Cervical Cancer

Description An in-depth report on the causes, diagnosis, treatment, and prevention of cervical cancer.

Alternative Names Dysplasia; Human Papillomas Virus; Pap Smear

Treatment for Invasive Cervical Cancer Radiation therapy and surgery are about equally effective as a single option for treating very small cervical cancers in their earliest stages, with survival rates of up to 85% to 90% in appropriate patients. Factors influencing the choice between radiation therapy and surgery in women with invasive cancer include the patient's age and health and the extent of the disease. Both surgery and radiation therapy eliminate the possibility of having children in premenopausal women. Although treatments for cervical cancer have several potentially severe side effects, they are usually well-tolerated. Women undergoing any of these treatments should feel free to seek support groups and counseling, which can be as important for their outlook as medical therapies.

Surgery

In the early stages of cervical cancer, surgery is often the preferred primary treatment approach since it preserves normal sexual function. Surgery for invasive cancer is nearly always hysterectomy. Some patients desiring fertility who have early stage I cancer may be candidates for cervical cone biopsy.

Hysterectomy. A hysterectomy attempts to eliminate the cancerous tissue by removing the uterus. There are several variations of this operation, depending on the location of the tumor. In women of childbearing age, the ovaries can usually be left intact. Although a woman who has a hysterectomy but retains her ovaries cannot bear children, she will not go into premature menopause. (Studies indicate that leaving the ovaries intact is safe for most women and does not pose any greater risk for cervical cancer recurrence.)

A simple hysterectomy involves the removal of the uterus and the cervix, but leaves the parametrium (tissue surrounding the uterus) and vagina intact. Lymph nodes in the pelvis are not usually removed.

Click the icon to see an illustrated series detailing a hysterectomy.

A radical hysterectomy removes not only the uterus and the cervix but also the parametrium, the supporting ligaments, the upper vagina, and some or all of the local lymph nodes (a procedure called lymphadenectomy).

If the cancerous tumor recurs within the pelvis after primary treatment, a more extreme procedure may be performed called a pelvic exenteration, which combines radical hysterectomy with removal of the bladder and rectum. (In such cases, plastic surgery may be needed afterward to recreate an artificial vagina.) Patients undergoing this procedure are physically and psychologically screened in advance to determine whether it is an appropriate choice. The success rate for pelvic exenteration in halting the progression of the disease is approximately 25% to 45%.

Any form of hysterectomy is major surgery and requires at least a three to five day hospital stay. Although hysterectomy typically uses a wide abdominal incision, less invasive techniques that allow shorter recovery time may be possible for some women with early stage cancers if performed by experienced surgeons.

Side effects include difficulty emptying the bladder or bowels and a painful lower abdomen. Urinary tract infections are very common. Complications include fistulas (abnormal channels within the pelvis, which in this case are a result of surgery), bladder dysfunction, and cysts.

Normal activity, including intercourse, can be resumed in about four to eight weeks. Once the uterus is removed, menstruation will cease. If the ovaries are removed, the symptoms of menopause will begin. These symptoms are likely to be more severe in surgical menopause than in the course of a natural passage to menopause. Hormone replacement therapy should be considered. [For more information on hysterectomy see the Well-Connected Report #73, Fibroids: Uterineor Report #74, Endometriosis.]

Trachelectomy.An experimental procedure called trachelectomy is being investigated for preserving fertility in certain women in early stage cancer, but it is highly controversial and appropriate in only about 5% of cervical cancer patients. In the procedure, only the cancerous portion of the cervix is removed, while the uterus and the rest of the cervix are left intact. The cervix is closed with a suture.

Small, early studies suggest it may be effective for early stage 1 patients with no risk factors for aggressive cancer. In two small 1999 and 2000 studies, conception rates were between 27% and 37%, and survival rates after two years were over 95%. The procedure is primarily performed outside the US, and few American surgeons are skilled in this surgery at this time. Throughout the world, in fact, only about a few hundred of these procedures have been performed to date. Women should also realize that conception rates are still lower than normal. And even if they can get pregnant, there is a very high risk for miscarriage because the cervix is weakened. Larger and longer-term studies are needed to confirm its long-term safety.

Radiation

Radiation therapy is an alternative approach for early stage cervical cancer. Radiation with concurrent with cisplatin-based chemotherapy is now the standard treatment for locally advanced cervical cancer. Radiation therapy employs high-energy rays aimed at the body from an outside machine (external beam radiation) and radioactive materials placed inside the body against the cervix (intracavitary radiation).

• External beam radiation is given first and aimed at the lymph nodes along the pelvic wall. It usually involves a short period of direct-radiation five days a week for about six weeks in an outpatient setting.
• Intracavitary radiation (also called brachytherapy) follows and is designed to deliver high doses of radiation to the local tumor area. Radioactive material, typically cesium-137, is encapsulated in both gold and platinum. These capsules are inserted in a long stainless steel tube, called a tandem, which is inserted in the uterus and in small stainless steel cylinders, called colpostats, which are placed against the cervix as close to the cancerous cells as possible. Commonly, two or more radiation treatments are administered for about 35 hours each time. Radiation implants may also be inserted directly into the tumor using a needle.

In order to be effective, radiation therapy must be powerful enough to destroy the cancer cells' capacity to grow and divide. This means that normal cells are also affected, which may cause significant side effects. Fortunately, healthy cells usually recover quickly from the damage, whereas abnormal cells do not.

