems best for her own life and what might be best for preserving fertility. Every woman's situation is different, and every decision must be individualized based upon the woman's situation. Advice regarding options for fertility preservation is available from physicians who are experts in reproductive endocrinology and infertility, in conjunction with a gynecologic oncologist.

FERTILITY PRESERVING TREATMENT VERSUS STANDARD TREATMENT — The most common treatment for early stage cervical cancer is radical hysterectomy (surgical removal of the cervix and uterus). The alternative is radiation therapy, which is usually given in combination with chemotherapy. These are the best-studied treatments with the lowest risk of recurrence in clinical trials. Radical hysterectomy, radiation, and chemotherapy are discussed in detail in a separate topic review. (See "Patient information: Treatment of early stage cervical cancer").

FOLLOW UP — After cervical cancer treatment, including fertility-sparing treatments, periodic follow up testing and examination is recommended. Guidelines from the National Comprehensive Cancer Network (NCCN) suggest the following [3]: 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 only if there is a concern about cancer recurrence.

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, and to 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 should expect in the future. The chances that early stage cervical cancer can be cured are good in most cases. 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 have the standard treatment of 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, althought the cause of death was not necessarily related to the cancer.

For women with stage IA2 cervical cancer, more than 95 percent of women who undergo standard treatment are alive at five years after diagnosis. For stage IB1, 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: The official patient information website of the Society for Gynecologic Oncology

(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)


[1-11]


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. Plante M, Renaud MC, Roy M. Vaginal radical trachelectomy: A valuable fertility-preseving option in the management of early-stage cervical cancer. A series of 50 pregnancies and review of the literature. Gynecol Oncol 2005; 98:3.
3. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology available at www.nccn.org/professionals/physician_gls/default.asp (Accessed February 5, 2007).
4. 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.
5. 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.
6. Dargent, D, Martin, X, Sacchetoni, A, Mathevet, P. Laparoscopic vaginal radical trachelectomy: a treatment to preserve the fertility of cervical carcinoma patients. Cancer 2000; 88:1877.
7. Burnett, AF, Roman, LD, O'Meara, AT, Morrow, CP. Radical vaginal trachelectomy and pelvic lymphadenectomy for preservation of fertility in early cervical carcinoma. Gynecol Oncol 2003; 88:419.
8. Abu-Rustum, NR, Sonoda, Y, Black, D, et al. Fertility-sparing radical abdominal trachelectomy for cervical carcinoma: Technique and review of the literature. Gynecol Oncol 2006; 103:807.
9. Roman, LD. Pregnancy after radical vaginal trachelectomy: Maybe not such a risky undertaking after all. Gynecol Oncol 2005; 98:1.
10. Hertel, H, Kohler, C, Grund, D, et al. Radical vaginal trachelectomy (RVT) combined with laparoscopic pelvic lymphadenectomy: Prospective multicenter study of 100 patients with early cervical cancer. Gynecol Oncol 2006; 103:506.
11. Boss, EA, van Golde, RJ, Beerendonk, CC, Massuger, LF. Pregnancy after radical trachelectomy: a real option?. Gynecol Oncol 2005; 99:S152.

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.