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Incidence and Survival Anatomy Cervical Dysplasia or Cervical Intraepithelial Neoplasia Cervical Cancer Rare Types of Cervical Cancer Who is at Risk? Cells in the body normally reproduce themselves in an orderly manner. In cancer, however, cells start dividing uncontrollably and do not die the way normal cells do. As the cells produce more cells, a mass or tumor may appear. The tumor can invade surrounding tissue and keep the healthy tissue from doing its normal job. There are two kinds of tumors:
If you are one of the millions of women who regularly visit their obstetricians and gynecologists for routine pelvic examinations and Pap tests, then you are part of the good news about cervical cancer. This disease is almost 100 percent curable when it is diagnosed in its early stages and treated promptly. The key word here is "early," which is why experts recommend that every woman have regular Pap smears and pelvic exams. Pap smears are the single most effective method for identifying irregularities in cervical cells that could develop into cancer. After the Pap smear was introduced in the 1940s, the death rate for cervical cancer started to fall. Between 1955 and 1994, the death rate fell by 75%, and it continues to fall at a rate of about 4% per year. Cancer of the cervix is the third most common gynecologic cancer in the US after cancers of the endometrium and ovary. The American Cancer Society estimates that 11,270 women in the United States will be diagnosed with invasive cervical cancer in 2009 and as many as 4,070 women will die from the disease (ACS Cancer Facts & Figures, 2009). Many of these deaths could be prevented with regular screening and early treatment. Worldwide, over 555,000 new cases of cervical cancer were expected for the year 2007, and nearly 310,000 deaths were expected to occur from it. Approximately 85% of the new cases and 88% of the deaths were projected to occur in developing countries where cervical cancer is the second most common cancer in women. In developing countries, cervical cancer is the number 1 cause of cancer deaths in women (ACS Global Cancer Facts & Figures, 2007). This is in part due to the lack of access to screening for cervical cancer. With more advanced cervical cancer, radiation therapy, chemotherapy, or both can be used alone or in combination with surgery. However not all cervical cancer responds to radiation therapy or chemotherapy. In addition, disease returns in approximately one-third of all women treated for advanced cancer, usually within two years of therapy. Recurrent cancer after treatment is most commonly found in the cervix, the uterus, upper vagina, and the pelvic wall. Cancer that returns after hysterectomy usually is found in the upper part of the vagina, where the cervix used to be located. These symptoms indicate possible recurrence: weight loss, unexplained swelling in one or both legs, bloody vaginal discharge, and pain in the thigh or buttock. When advanced cancer recurs in the pelvic area, prognosis is generally favorable. If the cancer has spread to locations beyond the pelvic area, however, the chances for recovery are less favorable. Once a diagnosis of cervical cancer has been made, it is important to know your options when considering treatment for CIN or cervical cancer. Talk with your doctor. Find out exactly why he or she is recommending certain treatments or tests. When reviewing the consequences of major surgery or radiation, don't lose sight of the risk associated with doing nothing. Stay well informed and you'll make the choice that's best for you and your family. Anatomy 
A little more than an inch long, the cervix is the narrow end of the uterus that opens into the upper part of the vagina. In pregnancy, the cervix helps hold the uterus closed. Several weeks prior to labor and childbirth, the cervix thins and begins to expand, or dilate. At delivery, the cervix opens completely to allow the movement of the baby through the birth canal. The bulk of the cervix, or stroma, is formed by connective tissue. This is covered by a surface layer called the epithelium. The epithelium is made up of two different types of cells. The epithelium of the endocervical canal (the inner surface of the cervix) is comprised of tall glandular cells that produce cervical mucus. The epithelium on the outer aspect of the cervix that can be seen at the top of the vaginal canal (the ectocervix) is formed by layers of flat, disc-like cells called squamous cells. The area where the squamous cells meet the glandular cells is called the transformation zone. The transformation zone is the area that is most susceptible to the changes that can lead to cancer. Cancer that resembles the squamous cells is called squamous cell carcinoma. That that resembles the glandular cells is called adenocarcinoma. Of all invasive (invading neighboring tissue) cervical cancers that are diagnosed, roughly 80-90 percent are squamous cell carcinomas and most of the remaining are adenocarcinomas. Several types of adenocarcinomas exist. Around 60% are endocervical adenocarcinomas, about 20% are adenosquamous (contain squamous-like elements), about 10% are endometrioid (resemble the cells that line the uterus), and about 10% are clear cell. Other, more rare cancers of the cervix include cervical sarcoma, neuroendocrine tumors, cervical melanoma, adenoid carcinomas, and glassy cell carcinoma. Cervical Dysplasia or Cervical Intraepithelial Neoplasia 
