Cervical Cancer

Cervical cancer is caused by the human papillomavirus (HPV).

Cervical cancer is cancer that begins in the uterine cervix, the lower end of the uterus that contacts the upper vagina. Cervical cancer occurs in almost 14,000 women each year in the U.S., leading to about 4,300 deaths. Since 1980, the incidence of cervical cancer has fallen by 45%, and the mortality (death) rate for cervical cancer has declined by 49%. Survival rates among African-American women are lower than for any other racial or ethnic group in the U.S. Cervical cancer remains a common cause of cancer and cancer death in women in developing countries without access to screening (Pap testing) for cervical cancer or vaccines against human papillomaviruses (HPVs).

Cervical cancer is different from cancer that begins in other regions of the uterus (uterine or endometrial cancer). If detected early, cervical cancer has a very high cure rate. Vaccination against HPVs, which are known to cause cervical cancer, is an effective preventive measure.

Cervical cancer may not produce any symptoms or signs. In particular, early-stage cervical cancers, like precancerous changes, typically do not produce symptoms. Symptoms may develop when the cervical cancer cells start to invade surrounding tissues.

Symptoms and signs of cervical cancer include:

• Abnormal vaginal bleeding
• Vaginal bleeding after menopause
• Vaginal bleeding after sex
• Bleeding or spotting between periods
• Longer or heavier menstrual periods than usual
• Other abnormal vaginal discharge
• Pain during sexual intercourse

It is important to note that these symptoms are not specific to cervical cancer and can be caused by a variety of conditions.

Most cervical cancers are caused by longstanding infection with one of the human papillomaviruses (HPVs). HPV infection is very common, and most people with HPV infection do not develop cancer. There are over 100 types of HPVs, and only certain types have been linked to cancers. Other HPV types cause benign warts on the skin or genitals. The so-called "high risk" HPV types have been shown to cause cancers of the cervix as well as cancers of the penis in men.

HPVs also can cause cancers of the:

• Mouth
• Throat
• Anus in people of both sexes

HPV infection is spread through sexual contact or skin-to-skin contact. Many studies have shown that HPV infection is common and that a majority of people will be infected with HPV at some point in life.

Human papilloma viral infections typically resolve on their own. In some women, the HPV infection persists and causes precancerous changes in the cells of the cervix. These changes can be detected by regular cervical cancer screening (known as Pap testing).

In Pap testing, a superficial sample of cells from the cervix is taken with a brush or swab during a routine pelvic examination and sent to a laboratory for analysis of the cells' appearance.

Is cervical cancer inherited (genetic)?

There is no known genetic cause of cervical cancer. However, it may run in some families. Women with a mother or sister who had the disease have a higher risk of developing it themselves. It is currently not understood if this familial tendency is caused by an inherited condition that makes some women more vulnerable to HPV infection than others. Alternatively, the increased incidence in some families may be related to the likelihood that family members may share one or more of the other non-genetic risk factors described previously.

There is no known genetic cause of cervical cancer. However, it may run in some families. Women with a mother or sister who had the disease have a higher risk of developing it themselves. It is currently not understood if this familial tendency is caused by an inherited condition that makes some women more vulnerable to HPV infection than others. Alternatively, the increased incidence in some families may be related to the likelihood that family members may share one or more of the other non-genetic risk factors described previously.

As described previously, cervical cancers are caused by infection with one of the high-risk HPV types. However, since not all people who are infected with HPV will develop cancer, it is likely that other factors also play a role in the development of cervical cancer.

Certain risk factors have been identified that increase a woman's risk of developing cervical cancer:

• Tobacco smoking
• HIV infection
• Immune system suppression
• Past or current Chlamydia infection
• Overweight
• Long-term use of oral contraceptives (although the risk returns to normal when the contraceptive pills are discontinued)
• Having three or more full-term pregnancies
• Having a first full-term pregnancy before age 17
• Poverty
• Family history of cervical cancer

Dysplasia is abnormal-appearing cells that are not cancers but may be precancerous. Dysplasia of the cervix identified at the time of Pap testing is referred to as a squamous intraepithelial lesion (SIL).

Cervical intraepithelial neoplasia (CIN) is another term used to classify precancerous changes in the cervix that are seen on tissue samples such as biopsies. Precancerous changes in the cervix such as CIN and SIL can typically be treated, which can prevent the development of cancer.

The cervix itself contains two types of cells that line the outer cervix, known as squamous cells and the cells that line the interior channel of the cervix. These interior cells have features of glandular cells. The point at which the squamous and glandular cells meet is known as the transition zone, and it is in this area that most cervical precancers and cancers begin to grow. Up to 90% of cervical cancers arise from the squamous cells and are called squamous cell carcinomas, with most of the remaining tumors coming from the glandular cells (adenocarcinomas).

