INTRODUCTION

More than 11,000 American women develop cervical cancer each year. However, cervical cancer is a treatable condition and there is a good chance of cure if the cancer is found and treated in the early stages.

This article discusses the diagnosis and treatment of women with early stage cervical cancer. A separate article discusses the treatment of early stage cervical cancer in women who want to become pregnant in the future. (See "Patient information: Fertility preservation in women with early stage cervical cancer (Beyond the Basics)".)

THE CERVIX

The uterus (womb) opens into the vagina through the cervix (figure 1). Squamous cells make up the outer layer of the cervix. Squamous cell carcinoma of the cervix is the name for cancer that affects these cells.

The cervix also includes glandular (also called columnar) cells, which line the opening of the cervix and the canal that leads into the uterus (the endocervical canal). These cells can also become cancerous; when they do, they are called adenocarcinomas of the cervix. Although they arise from different types of cells, squamous cell carcinoma and adenocarcinoma of the cervix are treated similarly in the early stages.

CERVICAL CANCER RISK FACTORS

The most common risk factor for cervical cancer is infection with a virus called human papillomavirus (HPV). HPV is spread by direct skin-to-skin contact, including sexual intercourse, oral sex, anal sex, or any other contact involving the genital area (eg, hand to genital contact). HPV infection can also cause a noncancerous condition called condyloma (genital warts). (See "Patient information: Genital warts in women (Beyond the Basics)".)

Most HPV infections are temporary because the body's immune system effectively clears the infection. When certain types of the HPV virus persist in the body, there is a higher likelihood that the viral infection will cause cervical cell abnormalities such as dysplasia or cancer; persistent infections are believed to occur in 10 to 20 percent of women. Evidence of HPV infection can be detected in almost all cervical cancers (squamous cell carcinomas as well as adenocarcinomas). For more information about HPV testing, (see "Patient information: Cervical cancer screening (Beyond the Basics)").

Additional risk factors for cervical cancer include cigarette smoking and a weakened immune system (caused by certain diseases, medications, or HIV/AIDS).

CERVICAL CANCER SYMPTOMS

Typically, cervical cancers develop slowly over a period of several years. In some women, the cancer does not cause any symptoms, while in others it causes abnormal vaginal bleeding or discharge. This can include bleeding between menstrual periods, bleeding after sex, or bleeding after menopause. This bleeding may be no more than a spot of blood.

Abnormal bleeding can also be caused by a number of other conditions, not related to cancer. If you have abnormal vaginal bleeding, make an appointment to see your doctor or nurse.

CERVICAL CANCER DIAGNOSIS

Cervical cancer is diagnosed with a cervical biopsy. A biopsy involves removing a small piece of tissue. The biopsy is performed during an office visit using a procedure called colposcopy. The colposcope (similar to a large magnifying lens) magnifies the cervix. This allows the clinician to better see the location, extent, and degree of very small abnormalities that may not be visible with the naked eye alone. (See "Patient information: Colposcopy (Beyond the Basics)".)

The tissue obtained during the biopsy is analyzed with a microscope to see if cervical cancer cells are present. In some cases, a larger biopsy called cervical conization is needed (figure 2).

If a biopsy shows cervical cancer, you should see a doctor who specializes in cancers of the female reproductive system (called a gynecologic oncologist).

CERVICAL CANCER STAGING

Once cervical cancer is diagnosed, the next step is to determine its stage. Staging is a system used to describe the spread of a cancer. Cervical cancer is staged mainly based upon the results of physical examination, which includes a complete pelvic (internal) examination of the cervix, uterus, and ovaries. Other procedures may also be performed to evaluate how far the cancer has invaded within the pelvis. Patients may also be asked to undergo a chest x-ray or bone x-rays to detect whether the cancer has spread outside or distant to the pelvis. The most common sites of distant spread are the lungs and bone.

A cervical cancer's stage is assigned based on:

• The size of the cancer
• How deeply the cancer has invaded into the tissue surrounding the cervix
• If there are signs of cancer in the vagina, pelvis, or local lymph nodes (figure 3)
• If there are signs of cancer spread to other organs

Cervical cancer stages range from stage I (cancer is in the cervix or uterus only) to stage IV (the cancer has spread to distant organs, such as the liver). In general, lower stage cancers require less treatment than higher stage cancers.

Other imaging tests are often recommended to determine the best treatment approach, but the results do typically not change the stage. These include computed tomography (CT scan), magnetic resonance imaging (MRI), and/or positron emission tomography (PET scan).

CERVICAL CANCER TREATMENT OPTIONS

There are several options for treatment of early stage cervical cancer. Decisions about treatment depend on your age and health, the stage of the cancer, and you and your doctor's preferences.

The most common treatment for early stage cervical cancers is radical hysterectomy (surgical removal of the cervix and uterus). The alternative is radiation therapy, which is usually given in combination with chemotherapy. Some patients with the earliest stage cervical cancers can be treated with cervical conization or simple hysterectomy alone. (See "Patient information: Treatment of precancerous cells of the cervix (Beyond the Basics)" and "Patient information: Abdominal hysterectomy (Beyond the Basics)".)

It is not possible to become pregnant after having a hysterectomy or pelvic radiation therapy. In women with early stage cervical cancer, it is sometimes possible to have a less aggressive treatment, which would allow you to carry a pregnancy. These issues are discussed separately. (See "Patient information: Fertility preservation in women with early stage cervical cancer (Beyond the Basics)".)

