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Cervical Cancer

By

Pedro T. Ramirez

, MD, The University of Texas MD Anderson Cancer Center;


Gloria Salvo

, MD, MD Anderson Cancer Center

Last full review/revision Feb 2019| Content last modified Feb 2019
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Cervical cancer develops in the cervix (the lower part of the uterus).

  • Cervical cancer usually results from infection with the human papillomavirus (HPV), transmitted during sexual intercourse.

  • Cervical cancer may cause irregular vaginal bleeding or bleeding after sexual intercourse, but symptoms may not occur until the cancer has enlarged or spread.

  • Papanicolaou (Pap) tests can usually detect abnormalities, which are then biopsied.

  • Getting regular Pap tests and being vaccinated against HPV can help prevent cervical cancer.

  • Treatment usually involves surgery to remove the cancer and often the surrounding tissue and often, if tumors are large, radiation therapy and chemotherapy.

In the United States, cervical cancer (cervical carcinoma) is the third most common gynecologic cancer among all women and is common among younger women. The average age at diagnosis is about 50, but it can affect women as young as 20.

The cervix is the lower part of the uterus. It extends into the vagina.

Locating the Internal Female Reproductive Organs

Locating the Internal Female Reproductive Organs

About 80 to 85% of cervical cancers are squamous cell carcinomas, which develop in the flat, skinlike cells that line the cervix. Most other cervical cancers are adenocarcinomas, which develop from gland cells.

Cervical cancer begins with slow, progressive changes in normal cells on the surface of the cervix. These changes, called dysplasia or cervical intraepithelial neoplasia (CIN), are considered precancerous. That means that if untreated, they may progress to cancer, sometimes after years. CIN is classified as mild (CIN 1), moderate (CIN 2), or severe (CIN 3).

Cervical cancer begins on the surface of the cervix and can penetrate deep beneath the surface. Cervical cancer can spread in the following ways:

  • By spreading directly to nearby tissues, including the vagina

  • By entering the rich network of lymphatic vessels inside the cervix, then spreading to other parts of the body

  • Rarely, by spreading through the bloodstream

Causes

Cervical cancer is most commonly caused by the human papillomavirus (HPV), which is transmitted during sexual intercourse. This virus also causes genital warts.

Risk factors for developing cervical cancer include the following:

  • Having sexual intercourse for the first time at a young age

  • Having more than one sex partner

  • Smoking cigarettes

  • Having a weakened immune system (due to a disorder such as cancer or AIDS or to drugs such as chemotherapy drugs or corticosteroids)

The younger a woman was the first time she had sexual intercourse and the more sex partners she has had, the higher her risk of cervical cancer.

Symptoms

Precancerous changes usually cause no symptoms. In the early stages, cervical cancer may cause no symptoms.

The first symptom of cervical cancer is usually abnormal bleeding from the vagina, most often after sexual intercourse. Spotting or heavier bleeding may occur between periods, or periods may be unusually heavy. Large cancers are more likely to bleed and may cause a foul-smelling discharge from the vagina and pain in the pelvic area.

If the cancer is widespread, it can cause lower back pain and swelling of the legs. The urinary tract may be blocked, and without treatment, kidney failure and death can result.

Diagnosis

  • Papanicolaou (Pap) tests

  • Biopsy

Routine Pap tests or other similar tests can detect the beginnings of cervical cancer. Pap tests accurately detect up to about 80% of cervical cancers, even before symptoms develop. Pap tests can also detect dysplasia. Women with dysplasia should be checked again in 3 to 4 months. Dysplasia can be treated, thus helping prevent cancer.

Biopsy

If a growth, a sore, or another abnormal area is seen on the cervix during a pelvic examination or if a Pap test detects dysplasia or cancer, a biopsy is done. Usually, doctors use an instrument with a binocular magnifying lens (colposcope), inserted through the vagina, to examine the cervix and to choose the best biopsy site.

Two different types of test are done:

  • Punch biopsy: A tiny piece of the cervix, selected using the colposcope, is removed.

  • Endocervical curettage: Tissue that cannot be viewed is scraped from inside the cervix.

These tests cause little pain and a small amount of bleeding. The two together usually provide enough tissue for pathologists to make a diagnosis.

If the diagnosis is not clear, a cone biopsy is done to remove a larger cone-shaped piece of tissue. Usually, a thin wire loop with an electrical current running through it is used. This procedure is called the loop electrosurgical excision procedure (LEEP). Alternatively, a laser (using a highly focused beam of light) can be used. Either procedure requires only a local anesthetic and can be done in the doctor’s office. A cold (nonelectric) knife is sometimes used, but this procedure requires an operating room and an anesthetic.

Staging of cervical cancer

If cervical cancer is diagnosed, its exact size and locations (its stage) are determined. Staging begins with a physical examination of the pelvis and a chest x-ray. Usually, computed tomography (CT), magnetic resonance imaging (MRI), or a combination of CT and positron emission tomography (PET) is done to determine whether the cancer has spread to nearby tissues or to distant parts of the body. If these procedures are not available, doctors may do other procedures to check specific organs, such as cystoscopy (bladder), sigmoidoscopy (colon), or IV urography (urinary tract).

