Cervical cancer

Cervical cancer develops when the cells of the cervix grow out of control. Unlike normal cells, which divide and grow in an organized fashion, malignant cancer cells continue to divide until they form a growth or tumor (a mass of excess tissue). In some cases, the cancer cells become invasive, spreading to tissues and organs outside of the cervix (metastasis).

The cervix is the bottom part of the uterus (womb). During pregnancy, the fetus grows in the top part (body) of the uterus. The cervix connects the uterine body to the vagina (birth canal). The part of the cervix that is closest to the uterine body is known as the endocervix. The part of the cervix that is next to the vagina is called the ectocervix. The majority of cervical cancers begin where the endocervix and ectocervix meet.

Most cervical cancers develop slowly, in the lining of the cervix. Healthy cervical cells develop abnormal precancerous changes over time known as cervical dysplasia. These cells can potentially develop into cancer. Precancerous cells often do not become malignant (cancerous), and may disappear without treatment. Abnormal cells that remain can be treated to prevent cervical cancer. If the cancer is not treated in this earliest stage in the lining of the cervix, it can invade other cervical tissue and is considered invasive cervical cancer.

An estimated 11,00 cases of invasive cancer of the cervix were estimated to be diagnosed in the United States in 2007, according to the American Cancer Society (ACS). Cervical cancer has a higher incidence among certain populations, including Vietnamese American, black and Hispanic women, according to the U.S. Centers for Disease Control and Prevention (CDC). In addition, women with fewer opportunities for regular gynecological examinations and screening also have a higher risk for the disease. According to some researchers, noninvasive cervical cancer (carcinoma in situ) is approximately four times as prevalent as its invasive counterpart.

Cancer of the cervix tends to occur during midlife, with half of patients diagnosed between 35 and 55 years of age. Cervical cancer rarely affects women under the age of 20 years. Because more than 20 percent of women are diagnosed with cervical cancer after they reach age 65, it is important for women to have annual Pap tests until age 70, and sometimes longer. Cervical cancer affects a small number of pregnant women. If the cancer is in an early stage, most physicians believe that expectant mothers can safely carry their baby to term.

Cervical cancer was once among the leading causes of death of American women. However incidences of invasive cervical cancer have declined steadily over the years in developed countries. In the United States, only about 3,700 women are expected to die from invasive cervical cancer during 2007.

The U.S. death rate from this condition continues to decrease by nearly 4 percent a year. Between 1998 and 2002, the overall rates of women in the United States diagnosed with invasive cervical cancer declined 17 percent, according to the ACS. This decline is primarily attributed to increased use of the Pap smear, a screening procedure that detects cervical changes before cancer develops. However, higher rates continue to exist among the Hispanic and black women.

Healthcare professionals hope that widespread use of the FDA-approved human papillomavirus (HPV) vaccine will contribute to a continuing decline in the incidence of cervical cancer. Research has shown that this vaccine is effective against the types of HPV associated with 70 percent of cervical cancers.

The five-year survival rate of this disease is about 72 percent. When detected at its earliest stage, invasive cervical cancer has a much higher survival rate of 92 percent.

Women with cervical precancer or early cervical cancer usually have no signs or symptoms of the disease. Symptoms of cervical cancer typically appear when the cancer becomes invasive and spreads (metastasizes) to nearby tissue. When this occurs, the most common symptom is irregular vaginal bleeding.

Cervical cancer also may produce an unusual vaginal discharge that is separate from the patient's normal monthly menstrual period. Such discharges can be pale or watery and may include light bleeding or blood spots. Discharges may occur between menstrual periods. Additionally, menstrual bleeding may be heavier or last longer than normal. Increased vaginal discharge or bleeding after menopause and pain during sexual intercourse may be symptoms of cervical cancer as well.

It is important to note that these signs and symptoms may be caused by conditions other than cervical cancer. Patients experiencing any of these symptoms should immediately notify their physician.

The two main types of cervical cancer are classified by the cells’ appearance under a microscope.

On occasion, cervical cancers possess features of both adenocarcinomas and squamous cell carcinomas. These rare cancers are called adenosquamous or mixed carcinomas.

Although all of the exact causes of cervical cancer are not known, there are certain risk factors that may increase a woman’s likelihood of developing this disease.