Advanced methods for targeting radiation more precisely are now available that limit the damage to healthy tissue. They include 3-D conformal radiation and intensity-modulated radiation therapy (IMRT):

• 3-D conformal techniques use computers and a three-dimensional image of the cervix to provide precise targeting of the tumor using multiple high-dose radiation beams.
• IMRT also uses 3-D techniques and employs very thin and precise beam at various intensities.

Side Effects. Side effects of radiation therapy include fatigue, redness or dryness in the treated area, diarrhea, frequent or uncomfortable urination, and vaginal dryness, itching, or burning. After treatment, side effects usually disappear.

Long-Term Complications. Complications include proctitis (inflammation of the rectum) and cystitis (inflammation of the bladder). Bowel obstruction is an uncommon complication. Radiation therapy may also cause vaginal scarring, sexual difficulties, and premature menopause in younger women. Occasionally an abnormal tunnel between the bladder and the vagina, known as a vesicovaginal fistula, will develop and may require surgery.

Click the icon to see an image of the female anatomy.

Investigative temporary silicone implants or a noninvasive device called the belly board may protect the small intestine during radiation therapy and help reduce complications.

Radiation itself may increase the risk for later development of cancer in the area surrounding the treated tissue. Although newer more precise radiotherapy approaches should reduce this risk, there is some concern that IMRT may double the incidence of secondary cancers over time compared to 3-D conformal techniques. This is of particular concern in younger patients.

Radiation and Hyperthermia. Investigators are studying hyperthermia (use of high heat often provided by ultrasound) in combinations with radiation therapy. This approach has shown some promise in achieving significant response rates in small studies. Comparison studies are important to determine if this approach would be as beneficial with radiation therapy as concurrent chemotherapy.

Chemotherapy

Chemotherapy employs cell-killing drugs, known as cytotoxic agents, to destroy widespread cancer cells that have spread from their point of origin (the primary tumor) and are, therefore, no longer treatable by surgery or radiation.

For many years, chemotherapy was only used with very advanced disease to reduce symptoms. Platinum-based chemotherapy agents (usually cisplatin) are now being used in many situations for cervical cancer including the following:

• In combination with radiation therapy to improve survival rates in certain women, including some with locally advanced cancer.
• In some women with locally advanced cancer to reduce tumors to the point where the cancer may be operable.
• When cancer has spread (metastasized), mostly to reduce symptoms such as pain.

Chemotherapy Agents Used.

• Platinum-Based Agents. One of the most active chemotherapeutic agents for cervical cancer is cisplatin, which enhances the effectiveness of radiation in the treatment of patients with more advanced disease stages. Cisplatin and carboplatin are known as platinum-based drugs. In general, platinum-based agents are the standard drugs used for this disease. Concurrent platinum-based agents and radiotherapy are important treatments for many later cancer stages. Even in treating metastatic disease, cisplatin used alone has been more helpful than even combinations of agents. There is some evidence that a combination of platinum plus paclitaxel with possibly other single agents may be more effective than platinum alone in the treatment of metastatic disease. Other platinum agents, such as nedaplatin, are under investigation.
• Drugs that Enhance Radiation. Some drugs being investigated appear to increase tumor response to radiation therapy, and so are known as radiation sensitizers or enhancers. Topotecan, a radioenhancer, for example, is showing some promise in early studies, although toxicity is high.
• Other Agents. Other drugs, mostly used in combinations, have also been investigated with some promise. They include with epirubicin, irinotecan, paclitaxel, bleomycin, mitomycin, vinorelbine, gemcitabine, and doxifluridine.

For cancer that has spread to other areas from its original source (metastatic disease), chemotherapy regimens may use single cytotoxic agents or several agents in combination.

Administration. Cytotoxic agents may be given orally or as injections. Treatment may be administered at a medical center, physician's office, or even a patient's home. Some patients receiving chemotherapy may need to remain in the hospital for several days so the effects of the drugs can be monitored. The drugs are often administered in cycles with a period of rest following a period of treatment in order to allow a recovery from the side effects.

Side Effects. Chemotherapy affects all fast-growing cells, including healthy ones, so some side effects are inevitable. Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include the following:

• Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects in nearly all patients given moderate drugs and most patients who take more powerful drugs. In one study, a combination of dexamethasone (a corticosteroid) with ondansetron taken within 24 hours of chemotherapy achieved either a major or complete reduction in nausea and vomiting.
• Diarrhea.
• Temporary hair loss.
• Weight loss.
• Fatigue.
• Anemia.
• Depression.

Complications. Serious short- and long-term complications can also occur and may vary depending on the specific agents used. They include the following:

• Increased chance for infection from suppression of the immune system.
• Severe drops in white blood cells (neutropenia). Certain agents, such as taxanes, pose a higher risk for this than other chemotherapeutic drugs. White blood cell count may be improved with the addition of a drug called granulocyte colony-stimulating factor (either filgrastim and lenograstim).
• Liver and kidney damage.
• Abnormal blood clotting (thrombocytopenia).
• Allergic reaction, particularly to platinum-based agents. (A simple skin test in under investigation that may identify people with a potential allergic response.).
• Menstrual abnormalities are common and premature menopause occurs in about 30% of women, particularly in those over 40.
• Rarely, secondary cancers such as leukemia.
• Between a quarter and a third of women report problems in concentration, motor function, and memory, which may be long-term. This effect may be due to reductions in estrogen levels after treatments.