Doctors usually also check for spread to the lymph nodes. Knowing whether cancer has spread to the lymph nodes and how many lymph nodes are involved helps doctors predict the person's outcome and plan treatment.

Stages of cervical cancer range from I (the earliest) to IV (advanced). Staging is based on how far the cancer has spread:

  • Stage I: The cancer is confined to the cervix.

  • Stage II: The cancer has spread outside the cervix, including the upper part of the vagina, but is still within the pelvis (which contains the internal reproductive organs, bladder, and rectum).

  • Stage III: The cancer has spread throughout the pelvis and/or the lower part of the vagina and/or blocks the ureters and/or causes a kidney to malfunction and/or spreads to the lymph nodes near the aorta (the largest artery in the body).

  • Stage IV: The cancer has spread outside the pelvis and/or to the bladder or rectum or to distant organs.

Prognosis

Prognosis depends on the stage of the cervical cancer. The percentages of women who are alive 5 years after diagnosis and treatment are

  • Stage I: 80 to 90% of women

  • Stage II: 60 to 75%

  • Stage III: 30 to 40%

  • Stage IV: 15% or fewer

If the cancer is going to recur, it usually does so within 2 years.

Did You Know...

  • Pap tests have reduced the number of deaths due to cervical cancer by more than 50%.

  • If all women had Pap tests regularly, deaths due to this cancer could be virtually eliminated.

  • Getting vaccinated against the human papillomavirus (HPV) helps prevent cervical cancer.

Prevention

Screening tests

Two types of tests are used to screen for cervical cancer:

  • Pap test: Cells from the cervix are examined under a microscope to determine whether any are cancerous or abnormal. Abnormal cells may, without treatment, progress to cancer (precancerous cells).

  • HPV test: A sample from the cervix is tested to determine whether HPV is present.

The number of deaths due to cervical cancer has been reduced by more than 50% since Pap tests were introduced.

How often these screening tests are done depends mainly on the woman’s age and results of previous tests. If women have no risk factors for cervical cancer and have had no abnormal test results in the past, testing may be done as follows:

  • From age 21 to 29: Usually every 3 years for the Pap test (HPV testing is not generally recommended)

  • Age 30 to 65: Every 3 years if only a Pap test is done or every 5 years if only an HPV test is done or if both tests are done (testing is done more often if women have risk factors for cervical cancer)

  • After age 65: No more testing if test results have been normal for the past 10 years

If women have not had abnormal Pap test results and have had their uterus removed for reasons other than cancer, they do not need to have Pap or HPV tests.

If all women had Pap tests as recommended, deaths due to this cancer could be virtually eliminated. However, in the United States, many women are not tested regularly. Also, many women who have cervical cancer have not had a Pap test in 10 years or more.

HPV vaccine

The HPV vaccine targets the types of HPV that cause most cervical cancers (and genital warts and other cancers, including those of the anus, vagina, penis, throat, and esophagus). The vaccine can help prevent cervical and other cancers but does not treat them.

Doctors recommend that girls and boys be vaccinated at age 11 or 12, but children can be vaccinated as early as age 9.

Being vaccinated before becoming sexually active is best, but even if girls or boys are already sexually active, they should be vaccinated.

For people under age 15, two doses of the vaccine are given 6 to 12 months apart.

For people over age 15, three doses of the vaccine are given. The first dose is followed by a dose 2 months later. The last dose is given 6 months after the first.

Condoms

Using condoms correctly during sexual intercourse can help prevent the spread of HPV. However, because condoms do not cover all the areas that can be infected, condoms do not fully protect against getting HPV.

Treatment

  • Surgery, radiation therapy, and/or chemotherapy, depending on the stage of the cancer

Treatment of cervical cancer depends on the stage of the cancer. It may include surgery, radiation therapy, and chemotherapy.

Precancerous changes and early stage I cervical cancer

Precancerous cervical cells (cervical intraepithelial neoplasia, or CIN) and cervical cancer that involves only the surface of the cervix (early stage I) are treated the same way. Doctors can often completely remove the cancer by removing part of the cervix using the loop electrosurgical excision procedure (LEEP), a laser, or a cold knife, done during a cone biopsy. These treatments preserve a woman’s ability to have children.

Because cancer can recur, doctors advise women to return for examinations and Pap tests every 3 months for the first year and every 6 months after that.

Rarely, removal of the uterus (hysterectomy) is necessary.

Late stage I and early stage II cervical cancer

If early-stage cancer involves more than the surface of the cervix but the cancer is still relatively small, treatment is typically

  • A hysterectomy plus removal of surrounding tissues (including the upper part of the vagina) and ligaments (radical hysterectomy) and nearby lymph nodes

Hysterectomy can be done by making a large incision in the abdomen (open surgery) or by using a thin viewing tube (laparoscope) and specialized surgical instruments inserted through small incisions just below the navel. Evidence suggests that when open surgery is done, the cancer is less likely to return and women are more likely to live longer.