The most significant risk factor for cancer of the cervix is infection with human papillomavirus (HPV). HPVs are a collection of more than 100 types of viruses that can cause noncancerous tumors (masses of excess tissue) called papillomas (warts). HPV infection is common among women and men throughout the world.

Data from The National Health and Nutrition Examination Survey (NHANES) published in February 2007 provided the first national estimate of the prevalence of HPV infection among women in the United States. Researchers found that nearly 27 percent of women between the ages of 14 and 59 tested positive for one or more strains of HPV. The prevalence was highest in women 20 to 24 years of age.

Different types of HPV affect different regions of the body. For example, warts that appear around the male and female genitals are a form of HPV commonly known as genital warts. This infection is transmitted during skin-to-skin sexual contact, including vaginal and anal intercourse and oral sex. Genital warts do not typically lead to cervical cancer, and therefore, this type of HPV is labeled low risk.

However, other high-risk forms of HPV can cause cervical cancer. Two strains in particular (HPV-16 and HPV-18) account for about two-thirds of cervical cancers, according to the American Cancer Society (ACS). Other "high risk" strains of HPV include HPV 31, HPV 33 and HPV 45. In most cases, the infection produces no symptoms and clears spontaneously because of the immune system’s response to the virus. Not all of the women infected by HPV will develop cervical cancer, but HPV-16 and HPV-18 infection place women at greater risk for developing cervical cancer.

These viruses are also a major cause of penile cancer, a rare cancer that occurs in men. Health officials emphasize that use of condoms prevent transmission of HPV only in the areas of the penis covered by the condom. Condom use does not prevent transmission of the virus in the uncovered areas. In 2006, the U.S. Food and Drug Administration (FDA) approved an HPV vaccine, which protects women against four strains of the virus, including HPV-16 and HPV-18. The vaccine is most effective on women who have not been previously exposed to HPV.

These include:

Regular gynecological examinations can help prevent precancerous cells from developing into invasive cervical cancer. The diagnosis of cervical cancer begins with a pelvic examination, which will include a Pap smear. The Pap smear is the most commonly used screening test to detect cervical changes before cancer develops. Pap smears are usually conducted by a woman’s obstetrician-gynecologist as part of a regular gynecological examination. However, Pap smears may be conducted by other physicians, such as a family practitioner.

During a Pap smear, the patient lies on a table while the physician inserts an instrument called a speculum into her vagina. The speculum holds the vagina open while the physician cleans the patient’s cervix with a cotton swab and collects a sample of cells from the cervix using a tiny spatula, small brush or a cotton swab. The cell sample is then placed on a glass slide and sent to a laboratory for analysis.

If the Pap smear indicates the presence of irregularly shaped cells, known as dysplasia, or cancerous cells, the physician will need to conduct further testing. For example, another test used in cervical cancer screening is a test for the DNA of the human papillomavirus (HPV). The test uses a test sample similar to the Pap smear to identify some of the most common and high risk types of HPV. If HPV is identified, further DNA testing can indicate which strains are present. The HPV DNA test may be used as a next step after irregular Pap smear results. It may also be offered to women over age 30 as a screening test along with the Pap smear. The HPV DNA test is not routinely used in screening for younger women because HPV is more common in that age group and rarely causes cancer at that point.

Other diagnostic tests can include:

When cervical cancer is diagnosed, the physician will recommend one or more options for treatment. Patients diagnosed with cervical cancer will be treated by a cancer care team, which usually includes a gynecologist with oncology training (gynecologic oncologist), a medical oncologist and other healthcare professionals.

Treatment is based on many factors, including the patient’s age, health status, interest in future childbearing, as well as the stage of the cancer. Depending on the cancer’s stage, treatment goals may include recovery, preventing tumors from growing, spreading or recurring (coming back after treatment), and symptom relief. Patients may choose to get a second opinion about their condition prior to beginning treatment. The basic types of treatment for cervical cancer include surgery, radiation therapy and chemotherapy. Patients with cervical cancer may be treated with one of the forms of therapy but in most cases, they receive a combination of these treatments.

Surgical procedures for treating cervical cancer include:

Physicians will often destroy cervical cancer cells with high-energy radiation. This radiation may be administered from a machine externally, using a type of therapy called external beam radiation therapy, which is similar to a diagnostic x-ray. A second type of radiation therapy called brachytherapy is usually completed in a few days. During brachytherapy, radioactive material is inserted into the vagina near the tumor or placed inside thin needles that are injected into the tumor. This form of therapy may reduce a woman’s ability to become pregnant in the future.