The stage of any cancer refers to the extent to which it has spread in the body at the time of diagnosis. Staging cancers is an important part of determining the best treatment plan. Both the FIGO (International Federation of Gynecology and Obstetrics) system and the AJCC (American Joint Committee on Cancer) have developed systems to stage cervical cancer. Both systems are based on the tumor extent, spread to any lymph nodes, and distant spread. The stage is classified as a range from 0 to IV, with many subcategories within each numerical stage.

In general, the five stages of cervical cancer are:

1. Stage 0: This stage is not a true invasive cancer. The abnormal cells are only on the surface of the cervix, as in CIN 3. This stage is not included in the FIGO system and is referred to as carcinoma in situ (CIS).
2. Stage I: There is a small amount of tumor present that has not spread to any lymph nodes, organs, or distant areas of the body.
3. Stage II: The tumor has spread beyond the cervix and uterus, but does not invade the pelvic walls or the lower part of the vagina.
4. Stage III: Cancer has grown into the lower part of the vagina or the walls of the pelvis. The tumor may be blocking the ureters (tubes that carry urine from the kidneys to the bladder). There is no spread to other sites in the body.
5. Stage IV: This is the most advanced stage, in which cancer has spread to the bladder or rectum, or sites in other areas of the body.

The American Cancer Society (ACS) recommends that women aged 25 to 65 have a primary HPV test every 5 years. If primary HPV testing is not available, screening may be done with either a co-test that combines an HPV test with a Papanicolaou (Pap) test every 5 years or a Pap test alone every 3 years. 

Those over age 65 who have had regular screening in the past 10 years with normal results and no history of CIN2 or a more serious diagnosis within the past 25 years should stop cervical cancer screening. Once stopped, cervical cancer screening should not be started again.

Women who have had a total hysterectomy for a benign condition no longer have a cervix, and thus do not need to be screened for cervical cancer. However, women who have had a subtotal hysterectomy still have a cervix and should be screened.

Certain conditions and special situations may change the frequency of screening, such as a history of abnormal Pap smears.

As mentioned previously, HPV and Pap testing are typical screening procedures. If abnormal cells are detected on a Pap smear, a colposcopy procedure is then performed. A colposcopy uses a lighted microscope to examine the external surface of the cervix during a pelvic examination. If abnormal areas are noted, a small tissue sample (biopsy) is taken for examination by a pathologist to look for precancerous changes or cancer. Colposcopy requires no special anesthesia and is similar to having a Pap smear in terms of discomfort.

The transformation zone of the cervix (see above) cannot always be visualized well during colposcopy. In this case, a sample of cells may be taken from the interior canal of the cervix, known as an endocervical curettage or scraping. Another option is conization or removal of a cone-shaped portion of the cervix around the cervical canal. This tissue can be removed with a thin loop of wire heated by an electrical current and is called loop electrosurgical excision procedure (LEEP) and is a large loop excision of the transformation zone (LLETZ). LEEP is performed in the doctor's office with a local anesthetic. Another possibility is to have the cone-shaped tissue fragment removed in an operating room under general or regional anesthesia, referred to as cold knife conization.

After a conization or biopsy procedure, the pathologist studies the tissue to determine if precancerous changes (referred to as cervical intraepithelial neoplasia grades 1 to 3, depending on its extent) or cancer are present.

If cancer is present, depending on the size and extent of the tumor, other tests might be done to help determine the extent to which the tumor has spread. These additional tests can include chest X-rays, or CT or MRI imaging studies. Cystoscopy (examination of the interior of the urinary bladder using a thin, lighted scope) or proctoscopy (examination of the rectum) may be necessary. An examination under anesthesia allows the doctor to perform a manual pelvic examination without causing pain to help determine the degree of spread of cancer within the pelvis.

The treatment for cervical cancer depends upon many factors, including the stage of cancer when it is diagnosed. Surgery, radiation therapy, chemotherapy, and targeted therapy are common methods of treatment for cervical cancer.

