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  Cervical cancerHighlightsHuman Papilloma Virus (HPV) Prevalence About 25% of women age 14 - 59 are infected with the human papilloma virus (HPV), indicates a 2007 study in the Journal of the American Medical Association (JAMA). HPV prevalence is highest (45%) among women age 20 - 24. HPV is the main cause of cervical cancer. Immunization Guidelines In 2006, the FDA approved the first vaccine to prevent cervical cancer. Gardasil protects against human papilloma virus (HPV) 16 and 18, the strains most likely to cause cervical cancer, and HPV 6 and 11, the strains most likely to cause genital warts. In 2007, several expert groups released immunization guidelines for the cervical cancer vaccine. Guidelines from the U.S. Centers for Disease Control’s Advisory Committee on Immunization Practices recommend:
Vaccine Effectiveness
HPV and Throat Cancer Human papilloma virus (HPV) 16 increases the risk of oropharyngeal cancers of the throat, tonsils, and back of the tongue, according to several 2007 studies. HPV can be transmitted during oral sex, causing infection in the mouth. (However, not all people who engage in oral sex or who have oral HPV infection will develop throat cancer. The virus usually goes away on its own.) Previously, alcohol and tobacco use were considered the main risk factors for oropharyngeal cancer. IntroductionThe cervix is the lower third portion of the uterus (womb). It serves as a neck to connect the uterus to the vagina. The opening of the cervix, called the os, remains small and narrow, except during childbirth when it widens to allow a baby to pass from the uterus into the vagina.  The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth. Cervical cancer develops in the thin layer of cells called the epithelium, which cover the cervix. Cells found in the this tissue have different shapes:
Cervical cancer usually begins slowly with precancerous abnormalities, and even if cancer develops, it generally progresses very gradually. Cervical cancer is the most preventable type of cancer and is very treatable in its early stages. Regular Pap tests and human papilloma virus (HPV) screening can help detect this disease early. Precancerous Changes in the CervixDysplasia. Dysplasia is a term that refers to a precancerous condition. It may become cancerous, but not always. In the case of cervical cancer, dysplasia indicates that the layer of cells that covers the cervix (squamous epithelial cells) are abnormal in size and shape and are beginning to grow. Cervical Intraepithelial Neoplasia. Dysplastic changes seen on a Pap smear may indicate the presence of cervical intraepithelial neoplasia (CIN). This means precancerous changes are found within the lining of the cervix. The changes are categorized according to severity: CIN I, CIN II, and CIN III.
 Click the icon to see an image of cervical dysplasia. Invasive Cervical CancerThe cells of the epithelium rest on a very thin layer called the basement membrane. Invasive cervical cancer occurs when cancer cells in the epithelium cross this membrane and invade the stroma, the underlying supportive tissue of the cervix. In later stages, the original cancer may spread to areas surrounding the uterus and cervix or near organs such as the bladder or rectum. It may also spread to distant sites in the body through the bloodstream or the lymph nodes. CausesThe human papillomavirus (HPV) has been detected in virtually all invasive cervical cancers and has been confirmed as the major cause of this cancer. How HPV Is Transmitted. HPV is spread primarily by having sex with an infected partner. Most sexually active young women become infected with this virus, but only 10% remain infected for more than 5 years. Only those infected for longer than 5 years have a higher risk (about 50% above normal). Other factors are then needed to trigger the disease. How HPV Contributes to Cervical Cancer. Researchers believe that most cervical cancers develop when various aggressive genetic HPV strains activate certain oncogenes (cancer-causing genes). Oncogenes called E6 and E7 are particularly important because they interfere with certain protective proteins, such as p53 and pRb, respectively. Under normal conditions, these proteins limit cell growth. Once they are blocked, cell growth can run rampant, leading to tumor development and cancer. HPV Genetic Types. More than 30 genetic variants of human papillomaviruses can be passed through sexual contact form one person to another. The severity, however, varies widely according to genetic type. (Women initially infected by one type of HPV are still at risk for infection from other types.) In women with cervical intraepithelial neoplasia I , the HPV viruses that are present are often types 6 and 11, which are low risk. Other low-risk HPV genetic types are 40, 42, 43, 44, 54, 61, 70, 72, and 81. These viral types often produce genital warts (condylomata) that rarely lead to cancer. (These warts usually affect the woman's genitals, the vagina, and vulva, rather than the cervix.) Of the high-risk types, HPV types 16 and 18 have long been known to be particularly dangerous. These two genetic types and six others (31, 33, 35, 45, 52, and 58) account for 95% of HPV-related cervical cancers. Other high-risk types are 39, 51, 56, 59, 68, 73, and 82. All are associated with moderate cervical intraepithelial neoplasia II and cervical intraepithelial neoplasia III. Types 26, 53, and 66 are also considered high-risk. In 2007, several studies indicated that HPV-16 infection in the mouth is associated with increased risk for oropharyngeal cancer. (Oropharyngeal cancer develops in the throat, just behind the mouth. It includes the base of the tongue, soft palate, tonsils, and side and back walls of the throat.) Prior to this research, alcohol and tobacco were thought to be the main risk factors for this type of cancer. According to the studies, oral sex (both fellatio and cunnilingus) significantly increases the risk of HPV-16 transmission and, therefore, the risk of developing oropharyngeal cancer. While the risk of HPV-16 causing oropharyngeal cancer is lower than the risk of it causing cervical cancer, experts think that the HPV vaccine may help reduce the incidence of throat, tonsil, and tongue cancers, as well as cervical cancer. High-risk types of HPV have also been associated with an increased risk for other cancers, including other genital and lung cancers. The high-risk viruses generally produce flat and nearly invisible growths, compared to the usually harmless warts caused by low-risk HPV viruses. Other Sexually Transmitted DiseasesHerpes viruses. Certain herpes viruses, including herpes simplex virus 6, 2, 7, and cytomegalovirus, have been detected in women with cervical cancer. herpes simplex virus 6 is under particular suspicion for playing a role in activating the papilloma virus gene. The presence of these very common