Also called cervical dysplasia, cervical intraepithelial neoplasia (CIN) is not cancer, but represents early changes on the surface of the cervix that may develop into cancer. Nearly half the time, cervical dysplasia will go away on its own. Pap tests can detect cervical dysplasia. However, no test can predict whether CIN will develop into cancer, which is why early detection and treatment of any abnormality is so important. When diagnosed, cervical intraepithelial neoplasia is graded as being low-grade, moderate-grade, or high-grade. It has been estimated that about 330,000 cases of high-grade dysplasia (CIN 2 or 3) and over 1 million cases of low-grade dysplasia (CIN1) are diagnosed in the US each year. It is most commonly diagnosed in women ages 25 to 35, but can develop at any age. Cervical Cancer Noninvasive carcinoma 
Early forms of cancer, when it remains contained within its original location without having spread in nearby tissues, are often referred to as noninvasive cancer or "in situ" cancer. In the case of these types of cancers, including cervical carcinoma in situ (or adenocarcinoma in situ if it is comprised of glandular cells), a thin layer called a basement membrane separates the culprit cells (the cervical epithelial cells) from the adjacent tissue (the cervical stroma). Eliminating cervical cancer while it is noninvasive makes a complete cure almost a certainty. Without treatment, however, carcinoma in situ often develops into invasive cervical cancer, where the basement membrane is penetrated and the stroma is affected. If the cancer goes untreated and becomes invasive, the odds of curing it decline rapidly. Population research has shown that cervical carcinoma in situ occurs most often in women between 30 and 40 years of age. Invasive cervical cancer 
By definition, invasive cervical carcinoma has penetrated the basement membrane. Once it has passed through the basement membrane, the cancer can grow into the stroma and then can continue to spread from there. Cervical cancer staging is based on how far the cancer has spread. Cancers that grow on the vaginal-facing surface of the cervix (the ectocervix) may appear as an ulcer and may have protruding components. Tumors that grow in the cervical canal (endocervix) may remain hidden from view, but can enlarge the cervix, causing it to become "barrel-shaped." Most women diagnosed with cervical cancer are under the age of 50, although nearly 20% of women diagnosed are over the age of 65. Cervical cancer is not common in women under the age of 20. Metastasis Cervical carcinoma may spread, or metastasize, by direct growth into the inner part of the vagina, the tissues around the vagina, cervix, and uterus (the parametrium), or into the body of the uterus. The cancer can also spread directly into the bladder and rectum. Another way the cancer can spread is through the lymphatic system, a network of vessels and glands that form part of the body's immune system. The closest lymph nodes are those of the pelvis. From there, the cancer can continue to spread via the lymphatic vessels to lymph nodes around the aorta (para-aortic nodes), the main artery that carries blood from the heart to the rest of the body, and on to more distant lymph nodes. Distant spread of the disease through the bloodstream is infrequent, but the most common sites are the lungs and the liver. Metastasis to the brain and bone is also possible, but not common. Although not a site for metastasis, the kidney can also be affected by the spread of cervical cancer. The kidneys rest behind the abdominal cavity on either side of the spinal cord near the base of the ribs. They are drained by long tubes called ureters that carry urine from the kidneys to the bladder, where it can be stored. As cervical cancer continues to grow in the pelvis, it can press on one or both ureters and ultimately block the flow of urine through the ureter. The kidneys and ureters are not designed to hold urine, and the pressure can cause the ureters to dilate and damage the delicate tissues of the kidney. Rare Types of Cervical Cancer Cervical sarcoma Cervical sarcoma accounts for less than one-half percent of cervical cancers. Sarcomas are tumors that originate in the stroma instead of the epithelium, or surface layer, of the cervix. Although surgery may be used for early stage sarcomas, the best way to treat them, especially when more advanced, is unclear. A few different types of cervical sarcomas exist. Adult cervical sarcoma botryoides resembles a cancer sometimes seen in children and may be treated with a combination of surgery and chemotherapy. Neuroendocrine tumors Neuroendocrine cervical cancer is also very rare. A small cell variety exists that resembles small cell cancer of the lung. It accounts for fewer than 3% of all cervical cancers. Early stages may be treated with surgery and radiation or chemoradiation (a combination of chemotherapy and radiation therapy). Generally, small cell neuroendocrine carcinoma has a poor prognosis. Carcinoid neuroendocrine tumors are also rare. In contrast to the small-cell cancers, the carcinoid tumors tend to be low-grade. Some experts classify the carcinoid tumors as