Cervical cancer

Squamous Intraepithelial Lesions

What is 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.

Signs and symptoms of cervical cancer

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.

Types and differences of cervical cancer

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

They include:

  • Squamous cell carcinoma. According to the American Cancer Society (ACS), approximately 80 to 90 percent of cervical cancers are squamous cell carcinomas. The cells that compose these cancers resemble the thin, flat squamous cells that line the surface of the endocervix (the part of the cervix that is closest to the uterine body). Squamous cell carcinomas typically begin where the endocervix and ectocervix (the part of the cervix that is next to the vagina) converge.
  • Adenocarcinoma. These cancers account for the remaining 10 to 20 percent of cervical cancers, according to the ACS. Adenocarcinomas, which develop from the gland cells that produce mucous in the endocervix, are becoming more common in patients born in the last 20 to 30 years.

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

Risk factors and causes of cervical cancer

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.

Women can reduce their risk of becoming infected with HPV by:

  • Getting vaccinated against HPV if their physician indicates they are a good candidate for the vaccine
  • Refraining from sexual activity at an early age
  • Limiting their number of sexual partners
  • Avoiding sex with men who have had multiple partners
  • Using condoms consistently every time they have sex
  • Other conditions are also risk factors for cervical cancer.

These include:

Human immunodeficiency virus (HIV) infection

HIV is the virus that causes AIDS (acquired immune deficiency syndrome). Women with HIV have compromised immune systems and therefore are more likely to contract HPV, which may lead to cervical cancer. Scientists believe that a patient’s immune system plays a vital role in eliminating and slowing the progression of cancer cells. Therefore, cervical cancer in patients with HIV may become invasive more quickly than in patients with healthy immune function.

Chlamydia infection

Chlamydia is one of the most common sexually transmitted diseases in the United States. This bacterial infection is spread through sexual contact, and many women do not realize that they have become infected because they experience no symptoms. Recent studies of blood tests suggest that women with past or current chlamydia infection are at greater risk of developing cervical cancer than women who have never had chlamydia. Further studies are needed to support this finding.

Diethylstilbestrol (DES)

DES is a hormonal drug that was prescribed from 1940 to 1971 to reduce the risk of miscarriages in some women. One daughter of every 1,000 mothers who took DES during pregnancy develops cancer of the vagina or cervix. The incidence of these cases of cervical cancer appears to be falling. Most DES-exposed women who developed cervical cancer developed it at a young age and the youngest women exposed to this drug in utero are now in their late 30s.

Additional risk factors of cervical cancer include:

  • Smoking
  • Excess body weight
  • Diet low in fruits and vegetables
  • Family history of cervical cancer
  • Having multiple full-term pregnancies
  • Low socioeconomic status (which is often accompanied by poor access to healthcare and fewer screenings for the disease)

Diagnosis methods for cervical cancer

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:


A test conducted by a gynecologist using a colposcope to further examine the cervical cells. The colposcope is an instrument with a magnifying lens that allows the physician to view the surface of the cervix with magnifying lenses.

Colposcopic biopsy

During a colposcopy, the physician uses biopsy forceps to obtain a sample of cervical tissue for examination under a microscope.

Endocervical curettage (endocervical scraping)

Part of the tissue that lines the endocervical canal (the passage between the inner and outer part of the uterus) is removed by scraping using a narrow instrument called a curette, which scrapes the tissue. This procedure typically accompanies a colposcopy, and the tissue sample is sent to the laboratory for analysis.

Cystoscopy and proctoscopy

During a cystoscopy, the physician checks the bladder and urethra using a thin tube with a light and a lens. If the patient has cervical cancer, the physician uses this procedure to help determine if the disease has spread into these areas. Additionally, the physician can remove small tissue samples for pathologic (microscopic) testing during this procedure. A cytoscopy and proctoscopy can be done with local or general anesthesia.

During a proctoscopy, the physician views the rectum through a lighted tube to determine if cervical cancer has spread into this region. The physician will also do a thorough pelvic examination by viewing and feeling the patient’s reproductive organs while she is under anesthesia. This helps to determine whether the cancer has spread outside of the cervix.

Imaging tests

If the physician determines that the patient has cervical cancer, certain imaging studies may be performed. These include:

  • CAT scan. During computerized axial tomography, the patient lies on a table while an x-ray scanner rotates around the body, capturing cross-sectional images. It may be performed with contrast material (dye) to help outline tissues and organs.
  • MRI. Magnetic resonance imaging uses strong magnets and radio waves to produce cross-sectional images of the body, much like a CAT scan. In addition, MRIs can also produce images that are parallel with the length of the body, which can be useful in identifying the spread of cancer to the spinal cord and brain. MRIs are particularly helpful in examining pelvic tumors.
  • PET scan. In positron emission tomography, a scanning machine takes images after the patient is injected with glucose (sugar) containing a radioactive atom. PET scans are useful for detecting whether cancer has invaded the lymph nodes and how far it has spread to other areas of the body.
  • Intravenous urography. Also called an intravenous pyelogram or IVP, this x-ray procedure helps detect urinary tract abnormalities that may be caused by cervical cancer. Before this procedure, a special dye is injected into the patient’s vein. The kidneys remove the dye from the bloodstream and pass it into the bladder. Patients who have already had an MRI or CAT scan may not require this test.

Treatment options for cervical cancer

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:

Cryotherapy (also called cryosurgery)

The abnormal cells are destroyed with a metal probe that is dipped in liquid nitrogen. This procedure, also known as ablation, is used to treat precancer (cells that have the potential to become cancerous) and early stages of cancer. Cryotherapy does not interfere with a woman’s ability to become pregnant at a later date.