viruses, however, may simply be coincidental, and they may serve no purpose other than being bystanders. Chlamydia Trachomatis. Studies are finding an especially strong association between the incidence of Chlamydiatrachomatis, a sexually transmitted infection, and HPV. (Chlamydia trachomatis should not be confused with Chlamydia pneumoniae, a common cause of mild pneumonia in young adults. Chlamydia pneumonia e is not associated with cervical cancer.) Other Sexually Transmitted Diseases. Other sexually transmitted diseases that have been associated with cervical cancer include HIV and gonorrhea. These infections, however, also may only be markers of increased sexual activity and may not themselves cause cancer. Risk FactorsAccording to the American Cancer Society, about 11,150 new cases of invasive cervical cancer will be diagnosed in the U.S. in 2007. However, the number of new cervical cancer cases has been declining steadily over the past decades. Fifty percent of cervical cancer diagnoses occur in women ages 35 - 55, and slightly more than 20% occur in women over 65 years of age. Some women (15%) develop cervical cancer before the age of 30. Although cervical cancer is rare in women under age 20, cancer rates in younger women are on the rise. Many young women are infected with multiple types of human papillomavirus, which can increase their risk of getting cervical cancer. Young women with early abnormal changes who do not have regular examinations are at high risk for localized cancer by the time they are age 40, and for invasive cancer by age 50. Although it is the most preventable type of cancer, cervical cancer is ranked as the second most common cause of female death. Each year it kills an estimated 3,700 women in the U.S. and nearly 300,000 women worldwide. In the United States, cervical cancer mortality rates plunged by 74% from 1955 - 1992 thanks to increased screening and early detection with the Pap test. Socioeconomic and Ethnic FactorsAlthough the rate of cervical cancer has declined in both Caucasian and African-American women over the past decades, it remains much more prevalent in African-Americans -- whose death rates are twice as high as Caucasian women. Hispanic American women have more than twice the risk of invasive cervical cancer as Caucasian women, also due to a lower rate of screening. These differences, however, are almost certainly due to social and economic differences. Numerous studies report that high poverty levels are linked with low screening rates. In addition, lack of health insurance, limited transportation, and language difficulties hinder a poor woman’s access to screening services. Researchers are investigating programs that provide screening and treatment for women with abnormal Pap smears in a single visit. Specific Risk Factors for Human Papilloma virusThe human papilloma virus (HPV) is the primary cause of cervical cancer. According to a 2007 study in the Journal of the American Medical Association, about 1 in 4 U.S. females ages 14 - 59 are infected with HPV. The prevalence of HPV is highest (45%) in women age 20 - 24. The risk for cervical cancer in infected women appears to be highest in those infected with HPV for more than 6 months. In most people, the virus goes away within a year. However, it persists in about 10% of infected women. High Sexual Activity. In adults, the most important risk factor for HPV is sexual activity with an infected person. Women most at risk for cervical cancer are those with a history of multiple sexual partners, sexual intercourse at 17 years or younger, or both. A woman who has never been sexually active has a very low risk for developing cervical cancer. Sexual activity with multiple partners increases the likelihood of many infections in addition to human papilloma virus. Douching. Women who douche on a weekly basis are more likely to contract cervical cancer than those who do not. Douching may destroy the natural antiviral substances normally present in the vagina, making women more susceptible to HPV. Pessaries. Use of a pessary (a ring-shaped plastic device that keeps the vagina and uterus from collapsing) increases the risk of chronic inflammation and viral infection at the insertion site and therefore may increase the risk for cervical cancer. Risk Factors for HPV in Children and Infants. HPV also can occur in children and even newborns. The virus may also be transmitted by an infected mother. In children, HPV is usually the harmless form that cause skin warts. GeneticsIn one analysis, 15 - 20% of women with cervical cancer had at least one close relative with the disease. Two studies have also reported that in families with cervical cancer there have also been higher rates of other human papilloma virus-related and smoking-associated cancers. Inherited factors in such cases most likely cause changes in the immune system that make such people more susceptible to human papilloma virus or other viruses. Use of Oral ContraceptivesSeveral studies, including a major analysis, have reported a strong association between cervical cancer and long-term use of oral contraception (OC). Women who have taken OCs for more than 10 years have a much higher risk of human papilloma virus (HPV) infection (up to four times higher) than those who do not use OCs. (Women taking OCs for fewer than 5 years have no significantly higher risk.) The reasons for this risk from OC use are not entirely clear. Women who use OCs may be less likely to use a diaphragm, condoms, or other methods that offer some protection against sexual transmitted diseases, including HPV. Some researchers also suggest that the hormones in OCs might help the virus enter the genetic material of cervical cells. Having Many ChildrenStudies indicate that having many children increases the risk for developing cervical cancer, particularly in women with human papilloma virus. SmokingSmoking is associated with a higher risk for precancerous changes (dysplasia) in the cervix and for progression to invasive cervical cancer. Smoking may cause human papilloma virus (HPV) to grow faster and increase its likelihood of causing cancer. According to a 2006 study, women smokers who have HPV-16 are 14 times more likely to develop cervical pre-invasive cancer than smokers who do not have the virus. By contrast, non-smokers with HPV-16 were only 6 times more likely to develop cancer than those who were not infected. Secondhand smoke is also linked to increased risk for cervical cancer tumors. It is not clear if this association is due to cigarette smoke’s direct cancer-causing effects or general damage to the immune system. Cigarette smokers are also deficient in folate, a B vitamin. Folate deficiency may play a role in the development of dysplasia. Exposure to ChemicalsDiethylstilbestrol. From 1938 - 1971, diethylstilbestrol, an estrogen-related drug, was widely prescribed to pregnant women to help prevent miscarriages. The daughters of these women face a higher risk for cervical cancer, genital tract abnormalities, and miscarriage. Environmental Chemicals. Long-term exposure to certain types of agricultural and industrial chemicals may increase the risk for cervical cancer. PrognosisThe following are some examples of the time it takes for early stages of cervical dysplasia to progress to the next stage:
Survival Rates in Women with Cervical CancerOver the past 30 years, the death rate from cervical cancer has declined significantly. In general, 71% of women with invasive cervical cancer survive for 5 years or more. African-American women tend to have poorer 5-year survival rates than Caucasian women, although survival rates have significantly increased in African-American women in recent years. The outlook for specific women varies depending on different factors:
Identifying what type of human papilloma virus (HPV) a woman has may help determine outlook and the severity of cervical cancer. For example, HPV-18 and HPV-16 are associated with severe cases. HPV-16 has also been linked to a rare form of cervical and uterine cancers. Other biochemical markers in the body may also help predict outcome and treatment. For example, women with cervical cancer who have high levels of an enzyme called cyclooxygenase (COX-2) may need more aggressive treatments than those with low levels. Consequences of TreatmentsThe treatments for advanced cervical cancer also add to the emotional burden in premenopausal women, because they nearly always prevent future childbearing. SymptomsMost women with dysplasia or pre-invasive cancer have no symptoms. Screening tests, therefore, are very important. When the cancer becomes invasive, unusual bleeding can occur. Bleeding may stop and start again between regular periods or there may be bleeding after menopause. Unexpected bleeding can also occur after intercourse or a pelvic exam. Periods sometimes last longer or are heavier than usual. Increased vaginal discharge may be noticeable as well. Pelvic pain can occur, but it is not common. These symptoms are not exclusive to cervical cancer. Sexually transmitted diseases, for instance, can cause similar symptoms. PreventionThe best way to prevent cervical cancer is to avoid getting infected with human papilloma virus (HPV). Because HPV is sexually transmitted, practicing safe sex and limiting the number of sexual partners can help reduce risk. A vaccine can protect against the major cancer-causing HPV strains. Regular Pap tests remain the most effective way of preventing the development of invasive cervical cancer. Vaccines against human papilloma virusIn 2006, the FDA approved the first human papilloma virus (HPV) vaccine to prevent cervical cancer. Gardasil has been tested in more than 12,000 uninfected girls and women in 13 countries. Studies show it provides nearly 100% protection against HPV-16 and HPV-18, the viruses that cause 70% of cases of cervical cancer. Gardasil also protects against HPV-6 and HPV-11, which cause 90% of cases of genital warts. Gardasil is approved for girls and women ages 9 - 26. Current immunization guidelines recommend:
The HPV vaccine can only prevent -- not treat -- HPV infection, genital warts, and cervical cancer. Because the vaccine cannot protect females who are already infected with HPV, doctors recommend that girls get vaccinated before they become sexually active. Several 2007 studies indicated that the vaccine is nearly 100% effective in preventing cervical cancer and genital warts when given prior to HPV exposure. However, young women who are sexually active may still derive some benefit from the vaccine, at least for protection against any of the four HPV strains that they have not yet acquired. The FDA is considering approving another type of cervical cancer vaccine (Cervarix). Cervarix protects against HPV-16 and HPV-18, as well as the cancer-causing strains HPV-31 and HPV-45. It does not protect against genital warts. The FDA is not yet sure how long Gardasil’s protection lasts or when patients may need a booster shot. A 2006 study of the Cervarix vaccine found that protection lasted for at least 4.5 years. These vaccines do not protect against all types of cancer-causing HPV. The FDA still recommends that women receive annual screening to detect any early signs of cervical cancer. For girls and women who have been sexually active before they receive the vaccine, screening still provides the best protection against cervical cancer. Use of Barrier ContraceptivesUse of barrier contraceptives such as condoms is associated with a reduced risk of cervical cancer, even in women already infected with human papilloma virus (HPV). HPV can exist outside the area protected by the male condom, so this method is not foolproof in preventing an initial infection. However, a 2006 New England Journal of Medicine study found that when men used condoms every time they had sexual intercourse, their female partners had less than half the rate of HPV infection as women whose partners used condoms less than 5% of the time. The female condom is becoming increasingly popular in developing countries. It may prove to be particularly effective against sexually transmitted diseases in these regions. Male CircumcisionA 2002 study reported that men who are circumcised have a lower risk for carrying human papilloma virus (HPV) and therefore reduce the risk for cervical cancer in their female partners. VitaminsSome studies have suggested possible protective benefits against cervical cancer from certain vitamins.
 Although vitamin E is a fat-soluble vitamin, there are no known toxic effects of mega doses.  Click the icon to see sources of food which contain vitamin E.  Click the icon to see the benefits of vitamin C.  Click the icon to see sources of food which contain vitamin C.
There is no definitive evidence, however, that taking vitamins can prevent any cancer. Eating healthy foods rich in such vitamins and other important nutrients is, in any case, the best approach for overall good health. DiagnosisThe changes that lead to cervical cancer develop slowly. Screening tests performed during regular gynecologic examinations can detect early changes. Pap SmearEvery year in the U.S. about 50 million women have a Papanicolaou test (the Pap smear). Use of the Pap smear has reduced the annual death rate from cervical cancer from 26,000 in 1941 to 3,700 in 2005. Forty percent of women who have a Pap smear fail to follow-up for retesting and treatment. Most cases of cervical cancer occur in women who have not had regular Pap tests. The Procedure. The most accurate test results are obtained 12 - 14 days after menstruation begins. Women should not douche or have intercourse within 48 hours of the test. Douches and spermicidal creams may clean out abnormal cells and interfere with the results of a Pap smear. (In general, douching is not recommended at all.) A Pap smear is usually painless, although some women may have some discomfort.
