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cervical cancer |
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Cervical Cancer DefinitionCervical cancer is a disease in which the cells of the cervix become abnormal and start to grow uncontrollably, forming tumors. DescriptionIn the United States, cervical cancer is the fifth most common cancer among women aged 35-54, and the third most common cancer of the female reproductive tract. In some developing countries, it is the most common type of cancer. It generally begins as an abnormality in the cells on the outside of the cervix. The cervix is the lower part or neck of the uterus (womb). It connects the body of the uterus to the vagina (birth canal). Approximately 90% of cervical cancers are squamous cell carcinomas. This type of cancer originates in the thin, flat, squamous cells on the surface of the ectocervix, the part of the cervix that is next to the vagina. (Squamous cells are the thin, flat cells of the surfaces of the skin and cervix and linings of various organs.) Another 10% of cervical cancers are of the adenocarcinoma type. This cancer originates in the mucus-producing cells of the inner or endocervix, near the body of the uterus. Occasionally, the cancer may have characteristics of both types and is called adenosquamous carcinoma or mixed carcinoma. The initial changes that may occur in some cervical cells are not cancerous. However, these precancerous cells form a lesion called dysplasia or a squamous intraepithelial lesion (SIL), since it occurs within the epithelial or outer layer of cells. These abnormal cells can also be described as cervical intraepithelial neoplasia (CIN). Moderate to severe dysplasia may be called carcinoma in situ or non-invasive cervical cancer. Dysplasia is a common condition and the abnormal cells often disappear without treatment. However, these precancerous cells can become cancerous. This may take years, although it can happen in less than a year. Eventually, the abnormal cells start to grow uncontrollably into the deeper layers of the cervix, becoming an invasive cervical cancer. Although cervical cancer used to be one of the most common causes of cancer death among American women, in the past 40 years there has been a 75% decrease in mortality. This is primarily due to routine screening with Pap tests (Pap smear), to identify precancerous and early-invasive stages of cervical cancer. With treatment, these conditions have a cure rate of nearly 100%. Worldwide, there are more than 400,000 new cases of cervical cancer diagnosed each year. The American Cancer Society (ACS) estimated 13,000 new cases of invasive cervical cancer diagnosed in the United States in 2002. More than one million women were diagnosed with a precancerous lesion or non-invasive cancer of the cervix in 2001. Older women are at the highest risk for cervical cancer. Although girls under the age of 15 rarely develop this cancer, the risk factor begins to increase in the late teens. Rates for carcinoma in situ peak between the ages of 20 and 30. In the United States, the incidence of invasive cervical cancer increases rapidly with age for African-American women over the age of 25. The incidence rises more slowly for Caucasian women. However, women over age 65 account for more than 25% of all cases of invasive cervical cancer. The incidence of cervical cancer is highest among poor women and among women in developing countries. In the United States, the death rates from cervical cancer are higher among Hispanic, Native American, and African-American women than among Caucasian women. These groups of women are much less likely to receive regular Pap tests. Therefore, their cervical cancers usually are diagnosed at a much later stage, after the cancer has spread to other parts of the body. Causes and symptomsHuman papillomavirusInfection with the common human papillomavirus (HPV) is a cause of approximately 90% of all cervical cancers. There are more than 80 types of HPV. About 30 of these types can be transmitted sexually, including those that cause genital warts (papillomas). About half of the sexually transmitted HPVs are associated with cervical cancer. These "high-risk" HPVs produce a protein that can cause cervical epithelial cells to grow uncontrollably. The virus makes a second protein that interferes with tumor suppressors that are produced by the human immune system. The HPV-16 strain is thought to be a cause of about 50% of cervical cancers. More than six million women in the United States have persistent HPV infections, for which there are no cure. Nevertheless, most women with HPV do not develop cervical cancer. Symptoms of invasive cervical cancerMost women do not have symptoms of cervical cancer until it has become invasive. At that point, the symptoms may include:
Once the cancer has invaded the tissue surrounding the cervix, a woman may experience pain in the pelvic region and heavy bleeding from the vagina. DiagnosisThe pap testMost often, cervical cancer is first detected with a Pap test that is performed as part of a regular pelvic examination. The vagina is spread with a metal or plastic instrument called a speculum. A swab is used to remove mucus and cells from the cervix. This sample is sent to a laboratory for microscopic examination. The Pap test is a screening tool rather than a diagnostic tool. It is very efficient at detecting cervical abnormalities. The Bethesda System commonly is used to report Pap test results. A negative test means that no abnormalities are present in the cervical tissue. A positive Pap test describes abnormal cervical cells as low-grade or high-grade SIL, depending on the extent of dysplasia. About 5-10% of Pap tests show at least mild abnormalities. However, a number of factors other than cervical cancer can cause abnormalities, including inflammation from bacteria or yeast infections. A few months after the infection is treated, the Pap test is repeated. BiopsyFollowing an abnormal Pap test, a colposcopy is usually performed. The physician uses a magnifying scope to view the surface of the cervix. The cervix may be coated with an iodine solution that causes normal cells to turn brown and abnormal cells to turn white or yellow. This is called a Schiller test. If any abnormal areas are observed, a colposcopic biopsy may be performed. A biopsy is the removal of a small piece of tissue for microscopic examination by a pathologist. Other types of cervical biopsies may be performed. An endocervical curettage is a biopsy in which a narrow instrument called a curette is used to scrape tissue from inside the opening of the cervix. A cone biopsy, or conization, is used to remove a cone-shaped piece of tissue from the cervix. In a cold knife cone biopsy, a surgical scalpel or laser is used to remove the tissue. A loop electrosurgical excision procedure (LEEP) is a cone biopsy using a wire that is heated by an electrical current. Cone biopsies can be used to determine whether abnormal cells have invaded below the surface of the cervix. They also can be used to treat many precancers and very early cancers. Biopsies may be performed with a local or general anesthetic. They may cause cramping and bleeding. Diagnosing the stageFollowing a diagnosis of cervical cancer, various procedures may be used to stage the disease (determine how far the cancer has spread). For example, additional pelvic exams may be performed under anesthesia. There are several procedures for determining if cervical cancer has invaded the urinary tract. With cystoscopy, a lighted tube with a lens is inserted through the urethra (the urine tube from the bladder to the exterior) and into the bladder to examine these organs for cancerous cells. Tissue samples may be removed for microscopic examination by a pathologist. Intravenous urography (intravenous pyelogram or IVP) is an x ray of the urinary system, following the injection of special dye. The kidneys remove the dye from the bloodstream and the dye passes into the ureters (the tubes from the kidneys to the bladder) and bladder. IVP can detect a blocked ureter, caused by the spread of cancer to the pelvic lymph nodes (small glands that are part of the immune system). A procedure called proctoscopy or sigmoidoscopy is similar to cystoscopy. It is used to determine whether the cancer has spread to the rectum or lower large intestine. Computed tomography (CT) scans, ultrasound, or other imaging techniques may be used to determine the spread of cancer to various parts of the body. With a CT scan, an x-ray beam rotates around the body, taking images from various angles. It is used to determine if the cancer has spread to the lymph nodes. Magnetic resonance imaging (MRI), which uses a magnetic field to image the body, sometimes is used for evaluating the spread of cervical cancer. Chest x rays may be used to detect cervical cancer that has spread to the lungs. TreatmentFollowing a diagnosis of cervical cancer, the physician takes a medical history and performs a complete physical examination. This includes an evaluation of symptoms and risk factors for cervical cancer. The lymph nodes are examined for evidence that the cancer has spread from the cervix. The choice of treatment depends on the clinical stage of the disease. The figo system of stagingThe International Federation of Gynecologists and Obstetricians (FIGO) system usually is used to stage cervical cancer:
In addition to the stage of the cancer, factors such as a woman's age, general health, and preferences may influence the choice of treatment. The exact location of the cancer within the cervix and the type of cervical cancer also are important considerations. Treatment of precancer and carcinoma in situMost low-grade SILs that are detected with Pap tests revert to normal without treatment. Most high-grade SILs require treatment. Treatments to remove precancerous cells include:
These methods also may be used to treat cancer that is confined to the surface of the cervix (stage 0) and other early-stage cervical cancers in women who may want to become pregnant. They may be used in conjunction with other treatments. These procedures may cause bleeding or cramping. All of these treatments require close follow-up to detect any recurrence of the cancer. SurgeryA simple hysterectomy is used to treat some stages 0 and IA cervical cancers. Usually only the uterus is removed, although occasionally the fallopian tubes and ovaries are removed as well. The tissues adjoining the uterus, including the vagina, remain intact. The uterus may be removed either through the abdomen or the vagina. In a radical hysterectomy, the uterus and adjoining tissues, including the ovaries, the upper region (1 in) of the vagina near the cervix, and the pelvic lymph nodes, are all removed. A radical hysterectomy usually involves abdominal surgery. However, it can be performed vaginally, in combination with a laparoscopic pelvic lymph node dissection. With laparoscopy, a tube is inserted through a very small surgical incision for the removal of the lymph nodes. These operations are used to treat stages IA2, IB, and IIA cervical cancers, particularly in young women. Following a hysterectomy, the tissue is examined to see if the cancer has spread and requires additional radiation treatment. Women who have had hysterectomies cannot become pregnant, but complications from a hysterectomy are rare. If cervical cancer recurs following treatment, a pelvic exenteration (extensive surgery) may be performed. This includes a radical hysterectomy, with the additional removal of the bladder, rectum, part of the colon, and/or all of the vagina. Such operations require the creation of new openings for the urine and feces. A new vagina may be created surgically. Often the clitoris and other outer genitals are left intact. Recovery from a pelvic exenteration may take six months to two years. This treatment is successful with 40-50% of recurrent cervical cancers that are confined to the pelvis. If the recurrent cancer has spread to other organs, radiation or chemotherapy may be used to alleviate some of the symptoms. RadiationRadiation therapy, which involves the use of high-dosage x rays or other high-energy waves to kill cancer cells, often is used for treating stages IB, IIA, and IIB cervical cancers, or in combination with surgery. With external-beam radiation therapy, the rays are focused on the pelvic area from a source outside the body. With implant or internal radiation therapy, a pellet of radioactive material is placed internally, near the tumor. Alternatively, thin needles may be used to insert the radioactive material directly into the tumor. Radiation therapy to the pelvic region can have many side effects:
ChemotherapyChemotherapy, the use of one or more drugs to kill cancer cells, is used to treat disease that has spread beyond the cervix. Most often it is used following surgery or radiation treatment. Stages IIB, III, IV, and recurrent cervical cancers usually are treated with a combination of external and internal radiation and chemotherapy. The common drugs used for cervical cancer are cisplatin, ifosfamide, and fluorouracil. These may be injected or taken by mouth. The National Cancer Institute recommends that chemotherapy with cisplatin be considered for all women receiving radiation therapy for cervical cancer. The side effects of chemotherapy depend on a number of factors, including the type of drug, the dosage, and the length of the treatment. Side effects may include:
With the exception of menopause and infertility, most of the side effects are temporary. Alternative treatmentBiological therapy sometimes is used to treat cervical cancer, either alone or in combination with chemotherapy. Treatment with the immune-system protein interferon is used to boost the immune response. Biological therapy can cause temporary flu-like symptoms and other side effects. Some research suggests that vitamin A (carotene) may help to prevent or stop cancerous changes in cells such as those on the surface of the cervix. Other studies suggest that vitamins C and E may reduce the risk of cervical cancer. PrognosisFor cervical cancers that are diagnosed in the preinvasive stage, the five-year-survival rate is almost 100%. When cervical cancer is detected in the early invasive stages, approximately 91% of women survive five years or more. Stage IVB cervical cancer is not considered to be curable. The five-year-survival rate for all cervical cancers combined is about 70%. The death rate from cervical cancer continues to decline by about 2% each year. Women over age 65 account for 40-50% of all deaths from cervical cancer. About 4,100 women died of the disease in the United States in 2002. PreventionViral infectionsMost cervical cancers are preventable. More than 90% of women with cervical cancer are infected with HPV. HPV infection is the single most important risk factor. This is particularly true for young women because the cells lining the cervix do not fully mature until age 18. These immature cells are more susceptible to cancer-causing agents and viruses. Since HPV is a sexually-transmitted infection, sexual behaviors can put women at risk for HPV infection and cervical cancer. These behaviors include:
HPV infection may not produce any symptoms, so sexual partners may not know that they are infected. In 2003, a new DNA screening test was approved by the FDA to test for HPV at the same time as the Pap test. Condoms do not necessarily prevent HPV infection. However, in 2003, a preliminary study demonstrated that a vaccine against the type of HPV that causes the most cervical cancers showed promise in preventing HPV infection. Scientists predict having FDA approval of an HPV vaccine by about 2008 or 2010. Infection with the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) is a risk factor for cervical cancer. Women who test positive for HIV may have impaired immune systems that cannot correct precancerous conditions. Furthermore, sexual behavior that puts women at risk for HIV infection, also puts them at risk for HPV infection. There is some evidence suggesting that another sexually transmitted virus, the genital herpes virus, also may be involved in cervical cancer. SmokingSmoking may double the risk of cervical cancer. In fact, studies suggest that nearly 50% of women diagnosed with cervical cancer smoke. Chemicals produced by tobacco smoke can damage the DNA of cervical cells. The risk increases with the number of years a woman smokes and the amount she smokes. A 2003 study also linked smoking to poorer outcomes and survivals in cervical cancer patients. Diet and drugsDiets that are low in fruits and vegetables increase the risk of cervical cancer. A 2003 study also linked obesity to increased risk for cervical adenocarcinoma. Even women who were overweight had a higher incidence of the disease. The link appears to be increase levels of estrogen. Excessive fat tissue influences levels of estrogen and other sex hormones. Women also have an increased risk of cervical cancer if their mothers took the drug diethylstilbestrol (DES) while they were pregnant. This drug was given to women between 1940 and 1971 to prevent miscarriages. Some statistical studies have suggested that the long-term use of oral contraceptives may slightly increase the risk of cervical cancer. Pap testsMost cases of cervical cancers are preventable, since they start with easily detectable precancerous changes. Therefore, the best prevention for cervical cancer is a regular Pap test. The ACS revised its guidelines for regular screening in late 2002. In brief, women should begin having Pap tests about three years after having sexual intercourse, but no later than 21 years of age. Women should continue screening every year with regular Pap tests until age 30. Once a woman has had three normal results in a row, she may get screened every two to three years. A doctor may suggest more frequent screening if a woman has certain risk factors for cervical cancer. Women who have had total hysterectomies including the removal of the cervix and those over age 70 who have had three normal results generally do not need to continue having Pap tests under the new guidelines. The National Breast and Cervical Cancer Early Detection Program provides free or low-cost Pap tests and treatment for women without health insurance, for older women, and for members of racial and ethnic minorities. The program is administered through individual states, under the direction of the Centers for Disease Control and Prevention. Special concernsIf a woman is diagnosed with very early-stage (IA) cervical cancer while pregnant, the physician usually will recommend a hysterectomy after the baby is born. For later-stage cancers, the pregnancy is terminated or the baby is removed by cesarean section as soon as it can survive outside the womb. This is followed by a hysterectomy and/or radiation treatment. For the most advanced stages of cervical cancer, treatment is initiated despite the pregnancy. Many women with cervical cancer have hysterectomies, which are major surgeries. Although normal activities, including sexual intercourse, can be resumed in four to eight weeks, a woman may have emotional problems following a hysterectomy. A strong support system can help with these difficulties. Key termsAdenocarcinoma — Cervical cancer that originates in the mucus-producing cells of the inner or endocervix. Biopsy — Removal of a small sample of tissue for examination under a microscope; used for the diagnosis and treatment of cervical cancer and precancerous conditions. Carcinoma in situ — Cancer that is confined to the cells in which it originated and has not spread to other tissues. Cervical intraepithelial neoplasia (CIN) — Abnormal cell growth on the surface of the cervix. Cervix — Narrow, lower end of the uterus forming the opening to the vagina. Colposcopy — Diagnostic procedure using a hollow, lighted tube (colposcope) to look inside the cervix and uterus. Conization — Cone biopsy; removal of a cone-shaped section of tissue from the cervix for diagnosis or treatment. Dysplasia — Abnormal cellular changes that may become cancerous. Endocervical curettage — Biopsy performed with a curette to scrape the mucous membrane of the cervical canal. Human papillomavirus (HPV) — Virus that causes abnormal cell growth (warts or papillomas); some types can cause cervical cancer. Hysterectomy — Removal of the uterus. Interferon — Potent immune-defense protein produced by viral-infected cells; used as an anti-cancer and anti-viral drug. Laparoscopy — Laparoscopic pelvic lymph node dissection; insertion of a tube through a very small surgical incision to remove lymph nodes. Loop electrosurgical excision procedure (LEEP) — Cone biopsy performed with a wire that is heated by electrical current. Lymph nodes — Small round glands, located throughout the body, that filter the lymphatic fluid; part of the body's immune defense. Pap test — Pap smear; removal of cervical cells to screen for cancer. Pelvic exenteration — Extensive surgery to remove the