a subtype of adenocarcinomas. Melanoma This type of the cervical cancer is also rare. It can be hard to determine if it originated in the cervix, in which case the cervix would be the "primary" site, or migrated (metastasized) from elsewhere in the body, in which case the melanoma of the cervix would be the "metastatic" site. Careful examination to determine the primary site is important. Melanoma of the cervix most often occurs in patients from 60-70 years of age. Most patients have no symptoms other than vaginal bleeding. Surgery tends to be the preferred treatment, but the prognosis is generally poor. Adenoid carcinomas There are 2 different types of adenoid carcinomas of the cervix, adenoid cystic and adenoid basal. Both may be classified as subtypes of adenocarcinomas, with adenoid cystic carcinoma comprising about 3% of adenocarcinomas and adenoid basal representing less than 1% of adenocarcinomas. Recognized as separate types of cancers in the 1960s, it is important to distinguish between the 2, as adenoid cystic carcinoma tends to be more aggressive and have a worse prognosis. In contrast, adenoid basal carcinoma tends to have a favorable prognosis. Both types of cancer tend to be most common in older women. Glassy cell carcinomas Cervical glassy cell carcinomas may also be classified as subtypes of adenocarcinomas. Glassy cell carcinomas are poorly differentiated. Differentiation is a process that cells undergo as they develop where their ultimate characteristics and functions are determined. A fully differentiated cell has a very specific purpose and is not able to change into other types of cells. Glassy cell carcinomas are considered high-grade and tend to have a poor prognosis. Who is at Risk? All women who have been sexually active are at risk for cervical dysplasia and cervical cancer. As with many other forms of cancer, researchers are unsure of the exact cause, although several factors have been identified that increase the risk. These risk factors are listed below. Human papillomavirus (HPV) It is now believed that most, if not all cases of cervical cancer are related to persistent infections with human papillomavirus (HPV) infections. There are over 100 different types of HPV. About 60 types cause common warts on skin surface, the other 40 types may be sexually transmitted and affect the genital and anal areas. HPV is thought to be the most common sexually transmitted disease in the United States. Only a few of the types that are transmitted sexually increase the risk of developing cervical cancer. About 70% of cervical cancers are caused by HPV 16 and HPV 18, although HPV 31, HPV 33, HPV 45, and a few others have been associated with it as well. Still, most women diagnosed with HPV never develop dysplasia or cervical cancer. It used to be thought that, although problems such as dysplasia caused by HPV could be treated, that HPV could not be "cured." However, many women who test positive for HPV test negative later on, frequently within 6 months to a year. It is not known if this means that the immune system has destroyed the virus completely, or if it has cleared enough that it is no longer detectable, but is still present. If the virus still remains, it is possible that it could reappear if the immune system were to be weakened. HPV usually does not cause symptoms, so it typically can only be detected with specific testing. If it is found, further investigations are typically used to help determine if treatment is needed. If no evidence of dysplasia or cervical cancer is found, aggressive treatment is not necessary, but regular follow-up is. Using condoms ("rubbers") during intercourse can help reduce the risk of infection with sexually transmitted diseases such as HPV. Even so, condoms do not offer complete protection because they do not cover all of the areas of the body that can potentially be infected with HPV, such as the skin of the genital and anal regions. One study showed that, when condoms were used correctly and every time that sex occurred, they could lower the infection rate by around 70%. Another option to reduce the risk of HPV infection is vaccination. Two vaccines have been developed to help prevent infection with the strains of HPV that are considered "carcinogenic." Both vaccines, known as Cervarix® [bivalent human papillomavirus (types 16, 18) recombinant vaccine] and Gardasil® [quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine], have been FDA-approved. In order for the HPV vaccine to be effective, it must be given before an infection is already present. It is currently recommended that the HPV vaccine should be a routine vaccination given to females aged 11 to 12; it may be give as early as age 9. Catch-up vaccinations have been recommended for women age 13 to 18. Some recommend that the catch up vaccination should also be given to women age 19 to 26, while others argue that research has not clearly shown that the benefit outweighs the risk for this age group. More studies are underway. While the vaccines protect against the HPV strains that cause most cancers, they do not protect against all HPV strains. Regular Pap smears continue to be recommended following immunization. Human immunodeficiency virus (HIV) HIV is the virus that causes the acquired immunodeficiency syndrome (AIDS). It can be transmitted through sexual