 A Pap test is a simple, relatively inexpensive procedure that can easily detect cancerous or precancerous conditions. Reliability and Accuracy. Over the course of a lifetime of regular screening, a woman faces a 40% chance of being told her Pap smear is abnormal. The Pap smear is not, however, a perfectly reliable measure of a woman's risk for cervical cancer. In general, about 10% of Pap smears have abnormal results, but only about 0.1% of the women who have these results actually have cancer. In most cases, abnormal cells are low grade and not likely to progress to cancer or are due to benign conditions, including natural cell changes after menopause. No test is 100% accurate, and it is possible for the Pap smear to miss the presence of cancer. However, if abnormal cells are missed on one test they are likely to be spotted during the next one without a significant danger. Liquid-Based Pap TestNewer, thin-layer liquid based tests (ThinPrep, SurePath) use the original cervical sample, which is rinsed in a special solution to thin the mucus (rather then dried). The result is a clear, clean sample that may be able to accurately reveal abnormal cells. The fluid can also be examined for evidence of human papilloma virus (HPV) and other early abnormalities. Some -- but not all -- studies have found this test to be more accurate than the standard Pap smear. A rigorous 2006 review of 56 studies found that liquid-based tests were no more accurate than conventional Pap smears. Current Pap Smear Screening RecommendationsThe U.S. Preventive Service Task Force (USPST), the American Cancer Society (ACS), and the American College of Obstetricians and Gynecologists (ACOG) have all released guidelines for cervical cancer screening. ACOG and ACS have established separate screening criteria for women below and above 30 years of age. Although there are some small differences between these three sets of guidelines, they generally make similar recommendations as summarized below: Recommendations for Initial Screening. Women should begin to undergo Pap tests within 3 years of onset of sexual activity or at age 21 (whichever comes first). Women with no history of sexual activity should still have Pap smears. They are at low risk for squamous cell carcinoma, but adenocarcinoma (cancer that occurs in cervical glands) can occur, although this is very uncommon. Women Up to Age 30. Women under age 30 should receive annual screening with the conventional Pap smear. The American Cancer Society (ACS) offers the alternative of screening every 2 years using the newer liquid-based testing. HPV testing is not recommended for this age group because HPV infections in women under age 30 tend to resolve on their own. Women Age 30 and Over. Women in this age group who have received three consecutive negative (normal) annual Pap tests have two screening options:
Elderly Women. In its 2003 guidelines, the U.S. Preventive Service Task Force recommended against routine screening in women over age 65 with low or no risk factors. (The ACS recommends stopping at age 70, while the American College of Obstetricians and Gynecologists declines to set an upper age limit.) Such women have had at least three previous normal screenings and have had no abnormal results for at least 10 years. According to the guidelines, older women should be screened if they have not been screened before or if there is a possibility that they have not been screened (for example, if the woman is from a country that does not do routine screening). However, a 2006 study of more than 15,000 postmenopausal women recommended continued screening for elderly women who are sexually active but not monogamous. (Women in the study had a uterus.) The researchers note that about 25% of new cervical cancer cases, and 41% of cervical cancer deaths, occur among women 65 years and older. After a Hysterectomy. The 2003 guidelines recommend against routine screening for women who have undergone a total hysterectomy for benign causes. Women who have had a hysterectomy that preserves the cervix (called a supracervical hysterectomy) should continue with Pap screening. Follow-up After Normal ResultsIf Pap smear results are normal for 3 consecutive years, most expert groups recommend a Pap test every 2 - 3 years thereafter in most women over 30 years of age. (The American Cancer Society suggests that such women wait until they are 30 before extending the interval to 3 years.) Both the American Cancer Society and the American College of Obstetricians and Gynecologists recommend that annual screening should continue in women in high-risk categories. High risk categories may include the following, depending on the medical group:
Follow-up After Abnormal ResultsAny abnormal result, even a mild abnormality, requires follow-up visits and additional tests. The extent of these tests depends on the degree of abnormalities. Computerized Pap Test SystemsNew tests and methods have been developed to improve the accuracy of the Pap smear in detecting cancer cells. For example, there are several computerized Pap test systems (FocalPoint, PAPNET) that are used to rescreen the original smear. These systems are either used to detect abnormal samples that may have been missed by manual review methods or are used in place of a human cytotechnologist. According to the U.S. Preventive Services Task Force (USPSTF), there is not yet enough evidence to know whether or not computerized methods are superior to conventional Pap testing. Tests for Human Papilloma VirusThere are tests for identifying the high-risk types of human papilloma virus (HPV) that are known to cause cervical cancer. The presence of these types is a strong predictor of high-grade aggressive abnormalities or cancer itself. Testing for HPV does not replace the Pap smear, but when used adjunctively with the Pap test this screening combination may help to more accurately detect cervical cell abnormalities than either test alone. In 2003, the FDA approved the Hybrid Capture 2 (HC2) HPV DNA test for use with the Pap test for cervical cancer screening in women over 30 years of age. The HPV DNA test can identify 13 types of the high-risk HPV that are most frequently implicated in the development of cervical cancer. At this time, the test is recommended as an adjunct to the Pap test but not as the sole method for primary screening. Other Screening TestsOther screening tests are being investigated for use in combination with the Pap smear for improving accuracy. For example, combinations with human papilloma virus (HPV) DNA tests or cervicography may prove to be more