Laser therapy (also called laser surgery)

The abnormal cells are vaporized by a focused laser beam. This procedure may be used to remove a tissue sample for study. Laser surgery is used to treat precancer and early stages of cancer. This therapy is not used in the treatment of invasive cancer, and does not affect a woman’s ability to become pregnant in the future.

Conization (cone biopsy)

This procedure uses a surgical or laser knife (cold knife cone biopsy) or a thin, heated wire (LEEP or LEETZ procedure) to remove a cone-shaped tissue sample from the cervix. Cone biopsy is rarely used as the sole form of treatment, except in cases of precancer or early cancer where the patient may still want to have children. Cone biopsy may also be used to establish the cancer diagnosis prior to surgery or radiation treatment.

Simple hysterectomy

A surgical procedure to remove the cervix and the body of the uterus. This surgery requires general or regional anesthesia, and typically requires a three- to five-day hospitalization. Complete recovery generally takes approximately four to six weeks. Simple hysterectomy is used to treat stage 0 (occasionally), and IA cervical cancers. All hysterectomies result in sterility (the inability to become pregnant).

Radical hysterectomy and pelvic lymph node dissection

A surgical procedure to remove the uterus, nearby tissues called the parametric and uterosacral ligaments, the upper section of the vagina and the pelvic lymph nodes. This surgery, which is generally used to treat cancers that have spread beyond the cervix, typically requires a five- to seven-day hospitalization. As with a simple hysterectomy, a woman will not be able to have a child following this procedure.

Pelvic exenteration

This surgical procedure removes the same organs and tissues as a radical hysterectomy as well as the bladder, rectum, vagina and part of the colon. Pelvic exenteration is used to treat locally advanced recurrent cancer of the cervix, and renders the patient sterile. It may also require additional procedures to account for the loss of normal bowel and bladder control.

Radical vaginal trachelectomy

Surgical procedure still considered experimental that removes only the cervix in early cases of cancer. This surgery may preserve a woman’s fertility, although studies have shown that some pregnancies achieved after trachelectomy have resulted in miscarriage or preterm labor.

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.

Prevention methods for cervical cancer

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.
Some states have introduced legislative bills requiring all girls receive the HPV vaccine as part of their routine school immunizations. However, there is great debate over whether the HPV vaccine should be mandatory.

Another way to prevent invasive cervical cancer is to undergo testing to detect HPV and precancers. Research has suggested that women ages 30 and older should receive an advanced HPV test in addition to a Pap test. However, additional studies are necessary to determine the benefits of such testing. Women should discuss the type and schedule of cervical screening tests with their gynecologists.

In women who exhibit cervical changes (dysplasia), precancer treatment can prevent the abnormal cells from developing into full cancer. According to the American Cancer Society (ACS), between 60 and 80 percent of newly diagnosed invasive cervical cancers are found in patients who have not had a Pap smear (a screening procedure that detects cervical changes before cancer develops) in the last five years.

The ACS has issued the following guidelines for early detection of cervical cancer

  • All women should be screened (tested) for cervical cancer when they reach 21 years of age, or three years after they first start having vaginal intercourse.
  • Starting at age 30, patients who have had three normal consecutive Pap tests may get screened every two to three years using the conventional Pap test or the liquid-based Pap test. Women with risk factors for cervical cancer, such as the human immunodeficiency virus (HIV), should continue to be tested annually.
  • Women over age 30, without cervical cancer risk factors, may choose to have a Pap test every three years in conjunction with an HPV DNA test, which determines whether the patient has HPV.
  • Women age 70 or older who have had three normal, consecutive Pap tests and no abnormal results in the past 10 years may choose to stop being screened for cervical cancer unless they have a history of cervical cancer or risk factors for the condition.
  • Patients who have had a total hysterectomy (surgical removal of the uterus and the cervix) may also choose to stop being screened for cervical cancer, unless the hysterectomy was performed because of cervical precancer or cancer. Those who had a simple hysterectomy (surgical removal of the uterus) should follow the guidelines detailed above.

Certain factors can affect the accuracy of the Pap test.

To help make the Pap test as accurate as possible, patients should:

  • Avoid scheduling appointments during their menstrual period.
  • Avoid douching for two days (48 hours) before the test.
  • Avoid having sexual intercourse for 48 hours before the test
  • Avoid using vaginal creams and medications, tampons, birth control jellies and foams for 48 hours before the test.

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

The categories of this system include:

  • Negative for intraepithelial lesion or malignancy, which means that no signs of precancer or cancer were found.
  • Epithelial cell abnormalities, which means that the cells that line the cervix show changes that might indicate precancer or cancer.
  • Other malignant neoplasms, which indicates that the patient may have another form of precancer or cancer that rarely affects the cervix.

Staging cervical cancer

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.

Questions for your doctor on cervical cancer

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about cervical cancer:

  • What signs might indicate precancerous or cancerous changes in my cervix?
  • What does an abnormal Pap smear mean?
  • What steps will follow an abnormal Pap?
  • What additional tests will I need to diagnose cervical cancer?
  • What are my treatment options?
  • Are these treatments successful in preventing precancer from becoming cancer?
  • Does cervical cancer spread easily?
  • What is the prognosis with my type and stage of cancer?
  • Will cervical cancer affect my fertility?
  • What can I do to prevent cervical cancer?
  • How often should I have a Pap test?