Cervical Cancer

August 3, 2011

Cancer of the uterine cervix is an important worldwide health problem. The cervix is the opening of the uterus at the top of the vagina. Death rates in the developing countries from this disease are similar to death rates from breast cancer and lung cancer. In the developed nations, the widespread use of screening tests such as the Pap smear has both reduced the number of women getting the disease and improved the chances of surviving the disease. In this entry, we will review the risk factors for cervical cancer and its precursor, cervical dysplasia, the screening methods available, and the basics about the symptoms of cervical cancer and its treatment.

RISK FACTORS

Many women are not aware of the fact that cervical cancer is essentially a sexually transmitted disease.

Research has shown that a family of viruses called human papillomavirus (HPV) can infect the cells of the genital tract, and in some cases will lead to cancerous changes of those cells, particularly in the cervix. While almost all cervical cancers are caused by HPV, the great majority of women infected by HPV will never develop cancer.

The risk factors for cervical cancer are therefore the same as those for sexually transmitted infections such as: early age at first intercourse, multiple sexual partners, or having a partner with multiple sexual partners. Other risk factors may be due to impairment of the body’s immune system from fighting the HPV infection such as: HIV infection or AIDS, immune suppressive drugs (such as those taken by patients who have undergone an organ transplant), and smoking.

HPV infections often occur without causing any symptoms. In some cases, a patient may develop small warts on the external genital area. Problems in the cervical cells leading to cervical cancer can take years to occur, or in many women will never occur at all.

CERVICAL DYSPLASIA

After a woman becomes infected with HPV, the virus can enter the cells of the zone of the cervix called the “transition zone.” This is the area where lining-type cells of the vagina and cervix (squamous cells) join with the glandular cells in the inside canal of the cervix. This process can result in cervical dysplasia, which is the specific condition which is screened for with the Papanicolaou test, or Pap test. Although the Pap test is designed to look for dysplasia, it can also be read as “abnormal” due to other changes such as inflammation or the changes due to hormone shifts after menopause. For that reason, when a Pap smear is abnormal, an examination of the cervix with a microscope called a colposcope and actual biopsies of the cervix are done. Those biopsies will determine whether dysplasia changes are present, and whether they are mild, moderate, or severe.

Mild dysplasia, also called cervical intraepithelial neoplasia-1 (CIN-1), is often a temporary reaction to an HPV infection, and in 70% of cases will resolve with no treatment. Moderate dysplasia (CIN-2) and severe dysplasia (CIN-3) are less likely to resolve on their own, and therefore have the potential to progress to cancer. That process of progression takes 5-15 years, so the effective identification and subsequent treatment of

CIN-2 and CIN-3 can prevent the development of cervical cancer in most women.

Treatment for cervical dysplasia often involves removal of the transition zone area of the cervix in an outpatient procedure called loop electrocautery excision procedure (LEEP), and is highly effective.

Another test that is used for screening is actually swabbing the cervical area and testing for the HPV virus. This test has been shown to be able to identify women who do not need to proceed with colposcopy and biopsies when the Pap smear has only a mild abnormality. In addition, it may be used in women over 30 in conjunction with the Pap test as a more effective predictor of risk for cervical cancer.

SYMPTOMS OF CERVICAL CANCER

Cervical dysplasia causes no symptoms in most women. In women with undetected or untreated cervical dysplasia over a period of time, those abnormal cells can develop the ability to invade other tissues and at that point are defined as a cancer. Invasive cervical cancer causes symptoms such as irregular vaginal bleeding, bleeding after sexual intercourse, or a bloody or foul-smelling vaginal discharge. Symptoms of more advanced disease include pelvic or back pain or swelling in the legs.

STAGES

All cancers are assigned a stage which is a representation of how advanced it is when it is diagnosed. The stage helps to determine both the treatment options and the prognosis. In cervical cancer, Stage I disease refers to cancer that has not progressed beyond the cervix. There are substages such as IA and IB to help differentiate between tumors that are microscopic in size versus tumors that may be very large, but still confined to the cervix. Stage II refers to cervical cancer that has spread off of the cervix onto the upper vagina or into the soft tissues that support the uterus and cervix at the sides, called parametria. Stage III applies when the cancer has spread farther down to the lower vagina, or out farther into the parametria to the side of the pelvis. Stage IV is the most advanced and applies when other organs such as the bladder or rectum, or distant from the cervix such as the liver or lungs, are involved.

When a woman is diagnosed with cervical cancer, various tests will be performed to help determine the stage. These include a thorough pelvic examination, including a rectal examination, chest x-rays, blood tests, and often a CT scan of the abdomen and pelvic area. After her doctor determines her stage, the treatment options will be outlined. In some cases of advanced disease, surgery will be used to obtain more information prior to making a treatment plan. This may include cystoscopy (looking in the bladder with a telescope), proctoscopy (looking in the rectum with a telescope), or a more major surgery to remove lymph nodes that might be affected by the cancer.

TREATMENT

In the earliest cases of invasive cervical cancer, when there has been only minimal microscopic invasion of the cervix, the doctor may recommend a vaginal or abdominal hysterectomy (removal of the cervix and uterus, but not necessarily ovaries), or a cone biopsy, which is a cone-shaped removal of the outer cervix. Cone biopsy is usually used when a woman would like to preserve the possibility of childbearing. These are highly effective treatments and result in cure rates over 95%.

If the cancer is not microscopic, but is still confined to the cervix or upper vagina (Stages I and IIA), treatment options include radical hysterectomy with lymphadenectomy or combined pelvic radiation with chemotherapy. Radical hysterectomy involves removal of the uterus and cervix with the surrounding tissues of parametria and upper vagina together with the pelvic lymph nodes. Radiation includes external treatments to the whole pelvic area and internal treatments directly to the cervix, combined with a regular dose of chemotherapy to help the radiation work more effectively. Either of these treatments is effective in early stage disease, and one is generally selected based on other factors such as risks for surgery or radiation. In some centers in the United States, Canada, and Europe, an option to preserve fertility is available called the radical trachelectomy. This is a removal of the cervix with the parametria and upper vagina with the lymph nodes, but the remainder of the uterus is left behind, and can potentially be used for childbearing. This procedure may not be possible in all women with this stage of disease, but in selected women can be effective.

For all other stages of cervical cancer (Stages IIB-IV), the treatment that has been shown to be the most effective is radiation combined with chemotherapy. This is performed as was described for early stage disease, but may be given to a higher dose level or even to a wider area.

In some cases, a woman may undergo radical hysterectomy designed to be the definitive treatment, but then may require radiation after surgery due to findings at the time of surgery, such as cancer spread to the lymph nodes.

OUTCOME

Women with microscopic forms of cervical cancer have very high possibilities of survival—close to 100%. Once the cancer is visible, in the early stages (IB and IIA), the chances of surviving average about 85%. Stage IIB will have a 65-70% survival rate, whereas Stage III will have a 24-40% chance of survival, and Stage IV only 5%. Surgical options, the side effects from surgery and radiation, and the management of symptoms have all improved so that many women who undergo treatment for this disease are able to recover complete function and do not suffer from lasting side effects. The most important aspect of reducing the impact of cervical cancer, however, will be to detect and treat cervical dysplasia before it has the opportunity to progress. In the future, there may be a vaccine available to reduce the risk of infection with the HPV virus, or to help the immune system fight the HPV infection and decrease the risk of developing dysplasia or cancer.

SEE ALSO: Cancer screening, Colposcopy, Diethylstilbestrol, Genital warts, Human papillomavirus, Hysterectomy, Pap test, Pelvic examination

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