effective for detecting cervical intraepithelial neoplasia I and II dysplasia (potentially invasive cells) than Pap smears alone. Cervicography. Cervicography uses a photograph of the cervical region (a cervigram), which is then highly magnified and examined. It may prove to be a useful companion to a Pap test, particularly in high-risk younger women. It is painless, easy to use, provides documentation of the area, and is highly sensitive to abnormal changes. (It also, however, picks up abnormalities that are not cancerous.) Acid Test. A diluted solution of acetic acid (similar to vinegar) is applied to the cervix. When viewed through a special green lens, this solution makes abnormal cells look white, whereas normal cells appear pink. Skilled doctors may also be able to spot abnormal blood vessel patterns indicative of cancer areas on the cervix. This is an inexpensive and simple test. Fluorescence Spectroscopy. Small noninvasive probes that can be swept across the surface of the cervix to detect cancer are showing promise as an effective screening tool for cervical cancer. One probe emits a laser light. The head of the probe catches the return signals from the woman's cervical cells and compares them with a computer library of cancer cells. In one comparison test, fluorescent spectroscopy was more accurate than the Pap smear but not as effective as other screening methods. Other Investigative Tests. Experts are working on an antibody-based method for improving the identification of true cancerous cells in a cervical smear, which could significantly reduce the need for expensive and distressing tests in women who do not actually have cancer. In addition, they are looking for biologic markers to improve diagnosis, such as specific proteins that indicate the presence of cancer cells. Classifying Cervical Cells and Determining Further TestingThe cells viewed in a cervical smear sample are classified on a scale representing the spectrum of cell changes from normal to cancerous. The smear is first characterized as either "normal" or "abnormal." Once abnormal cells are identified, the doctor must decide whether the patient needs only repeat Pap smears, a test for the human papilloma virus (HPV) virus, or colposcopy (a procedure used to magnify the cervix and permit detection of lesions for biopsy). To help the doctor make the decision, the abnormal cells are divided into categories, depending on the degree of abnormality. These classifications are based on the 2001 Bethesda System (TBS), which is formulated to standardize the reporting of Pap test results. Atypical Squamous Cells. Atypical squamous cells (ASC) are mildly abnormal cells on the surface of the cervix. They may simply represent inflammation. Over 80% of these cells normalize, but unfortunately, between 5 - 17% of these women have a chance for having cervical intraepithelial neoplasia II and III dysplasia (potentially invasive cells). Researchers have further categorized atypical squamous cells as the following:
Among those with atypical squamous cells, immunosuppressed women and those with high-risk human papilloma virus infections are at higher risk for cervical intraepithelial neoplasia II and III and should always be given colposcopy. Postmenopausal women with normal immune systems have a lower risk than younger women. It should be strongly noted, however, that actual risk for cervical cancer in general in women with atypical squamous cells is only 0.1 - 0.2%. Low Grade Squamous Intraepithelial Lesions. Low-grade squamous intraepithelial lesions (LSIL) are typically associated with human papilloma virus changes, with or without early dysplasia. Between 15 - 30% of women with LGIL, however, may have cervical intraepithelial neoplasia II or III on biopsy. Women with LSIL are either monitored with repeat Pap smears or given colposcopy. Doctors recommending colposcopy argue that these are high-risk women who risk delaying a diagnosis of cancer using only repeat Pap smears. High-Grade Squamous Intraepithelial Lesions. High-grade squamous intraepithelial lesions (HSIL) are associated with moderate dysplasia and other cervical intraepithelial neoplasia II or III. Such women are always referred to colposcopy for biopsy. Even if colposcopy results report only cervical intraepithelial neoplasia I, over a third of these women are likely to have cervical intraepithelial neoplasia II or III. Experts, therefore, recommend a careful review of the tests in such cases. Pregnancy poses a problem since it increases the chance in HSIL for both normal and abnormal results. In nonpregnant women, particularly when fertility is not an issue, immediate treatment with loop electrosurgical excision procedure may be appropriate. Atypical Glandular Cells. Atypical glandular cells are uncommon, but pose a higher risk for cancerous changes than atypical squamous cells or low-grade squamous intraepithelial lesions. Between 9 - 54% have some cervical intraepithelial neoplasia, 0 - 8% have pre-invasive cancer, and 1 - 9% have invasive cancer. Doctors recommend that the next step should be a colposcopy (rather than a repeat Pap smear). Colposcopy and BiopsyThe Pap smear shows only the presence of abnormal cells. It is useful simply as a screening test that identifies women who may have preinvasive or early cancerous changes. For a definitive diagnosis, the next step is usually colposcopy, during which the cervix is visualized under low power magnification. The surgeon takes samples of suspicious cells for biopsies. A biopsy will determine the stage of the precancerous growth or whether invasive cancer is present. The Procedure. Colposcopy can be performed in a doctor's office without anesthesia in 10 - 15 minutes. It causes about as much discomfort as mild menstrual cramps:
 Click the icon to see an image of a colposcopy-directed biopsy. After the colposcopy, the woman may have a brownish discharge from an iron solution called Monsel's solution, which the doctor applies to prevent bleeding. The doctor usually advises sexual abstinence for 1 - 2 weeks. Follow-Up Procedures. Women with evidence of cervical intraepithelial neoplasia (CIN) or cervical cancer require treatment. Women with biopsies that show low-grade abnormal cells (LGSIL), but whose cervix is otherwise normal, are generally given follow-up colposcopies. Treatment for Cervical Intraepithelial Neoplasia and Pre-invasive CancerTreatment of cervical intraepithelial neoplasia (CIN), including pre-invasive cancer, depends on the type and extent of abnormal changes. Some of the treatments for CIN are also used for early-stage cancer.