If the cancer has grown or has begun to spread within the pelvis, treatment is typically one of the following:

  • Radiation therapy and chemotherapy (most common)

  • A radical hysterectomy with removal of nearby lymph nodes and sometimes with radiation therapy

Either treatment results in about 85 to 90% of women being cured. The ovaries are usually left in place because cervical cancer is unlikely to spread (metastasize) to the ovaries.

If doctors discover during surgery that cancer has spread outside the cervix, hysterectomy is not done, and radiation therapy plus chemotherapy is recommended.

Late stage II through early stage IV cervical cancer

When cervical cancer has spread further within the pelvis or has spread to other organs, the following treatment is preferred:

  • Radiation therapy plus chemotherapy such as cisplatin

Doctors may use a laparoscope or do surgery to determine whether lymph nodes are involved and thus determine where radiation should be directed. External radiation (directed at the pelvis from outside the body) is used to shrink the cancer and treat cancer that may have spread to nearby lymph nodes. Then radioactive implants are placed in the cervix to destroy the cancer (a type of internal radiation called brachytherapy).

Chemotherapy is usually given with radiation therapy, often to make the tumor more likely to be damaged by radiation therapy.

If the cancer remains in the pelvis after radiation therapy, doctors may recommend surgery to remove some or all pelvic organs (called pelvic exenteration). These organs include the reproductive organs (vagina, uterus, fallopian tubes, and ovaries), bladder, urethra, rectum, and anus. Which organs are removed and whether all are removed depends on many factors, such as the cancer's location, the woman's anatomy, and her goals after surgery. Permanent openings—for urine (urostomy) and for stool (colostomy)—are made in the abdomen so that these waste products can leave the body and be collected in bags. After the procedure, women usually have some bleeding, a discharge, and considerable tenderness and pain for a few days. Typically, the hospital stay is 3 to 5 days. Complications, such as infection or opening of the surgical incision, blockages in the intestine, and formation of abnormal connections between organs (fistulas), can occur. This procedure cures up to 40% of women.

Extensive spread or recurrence of cervical cancer

The main treatment for extensive spread or recurrence of cervical cancer is

  • Chemotherapy, usually with paclitaxel plus cisplatin or topotecan

However, chemotherapy reduces the cancer’s size and controls its spread in only 15 to 25% of women treated, and this effect is usually only temporary. Adding another drug (bevacizumab—a monoclonal antibody used to treat several types of cancer) may extend survival by a few months.

Sentinel lymph node dissection

A sentinel lymph node is the first lymph node that cancer cells are likely to spread to. There may be more than one sentinel lymph node. These nodes are called sentinel lymph nodes because they are the first to warn that cancer has spread.

A sentinel lymph node dissection involves

  • Identifying the sentinel lymph node (called mapping)

  • Removing it

  • Examining it to determine whether cancer cells are present

To identify sentinel lymph nodes, doctors inject a blue or green dye and/or a radioactive substance into the cervix near the tumor. These substances map the pathway from the cervix to the first lymph node (or nodes) in the pelvis. During surgery, doctors then check for lymph nodes that look blue or green or that give off a radioactive signal (detected by a handheld device). Doctors remove this node (or nodes) and send it to a laboratory to be checked for cancer. If the sentinel lymph node or nodes do not contain cancer cells, no other lymph nodes are removed (unless they look abnormal).

Sentinel lymph node dissection may help doctors limit the number of lymph nodes that need to be removed, sometimes to only one. Removing lymph nodes often causes problems such as accumulation of fluids in tissues, which can cause persistent swelling (lymphedema), and nerve damage.

Pregnancy and cervical cancer

Treatment with radical hysterectomy, chemotherapy, and/or radiation therapy usually makes it impossible for women to become pregnant or to carry a pregnancy to term. However, advances in assisted reproductive techniques may enable women to have a child after these procedures. If being able to have children is important to them, women should talk to their doctor and get as much information as possible about risks of and requirements for these procedures, as well as the likelihood of becoming pregnant and having a child after such a procedure.

If women with early-stage cervical cancer wish to preserve their ability to have children, a different cancer treatment called radical trachelectomy (a fertility-preserving treatment) may be done. Doctors remove the cervix, the tissue next to the cervix, the upper part of the vagina, and the lymph nodes in the pelvis. To remove these tissues, doctors may do one of the following:

  • Do open surgery

  • Use a laparoscope inserted through a small incision just below the navel, then thread instruments through the laparoscope, sometimes with robotic assistance (laparoscopic surgery)

  • Remove the tissues through the vagina (vaginal surgery)

Then the uterus is re-attached to the lower part of vagina. Thus, women still can become pregnant. However, babies must be delivered by cesarean. About 50 to 70% of women who have this procedure become pregnant.

Trachelectomy appears to be as effective as radical hysterectomy for many women with early-stage cervical cancer. The cancer recurs in about 5 to 10% of women.

Complications of radiation therapy

Radiation therapy may irritate the bladder or rectum. Later, as a result, the intestine may become blocked, and the bladder and rectum may be damaged. Also, the ovaries usually stop functioning, and the vagina may narrow.

More Information

Drugs Mentioned In This Article

Generic Name Select Brand Names
AVASTIN
TAXOL
PLATINOL
HYCAMTIN
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