uterus, ovaries, pelvic lymph nodes, part or all of the vagina, and the bladder, rectum, and/or part of the colon. Squamous cells — Thin, flat cells on the surfaces of the skin and cervix and linings of various organs. Squamous intraepithelial lesion (SIL) — Abnormal growth of squamous cells on the surface of the cervix. Vaginal stenosis — Narrowing of the vagina due to a build-up of scar tissue. ResourcesBooksHolland, Jimmie C., and Sheldon Lewis. The Human Side of Cancer: Living with Hope, Coping with Uncertainty. New York: HarperCollins, 2000. Runowicz, Carolyn D., Jeanne A. Petrek, and Ted S. Gansler. Women and Cancer: A Thorough and Compassionate Resource for Patients and their Families. New York: Villard Books, 1999. Periodicals"American Cancer Society Issues New Early Detection Guidelines." Women's Health Weekly December 19, 2002: 12. "Get Ready to Take Cervical Cancer Screening to the Next Level: Newly Approved Human Papillomavirus Test Offers 2-in-1 Package." Contraceptive Technology Update June 2003: 61-64. "Obesity Linked to Cervical Adenocarcinoma, a Hormone-Dependent Cancer." Cancer Weekly July 29, 2003: 59. "Study: HPV Test Is more Effective than Pap Smear for Cervical Cancer Screening." Biotech Week December 31, 2003: 143. Van Kessel, Katherine, Koutsky, and Laura. "The HPV Vaccine: Will it One Day Wipe Out Cervical Cancer?" Contemporary OB/GYN November 2003: 71-75. Walgate, Robert. "Vaccine Against Cervical Cancer Passes Proof of Principle." Bulletin of the World Health Organization January-February 2003: 73-81. Worcester, Sharon."Smoking Tied to Poorer Outcomes in Cervical Ca: Locally Advanced Disease." Family Practice News May 15, 2003: 29-31. OrganizationsEyes On The Prize. Org. 446 S. Anaheim Hills Road, #108, Anaheim Hills, CA 92807. http://www.eyesontheprize.org. On-line information and emotional support for women with gynecologic cancer. Other"Cancer of the Cervix." CancerNet. 12 Dec. 2000. National Cancer Institute. NIH Publication No. 95-2047. April 3, 2001. http://cancernet.nci.nih.gov/wyntk_pubs/cervix.htm#2. "Cervical Cancer." Cancer Resource Center. American Cancer Society. Mar 16, 2000. [cited April 3, 2001]. 〈http://www3.cancer.org/cancerinfo/load_cont.asp?ct=8&doc=25&Language=English〉. cervical cancer, a neoplasm of the uterine cervix that can be detected in the early, curable stage by the Papanicolaou (Pap) test. The exact cause is unknown, but factors that may be associated with the development of cervical cancer are coitus at an early age, relations with many sexual partners, genital herpesvirus infections (such as cytomegalovirus), human papillomavirus (HPV), multiparity, and poor obstetric and gynecologic care. Early cervical neoplasia is usually asymptomatic, but there may be a watery vaginal discharge or occasional spotting of blood; advanced lesions may cause a dark, foul-smelling vaginal discharge, leakage from bladder or rectal fistulas, anorexia, weight loss, and back and leg pains. Pap smears of cervical cells are highly important in screening, but definitive diagnoses are based on colposcopic examination and cytologic study of specimens obtained by biopsy. Cervical dysplasia may regress, persist, or progress to clinical disease, but carcinoma in situ is considered to be a precursor of invasive carcinoma. About 90% of cervical tumors are squamous cell carcinomas, fewer than 10% are adenocarcinomas, and others are mixtures of these kinds, or, in rare cases, sarcomas. Cervical cancer invades the tissues of adjacent organs and may metastasize through lymphatic channels to distant sites, including the lungs, bone, liver, brain, and paraaortic nodes. Treatment depends on the kind and the extent of the malignancy, the age of the woman, and her general health. Also considered are her wishes in regard to maintaining her reproductive function. Carcinoma in situ may be treated by excisional conization or cryosurgery. Invasive tumors may be treated with radiotherapy or hysterectomy. Chemotherapy has a mainly palliative role. Vaccination against HPV types 16 and 18, which are responsible for most cervical cancer cases, is now recommended for young women as a preventive measure. cervical cancer Oncology Invasive malignancy of the uterine cervix Epidemiology Incidence is 2.5-fold > in black ♀ Prevention Regular pelvic exams, pap smears Clinical Abnormal bleeding Pathology SCC–85%, adenoCA–10%
Management Cryosurgery, cauterization, laser surgery Prognosis Poor if advanced; CC-related deaths are ugly; death is accompanied by uremia, and a typical 'funky' urinary odor. See Conization, LEEP. Cf Cervical intraepithelial neoplasia
Cervical cancer staging
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Women smokers who have high levels of the human papilloma virus (HPV) face a 27-fold increased risk of cervical cancer compared to smokers with no HPV, according to a recent Swedish study. And the way it protects you from cervical cancer is by helping stop the spread of a serious sexually transmitted disease, HPV. Even though the HPV infection rate is high, cervical cancer rates steadily decreased 75 percent from the mid-1950s to 1992, and the rate of death from cervical cancer continues to decline at an annual rate of 4 percent. |
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