 The cold cone biopsy is a surgical procedure that requires general anesthesia. It is performed when there are severe precancerous changes in the cervix. Treatment for Adenocarcinoma. An adenocarcinoma is cancer inside tissue that looks like or functions as a gland. (A gland is a group of cells that secretes a substance to be used by or removed from the body.) Adenocarcinomas tend to be more aggressive than the more common pre-invasive cancer, which grows in the lining of tissue (mucous membrane). Some evidence suggests that adenocarcinomas develop in numerous sites rather than a single location. Hysterectomy is generally recommended. For women who wish to retain fertility, a doctor may perform a cone biopsy, although this procedure sometimes causes sterility and it does not always remove all adenocarcinomas. Follow-Up. Patients treated for CIN need to be monitored. Testing for human papilloma virus (HPV) may prove to be useful in determining whether repeat colposcopies may or may not be needed. One study strongly suggested that if both HPV and Pap smear tests are normal on two consecutive visits, treatment most likely was successful. If either the HPV or Pap smear is abnormal, it may be reasonable to consider another colposcopy. Loop Electrosurgical Excision ProcedureLoop electrosurgical excision procedure (LEEP), also called large loop excision of the transformation zone (LLETZ), uses a high frequency electrical current to cut away diseased tissue.
The procedure is done in one office visit. Extensive and deep sections of damaged tissue can be effectively removed in this visit. Disease can be cured in one treatment. When used for dysplasia, it appears to be as effective as more invasive procedures. The only downside of LEEP may be its simplicity. Doctors may be tempted to use it for more serious conditions best treated by a procedure called conization. It also may impair the ability to detect hidden invasive cancer. Patients should be monitored closely if the biopsies on the cervical tissue removed by LEEP suggest that the cells may become invasive. LLETZ is becoming increasingly popular as a treatment for cervical intraepithelial neoplasia. However, women of child-bearing age should be aware that it may later cause pregnancy problems, such as preterm delivery and low birth weight. Women who have this procedure may also be more likely to break their water too early (premature rupture of membranes). ConizationConization is a surgical procedure that removes suspicious sections of cells covering an abnormally large area, or those extending into the cervical canal. Conization is preferred over Loop electrosurgical excision procedure (LEEP) or large loop excision of the transformation zone (LLETZ) for lesions that are so big they require a larger biopsy for their complete removal. As in LEEP, patients should be monitored closely if patients are infected with human papilloma virus (HPV) virus or the biopsies on the cervical tissue removed show aggressive-grade cells. The surgery can be performed under general anesthesia in the operating room with either traditional surgical instruments or lasers. A technique called frozen section examination (FSE) freezes the margins of the area being removed. Studies suggest that FSE allows immediate and precise evaluation of areas that may harbor invasive cancer cells, and may be an important addition to this procedure in women with high-grade cervical intraepithelial neoplasia. With conization, the ability to become pregnant can be preserved in many (but not all) cases. In women who do become pregnant, some studies have indicated that this procedure increases the risk for low-birth weight infants, so careful prenatal care is essential. Conization can also increase the risk for preterm delivery and Cesarean section. Patients who have this treatment must have follow-up evaluations. CryosurgeryCryosurgery is not usually feasible for large abnormal areas. The procedure removes abnormal, but noncancerous, tissue by freezing it. Cryosurgery can be performed in a doctor's office in 15 minutes without medication.
 Click the icon to see an image of cervical cryosurgery. Side effects from this procedure include cramping, sometimes painful, for a few hours or days and a heavy, watery discharge for 2 - 4 weeks. The discharge can be irritating, have a bad odor, and may be blood-tinged. Symptoms that may indicate serious complications are fever and chills, heavy clotted bleeding, or extreme pain in the abdomen or back. The patient may have a temporary change in menstrual periods. The menstrual periods may be heavier or lighter, or come later or earlier. Tampons, douching, bathing, swimming, and intercourse should be avoided for several weeks after cryosurgery to prevent infection. Patients who have this treatment must be willing to commit to regular follow-up examinations. Treatment for Cervical CancerIn contrast to cervical intraepithelial neoplasia, cervical cancer represents true invasion of cells beyond the epithelium into surrounding tissue. Cervical cancer may be detected in a biopsy performed during colposcopy for an abnormal Pap smear, or it may be visible to the naked eye when the doctor performs a speculum exam. Imaging Tests to Determine Extent of Tumor Spread. If a biopsy detects invasive cancer, the patient will need additional tests to find out how far the cancer has spread. How fart the cancer has spread determines whether the cancer is operable.
 In computed tomography (CT), a thin x-ray beam rotates around the area of the body. Using very complicated mathematical processes called algorithms, a computer is generates a 3-D image of a section of the body.
 Click the icon to see an image of intravenous pyelography.  Click the icon to see an image of a barium enema. If these tests detect cancer in any of these surrounding sites, the patient will need more tests :
 Click the icon to see an image of cystoscopy.
 Click the icon to see an image of sigmoidoscopy.
 Click the icon to see an image of a MRI. Sentinel Node Biopsy. One technique is called a sentinel node biopsy. It has been used in patients with breast cancer to help determine if cancer has spread beyond the lymph nodes. It is now being investigated for patients with early cervical cancer and may be helpful in determining which patients need to have lymph nodes removed in their pelvic area:
General Treatment GuidelinesAfter making a diagnosis, the doctor will classify the stage of the cancer according to how far the disease has spread into the lining of the cervix, throughout the cervix, or beyond. Doctors use these classifications to determine treatment and outlook. Patients who have been diagnosed with cervical cancer need to know the normal treatments for their particular stage, so they may compare their doctor's suggestions with these norms. Stage 0 and TreatmentsStage 0 is pre-invasive cancer confirmed by biopsy and confined to the first layer of cervical tissue (the epithelium). Treatment options include loop electrosurgical excision procedure (LEEP), laser therapy, conization, and cryotherapy. Stage I (Including Locally Advanced Cancer) and TreatmentsStage I is invasive cancer, but the tumor is confined to the cervix. This stage is further categorized as IA and IB. Stage IA. Five-year survival rates for stage IA can be 95% or more.
Note on Stage IA2 through IIA: Postoperative concurrent radiation and platinum-based chemotherapy may be considered for stages IA2 through IIA tumors if the following high risk features are found at the time of primary surgery: lymph node involvement, cancerous cells found in the margins of the tumor, and involvement of the parametrium. Stage IB and Locally Advanced Cancer. Five-year survival rates for stage IB can be 80 - 90% with either radiation or surgery. Survival rates are lower if the cancer has spread to the lymph nodes.