• Surgery is often performed to remove cancer, especially in early-stage tumors. Hysterectomy (removal of the uterus) may be performed, but other procedures that preserve the ability to carry a pregnancy can be done in younger women with small tumors. Both a cone biopsy (removal of the inside of the cervix where most tumors begin) and a trachelectomy (removal of the upper vagina and cervix) are options that can be used for small tumors to preserve fertility. For more advanced cancers, a procedure known as pelvic exenteration removes the uterus, surrounding lymph nodes, and parts of other organs surrounding the cancer, depending on its location.
• Radiation therapy is another common treatment. Both external beam radiation therapy (radiation therapy administered from an outside source of radiation) and brachytherapy (radiation therapy that involves the insertion of radioactive sources near the tumor for a fixed period) have been used for cervical cancer. These two types of therapy have also been used together. If radiation therapy is given as the main treatment for cancer, it is often combined with chemotherapy. Side effects of radiation therapy include fatigue, diarrhea, skin changes, nausea, vomiting, irritation of the bladder, vaginal irritation and discharge, and sometimes menstrual changes or early menopause if the ovaries are exposed to radiation.
• Chemotherapy may be recommended together with radiation therapy (chemoradiation) for some stages of cervical cancer. It may also be given before or after radiation treatment. Chemotherapy drugs commonly used for cervical cancer include cisplatin and 5-fluorouracil. Chemotherapy may also be the treatment of choice for cervical cancer that has come back after treatment. Side effects of chemotherapy include nausea, fatigue, vomiting, hair loss, and mouth sores.
• Targeted therapy refers to drugs that have been specifically developed, or targeted, to interrupt cellular processes that promote the growth of cancer cells. Bevacizumab (Avastin) is an example of targeted therapy. Target therapy inhibits the ability of tumors to make new blood vessels, which is required for tumor growth. This kind of targeted therapy is sometimes used for advanced cervical cancers.

As with most cancers, the prognosis is better for cancers that are detected in early stages than for advanced cancers. The outlook for cancer often is reported in five-year survival rates. Currently, survival rates for cervical cancer are based on patients who were diagnosed years ago, so these rates may be different in people diagnosed today and receiving modern treatments.

It is important to note that many people with cancer live far beyond five years, and these rates include death from any cause, not just the cancer being studied.
The five-year survival rates by stage for cervical cancer are:

• Stage I: 80%-93%
• Stage II: 58%-63%
• Stage III: 32%-35%
• Stage IV: 15%-16%

Survival rates are based on examinations of large groups of people and do not reflect the outcome or expected course for any one individual patient. Many other factors, including overall health status and the response of cancer to treatment, can affect the prognosis of a specific patient.

Yes, cervical cancer often can be prevented with vaccination and modern screening techniques that detect precancerous changes in the cervix. The incidence of cervical cancers in the developed world declined significantly after the introduction of Pap screening to detect precancerous changes, which can be treated before they progress to become cancer.

Moreover, vaccines are available against the common types of HPV that cause cervical cancer. The vaccine is typically given at age 11-12 and required two doses, 6-12 months apart.

Vaccination should occur before sexual activity to offer the full benefit of the vaccine. The CDC recommends that 11- to 12-year-olds receive the HPV vaccine, and those under 26 should get the vaccine if they did not receive any or all doses when they were younger.

• Research is ongoing, not only to improve methods to treat cervical cancer but also to improve methods of treating precancers and detecting cancers in early, treatable stages.
• Drug treatments, including the application of antiviral medications to the cervix, are being studied as an alternative or complement to surgical management of precancerous changes in the cervix.
• For existing cancers, new-targeted therapies always are being studied. Testing of HPV vaccines continues to determine whether vaccines may be able to help a woman's immune system fight off an existing HPV infection.
• Clinical trials are an option for many cancer patients. Clinical trials are research studies that involve actual patients, looking at new treatments or a combination of treatments for a condition. Your doctor can help you decide if a clinical trial might be right for you.
• A listing of clinical trials that are available for all types of conditions around the world can be found at ClinicalTrials.gov.

As with any cancer diagnosis, emotional support from family, friends, clergy, a counselor, or a support group can help you and your family learn about the illness and cope with the diagnosis and effects of treatment. Every woman is different, and different women will be comfortable with different kinds of support systems. For those who prefer a more organized form of support, patient and family support groups are offered by cancer treatment centers, hospitals and clinics, and national advocacy organizations. Your place of worship may also provide cancer support groups. There are even online support groups for those who prefer this option.

The following is only a partial listing of sources for emotional and coping support for those with cervical cancer:

• The American Cancer Society (ACS) Cancer Survivors Network
• I Can Cope (online) is an ACS-sponsored online course on coping with cancer
• The National Cancer Information Center provides information and support to those facing cancer 24 hours a day, 365 days a year. Trained cancer information specialists are available via phone (1-800-227-2345), email, or live chat.
• The National Cervical Cancer Coalition offers online support groups and coping resources.
• ACS guide on sexuality for women with cervical cancer, during and after treatment