Chemotherapy uses powerful drugs to destroy cancer cells. These drugs are typically administered either intravenously or orally over a period of time. After the drugs enter the patient’s bloodstream, they begin to spread throughout the body. This makes chemotherapy potentially useful in treating cancer that has spread to other organs in the body. In certain cases, combination chemotherapy may be more effective in treating cancer than a single drug alone. Chemotherapy may lead to infertility in some patients.

Patients may choose to participate in clinical trials or studies involving promising new or experimental treatment methods for cervical cancers. Patients should discuss clinical trials with their physician before agreeing to become a participant.

Each type of cervical cancer treatment may have side effects. These may affect the cervix and other reproductive organs and involve fertility and sexual function. Other pelvic organs such as the bladder and colon may also be impacted. Patients who receive cervical cancer treatments should consult their physician regarding potential side effects and report any new symptoms or side effects as soon as they arise.

Many cervical precancers (cells that have the potential to become cancerous) can be prevented by avoiding exposure to the human papillomavirus (HPV). Women can minimize their exposure to HPV in their sexual life by:

• Refraining from sex at an early age.
• Limiting the number of sexual partners.
• Limiting male sexual partners who have many other sexual partners.

Using condoms consistently. Condoms can protect against some HPV transmission if they are used consistently, but HPV can still be transmitted on areas of skin or tissue not covered by condoms. In 2006, Gardasil, the first HPV vaccine was approved by the U.S. Food and Drug Administration. The vaccine protects against four strains of HPV: HPV-16 and HPV-18, which cause 70 percent of cervical cancer cases, and HPV-6 and HPV-11, which cause 90 percent of genital warts. The vaccine is administered in three doses over a six-month period.

Recently published studies have shown that Gardasil provides highly effective protection against cervical, vaginal and vulvar diseases caused by the four HPV strains. The studies also found that the vaccine is effective in protecting women against advanced cervical pre-cancers caused by HPV-16 and HPV-18. The vaccine can only be used to prevent HPV infection and cannot be used to treat an existing infection (i.e., after an abnormal Pap test).

The American Cancer Society (ACS) issued the following recommendations regarding the HPV vaccine to prevent cervical cancer and precancerous conditions:

• Routine HPV vaccine for females aged 11 to 12 years.
• Vaccine may be given to girls as young as age 9.
• Vaccine should be given to females aged 13 to 18 years old to catch up missed vaccine or complete the vaccination series.
• Vaccination for women aged 19 to 26 should be decided on an individual basis. Women should discuss the benefits of the vaccine with their healthcare professional. Ideally, the vaccine should be given before the female is sexually active.
• Vaccine is not currently recommended for women over the age of 26 or for males.
• Screening for cervical changes should continue in both vaccinated and unvaccinated women.

Certain factors can affect the accuracy of the Pap test.

The Bethesda System (TBS) is the most widely used method of describing the results of Pap tests.

The prognosis (predicted outlook or chance of survival) of cervical cancer depends on the cancer’s stage. The stage indicates the extent of the cancer, or how widespread the disease is in the body. The staging system for cervical cancer is called the FIGO (International Federation of Gynecology and Obstetrics) system. The FIGO system for staging cervical cancer is a clinical staging system, which means that staging is based on the patient’s physical examination and test results. The FIGO system categorizes the cancer in stages 0 through IV, and divides some of the stages even further (e.g., stages I, IA, IA1 and IA2):

• Stage 0: Carcinoma in situ. The tumor is very superficial, affecting only the cells that line the cervix with no evidence of invasion.
• Stage I: The cancer is contained in the cervix and has not spread into the connective tissue outside the cervix, and may or may not be visible to the naked eye.
• Stage II: The cancer has spread from the cervix into neighboring areas, such as the parametrial tissue (tissue located next to the cervix), but is still inside the pelvic region.
• Stage III: The cancer has spread from the cervix into the lower region of the vagina or the pelvic wall. It may be blocking the tubes that transport urine from the kidneys to the bladder (ureters).
• Stage IV: The most advanced stage of cancer of the cervix. The cancer has invaded nearby organs and other body parts, such as the bladder, rectum or spread to the lungs.