Note on Locally Advanced Cervical Cancer: Stages IB2 through IVA are often referred to collectively as locally advanced cancer and are frequently treated similarly. Standard treatment includes radiotherapy with concurrent platinum-based chemotherapy. Experimental approaches for some women with locally advanced cervical cancer use radiation therapy with hyperthermia (high heat often provided by ultrasound) and neoadjuvant (preoperative) chemotherapy and radical surgery. More research is necessary. Stage II and TreatmentsStage II invasive cancer has spread beyond the cervix, but it has not spread to the pelvic side wall. This stage is further categorized as IIA and IIB. Stage IIA. Cure rates for stage IIA can be as high as 75 - 80% with either radiation or radical hysterectomy. Survival rates are lower if cancer has spread to the lymph nodes. In stage IIA, cancer has spread to the upper two thirds of the vagina but not to the parametrium (the connective tissue between the pelvic floor and upper part of the cervix). Radical hysterectomy with pelvic lymph node removal (lymphadenectomy) is the recommended treatment. Primary radiation can be used instead of surgery in patients who eitehr are poor surgical candidates or do not plan on being sexually active. If the tumor is bulky, however, primary treatment with radiation therapy with concurrent platinum-based chemotherapy is reasonable. Some women in stage IB may receive combinations of radiation and surgery. Stage IIB. For stage IIB 5-year survival rates are about 60%. In stage IIB the cancer has spread to the parametrium. Recommended treatment is radiation therapy with concurrent cisplatin-based chemotherapy. Stage III and TreatmentsIn stage III, the cancer is invasive, extending to the lower third of the vagina (stage IIIA) or to the side walls of the pelvis (stage IIIB). The kidney may be affected. Recommended treatment is radiation therapy with concurrent cisplatin-based chemotherapy. Five-year survival rates are about 40%. Stage IV and TreatmentsIn stage IV, invasive cancer has spread beyond the pelvis or to the mucosal lining of the bladder or rectum. Five-year survival rates are less than 20%. Stage IV. In stage IVA, the cancer has spread to the inner lining of the bladder or rectum. Recommended treatment is radiation therapy with concurrent cisplatin-based chemotherapy. Stage IVB. In stage IVB, the cancer has spread beyond the pelvis. Recommended treatment is radiation therapy to relieve symptoms and chemotherapy (usually cisplatin or carboplatin combined with other drugs such as topotecan). Platinum-based chemotherapy yields short-lived response in 20% of patients. Clinical trial participation is reasonable. Recurrent or Persistent Cancer and TreatmentsCervical cancer may recur locally in the lymph nodes near the cervix, it may spread to distant sites, such as the lung or bones, or it may appear both locally and in distant locations. Recommended treatment is pelvic exenteration if cancer has spread to only local areas. (This involves removal of the cervix, uterus, vagina, and perhaps the bladder, lower colon, or rectum. It is an aggressive surgical approach that may lead to cure in a small percentage of patients with recurrent cervical cancer.) Radiotherapy is another option if it is technically possible -- generally if patients did not have it previously. If cancer has spread, platinum-based chemotherapy is reasonable. Other drugs may be useful under certain circumstances. Treatment of Pregnant Women with Cervical CancerOnly 1% of cervical cancers occur during pregnancy or shortly afterwards. To diagnose the condition, a cervical biopsy, in which a small amount of tissue is removed for diagnosis, can be performed anytime during the pregnancy. However, a cone biopsy, which removes larger amounts of tissue, is typically delayed until after the first trimester to reduce the risk of abortion. Treatment options may be as follows:
Treatment for Invasive Cervical CancerRadiation therapy and surgery are about equally effective as a single option for treating very small cervical cancers in their earliest stages. Survival rates in the appropriate patients can be about 85 - 90%. Factors influencing the choice between radiation therapy and surgery in women with invasive cancer include the patient's age and health and the amount of cancer. Both surgery and radiation therapy eliminate the possibility of having children in premenopausal women. Although treatments for cervical cancer have several potentially severe side effects, they are usually well-tolerated. Women undergoing any of these treatments should feel free to seek support groups and counseling, which can be as important for their outlook as medical therapies. Choosing Between Surgery or Radiation in Early-Stage CancerSurgery. Surgery almost always involves a hysterectomy, an operation that removes the uterus and sometimes other areas in the pelvic region as well. It does not, however, usually impair sexual activity. In general, surgery is the better choice when small cancers are confined to the cervix in women who wish to remain sexually active. Radiation. Radiation treatments to the pelvis often inhibit ovarian function. Early menopause often occurs. Radiation also may cause vaginal scarring. Treatments are available that may reduce these problems, and women should not be shy about discussing them with their doctor. Radiation therapy is usually the choice under the following circumstances:
Important studies now strongly suggest that radiation along with chemotherapy can improve survival rates improve in patients with stages IB to IVA compared to radiation alone. The benefits are greatest in stages I and II. SurgeryIn the early stages of cervical cancer, surgery is often the preferred primary treatment approach since it preserves normal sexual function. Some patients desiring fertility who have early stage I cancer may be candidates for cervical cone biopsy. Hysterectomy. A hysterectomy attempts to eliminate the cancerous tissue by removing the uterus. There are several variations of this operation, depending on the location of the tumor. In women of childbearing age, the ovaries can usually be left intact. Although a woman who has a hysterectomy but retains her ovaries cannot bear children, she will not go into premature menopause. (Studies indicate that leaving the ovaries intact is safe for most women and does not pose any greater risk for cervical cancer recurrence.) A simple hysterectomy involves the removal of the uterus and the cervix, but leaves the parametrium (tissue surrounding the uterus) and vagina intact. Lymph nodes in the pelvis are not usually removed.  