contact, shared needles, and from mother to baby during pregnancy, delivery, or breastfeeding. The virus weakens the body's immune system, which seems to include its ability to fight HPV infection and potentially the cervical cancer that may result from it. Women who have HIV infections may experience a more rapid progression of dysplasia to cancer than women who do not have them. Annual Pap smears are recommended for women who have HIV regardless of the number of normal Pap smears they have had. Similarly, they are recommended for women who have a weakened immune system for other reasons, such as organ recipients on immunosuppressant drugs, women on chemotherapy for other types of cancer, and women who use steroids chronically. Cigarette smoking Smoking increases the risk of developing cervical cancer 2-fold. When women smoke, the toxins they inhale are absorbed in the lungs and can be transported throughout the body via the blood stream. Chemicals from cigarettes and cigarette smoke have been found in the cervical tissue of women who smoke. Scientists think these chemicals may damage cervical cells and weaken their ability to fight off infection, as well as make them more vulnerable to abnormal development. Although the exact mechanism linking cigarette smoking and cervical cancer has not been established, quitting smoking is recommended. Quitting smoking reduces risk of CIN (cervical intraepithelial neoplasia -- a noncancerous abnormality) and cervical cancer and improves overall health. Sexual behaviors that increase risk Women who have sexual intercourse at an early age may be more susceptible to cervical cancer than other women are. One theory for this risk is that the developing cells in the cervix of a young woman are more fragile than the cervical cells of older women, and more likely to be damaged from the slight abrasions caused by sexual intercourse. An increased risk for developing cervical cancer has also been seen in women who have multiple sexual partners. Exposure to multiple partners can occur directly, or indirectly through a partner who has multiple sexual contacts. Women with multiple partners have a greater chance of contracting sexually transmitted diseases. Teenagers are especially at risk for STDs, including human papilloma virus (HPV) and herpes. Some studies have shown an increased risk of cervical cancer in women with a history of chlamydia, which is an STD that often does not cause symptoms. Multiple pregnancies It is not clear why, but women who have had multiple full-term pregnancies seem to be at higher risk for cervical cancer. It is possible that they have had greater exposure to unprotected sex than women who have not had several pregnancies. It's also possible that some of the hormonal changes that a woman undergoes when she is pregnant might increase the risk of HPV infection, or that the risk of infection and growth of cervical cancer is increased due to a weakened immune system during pregnancy. Age The risk of cervical cancer increases with age. When first diagnosed, cervical cancer in older women tends to be more advanced. Few women over age 65 have Pap smears regularly. Furthermore, one research study reports that after age 44, women no longer listed the Pap smear as the major reason for visiting a physician's office. Some women mistakenly believe that once menopause begins, they no longer need routine gynecological exams. Women should continue regular exams and Pap smears regardless of age. Income Women in low-income groups develop cervical cancer five times as often as women in higher economic brackets do. One explanation for this discrepancy in cancer rates is that poor women are less likely to have regular access to cancer screenings and follow-up care. Race While rates of cervical cancer have been falling in African Americans and Hispanics, they remain higher than those in Caucasian women. Cervical cancer occurrence rates in Asian Americans and Pacific Islanders are about the same as those in Caucasians, and those in American Indian and Alaska Native women are lower. While the cancer occurrence rates are higher in Hispanics than in African Americans, the rate of death from cervical cancer is highest in African Americans. The rates of death are also higher in American Indians and Alaska Natives than in Hispanics. The lowest rates of death are seen in Caucasians, Asian Americans, and Pacific Islanders. Part of these differences is thought to be due to inequities in health care, although some genetic and cultural differences may also play a role. For example, those who do not smoke due to cultural or religious beliefs have a lower risk of cancer than those who do not share the same beliefs and do smoke. Familial tendencies Unlike breast cancer, where specific gene mutations that carry an increased risk of getting breast cancer have been identified, no gene mutations have been found that increase the risk of cervical cancer. Even so, a woman whose mother or sister had cervical cancer may have a risk of getting cervical cancer that is 2 to 3 times that of normal. It has been proposed that this familial tendency may be due to an inherited condition that limits some women's ability to defend against HPV infections.  This content is reviewed regularly. Last Updated 1/4/2010
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