Click the icon to see an illustrated series detailing a hysterectomy. A radical hysterectomy removes not only the uterus and the cervix but also the parametrium, the supporting ligaments, the upper vagina, and some or all of the local lymph nodes (a procedure called lymphadenectomy). If the cancerous tumor recurs within the pelvis after primary treatment, the patient may need a more extreme procedure called a pelvic exenteration, which combines radical hysterectomy with removal of the bladder and rectum. (In such cases, plastic surgery may be needed afterward to recreate an artificial vagina.) Patients undergoing this procedure are physically and psychologically screened in advance to determine whether it is an appropriate choice. The success rate for pelvic exenteration in halting the progression of the disease is about 25 - 45%. Any form of hysterectomy is major surgery and requires at least a 3 - 5 day hospital stay. Although hysterectomy typically uses a wide abdominal incision, less invasive techniques that allow shorter recovery time may be possible for some women with early stage cancers if performed by experienced surgeons. Side effects include difficulty emptying the bladder or bowels and a painful lower abdomen. Urinary tract infections are very common. Complications include fistulas (abnormal channels within the pelvis, which in this case are a result of surgery), bladder dysfunction, and cysts. Normal activity, including intercourse, can be resumed in about 4 - 8 weeks. Once the uterus is removed, menstruation will cease. If the ovaries are removed, the symptoms of menopause will begin. These symptoms are likely to be more severe in surgical menopause than in natural menopause. The patient should discuss the benefits and risks of hormone replacement therapy with her doctor. Trachelectomy. An experimental procedure called trachelectomy is being investigated for preserving fertility in certain women in early-stage cervical cancer, but it is highly controversial and appropriate in only about 5% of patients. In the procedure, only the cancerous portion of the cervix is removed, while the uterus and the rest of the cervix are left intact. The cervix is closed with a suture. The procedure is primarily performed outside the U.S., and few American surgeons are skilled in this surgery at this time. Throughout the world, in fact, only about a few hundred of these procedures have been performed to date. Larger and longer-term studies are needed to confirm its long-term safety. RadiationRadiation therapy is an alternative approach for early stage cervical cancer. Radiation with concurrent cisplatin-based chemotherapy is now the standard treatment for locally advanced cervical cancer. Radiation therapy uses high-energy rays aimed at the body from an outside machine (external beam radiation) and radioactive materials placed inside the body against the cervix (intracavitary radiation).
In order to be effective, radiation therapy must be powerful enough to destroy the cancer cells' capacity to grow and divide. This means that normal cells are also affected, which may cause significant side effects. Fortunately, healthy cells usually recover quickly from the damage, whereas abnormal cells do not. Advanced methods that target radiation more precisely and limit the damage to healthy tissue are now available. They include 3-D conformal radiation and intensity-modulated radiation therapy (IMRT):
Side Effects. Side effects of radiation therapy include fatigue, redness or dryness in the treated area, diarrhea, frequent or uncomfortable urination, and vaginal dryness, itching, or burning. After treatment, side effects usually disappear. Long-Term Complications. Complications include proctitis (inflammation of the rectum) and cystitis (inflammation of the bladder). Bowel obstruction is an uncommon complication. Radiation therapy may also cause vaginal scarring, sexual difficulties, and premature menopause in younger women. Occasionally an abnormal tunnel between the bladder and the vagina, known as a vesicovaginal fistula, will develop and may require surgery.  Click the icon to see an image of the female anatomy. Investigative temporary silicone implants or a noninvasive device called the belly board may protect the small intestine during radiation therapy and help reduce complications. Radiation itself may increase the risk for later development of cancer in the area surrounding the treated tissue. Although newer more precise radiotherapy approaches should reduce this risk, there is some concern that IMRT may double the incidence of secondary cancers over time compared to 3-D conformal techniques. This is of particular concern in younger patients. Radiation and Hyperthermia. Investigators are studying hyperthermia (use of high heat often provided by ultrasound) in combinations with radiation therapy. This approach has shown some promise in achieving significant response rates in small studies. Comparison studies are important to determine if this approach would be as beneficial with radiation therapy as concurrent chemotherapy. ChemotherapyChemotherapy uses cell-killing drugs called cytotoxic drugs to destroy widespread cancer cells that have spread from the primary tumor and can no longer be treated with surgery or radiation. For many years, chemotherapy was only used to reduce symptoms in women with very advanced disease. Today, platinum-based chemotherapy drugs (see below) are being used in many situations for cervical cancer, such as:
Platinum-Based Drugs. Platinum-based drugs cisplatin and carboplatin are often used for treating various stages of cervical cancer. These drugs are usually used in combination with radiation therapy or other chemotherapy drugs. In 2006, the FDA approved a combination of cisplatin and topotecan (another type of chemotherapy drug) for treatment of late-stage cervical cancer in women who are unlikely to be helped by surgery or radiation therapy. Women with stage IVB cervical cancer who received the combination treatment survived around 3 months longer (9.5 months versus 6.5 months) than women who received only cisplatin. Other drugs. Other drugs, mostly used in combinations, have also been investigated with some promise. They include epirubicin, irinotecan, paclitaxel, bleomycin, mitomycin, vinorelbine, gemcitabine, and doxifluridine. Administration. Chemotherapy may be given by mouth or as an injection. This may be done at a medical center, doctor's office, or even a patient's home. Some patients receiving chemotherapy may need to remain in the hospital for several days so the effects of the drugs can be monitored. The drugs are often given in cycles with a period of rest following a period of treatment, to allow recovery from the side effects. Side Effects. Chemotherapy affects all fast-growing cells, including healthy ones. So, side effects are inevitable. Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Common side effects include the following:
Complications. Serious short- and long-term complications can also occur and may vary, depending on the specific drugs used. They include:
Resources
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9/1/2006 Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-
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