Radical hysterectomy — Radical hysterectomy is a surgical procedure that involves removing the uterus, cervix, and some of the vagina (figure 4). The ovaries do not necessarily have to be removed during a hysterectomy; this decision depends on your age and other factors. (See "Patient information: Abdominal hysterectomy (Beyond the Basics)", section on 'Removal of ovaries'.)

The surgery is usually performed through an incision in the abdomen (figure 5). Alternately, surgery can be done through several small incisions using a laparoscope. The surgical approach depends on your surgeon's preference and other factors.

The surgery generally takes three hours. Most women stay in the hospital for two to three days after surgery.

If abnormal or cancerous cells are found at the margins (edges) of the tissue or lymph nodes that are removed, or if the tumor has other features that increase the risk that the cancer will come back, further (adjuvant) treatment is recommended. This generally includes both radiation therapy and chemotherapy.

Radiation therapy — Radiation therapy (RT) refers to the use of high-energy x-rays to stop the growth of the cancer. There are two ways to deliver radiation therapy: brachytherapy and external beam radiation therapy (EBRT).

Brachytherapy — Brachytherapy delivers radiation from a device that is temporarily placed inside the vagina. This delivers a high dose of radiation to the area where cancer cells are most likely to be found, with the hope of minimizing the effects of radiation on healthy tissues.

There are two types of vaginal brachytherapy: low dose rate and high dose rate.

• Low dose rate brachytherapy uses a device that delivers radiation through the vagina for two or three days, 24 hours per day. You stay in the hospital during this treatment.
• High dose rate brachytherapy also uses a device that delivers radiation through the vagina. However, the device is placed in the vagina for only for a few minutes at a time once a day, and treatment is generally repeated three to five times. This treatment is generally given as an outpatient, and women who get high dose rate brachytherapy do not have to stay in the hospital overnight. You can usually continue your normal daily activities during treatment.

External beam radiation therapy (EBRT) — With external beam radiation therapy (EBRT), the source of the radiation is outside the body, and the area to be treated (referred to as the radiation "field") is designed carefully to limit the amount of radiation directed at healthy tissue.

During EBRT, your body is positioned beneath the x-ray machine in the same way every day, and the radiation field is exposed to the radiation beam for a few seconds (similar to having an x-ray) once per day, five days per week for five to six weeks. This is done as an outpatient, and you can usually continue your normal daily activities during treatment.

Brachytherapy alone is adequate treatment for the earliest stage cervical cancers. In women with more advanced disease, EBRT is generally added to brachytherapy to decrease the chance of the cancer coming back [1].

Side effects of radiation therapy — Possible short term side effects of RT include:

• Feeling tired
• Needing to empty your bladder frequently
• Discomfort with urination
• Loose stools and feeling the need to have a bowel movement frequently
• Pubic hair falling out

Most of these problems resolve when treatment is completed.

Longer term side effects can include:

• Urine leakage
• Pain or bleeding with bowel movements
• Narrowing or scarring of the vagina, which can cause pain during sex

If you are sexually active, ask your doctor or nurse about specific things that you can do to prevent pain during sex after treatment. This might include using a vaginal dilator during and after treatment. (See 'Sexual issues after treatment' below.)

Chemotherapy — Most women who undergo EBRT for cervical cancer are given chemotherapy during the radiation therapy (an approach termed chemoradiotherapy). Chemotherapy drugs are medicines that stop or slow the growth of cancer cells.

Chemotherapy has the ability to enhance the damaging effect of radiation therapy on cervical cancer cells; when chemotherapy drugs are used in this manner, they are referred to as "radiation sensitizers". The chemotherapy is usually given in a vein (IV) once per week during the course of EBRT.

Support during treatment — Most women and families affected by cervical cancer worry about their short and long term health and the risk of the cancer coming back. You might continue to worry for many years after treatment ends.

It is important to talk openly and honestly with your family and healthcare team. Many women benefit from bringing a family member or friend to doctor visits; this person can help you to understand your options, ask important questions, take notes, and feel supported.

A variety of support options are available, both during and after treatment, including individual counseling, support groups, and Internet-based discussion groups. A list of reputable groups is available below (see 'Where to get more information' below).

CERVICAL CANCER PROGNOSIS

Each patient with cancer is different, and it is difficult to predict what an individual woman should expect in the future. The chances that early stage cervical cancer can be cured are good in most cases. When discussing chances of cure, it is important to remember that these numbers represent averages and do not necessarily predict what will happen to you.

The survival rates for women with early stage cervical cancer who have standard treatment are excellent. In the earliest stages (IA, confined to the cervix, no more than 5 mm deep and 7 mm wide) at five years after diagnosis, approximately 95 percent of women are alive. This means that 5 percent of women died, although the cause of death was not necessarily related to the cancer. For slightly larger cancers (IB1, confined to the cervix, less than 4 cm), approximately 90 percent of women are alive at five years after diagnosis.

CERVICAL CANCER FOLLOW UP

Monitoring — After cervical cancer treatment, periodic follow-up testing and examination are recommended. There is no established schedule of testing and follow-up visits. Based on research findings and recommendations of expert groups, this is our general approach to cervical cancer follow-up [2-4]:

• A careful physical examination every three to four months for two years, then every six months during years 3 to 5, and annually thereafter.
• Cervicovaginal cytology (Pap smear) annually.
• Annual chest x-ray for the first two to five years.
• Other tests, including blood tests, PET scans, pelvic ultrasound, intravenous pyelography, and MRI are not recommended for patients who have no symptoms that suggest a cancer recurrence.

Sexual issues after treatment — Changes after cervical cancer treatment may include vaginal shortening, narrowing, and decreased vaginal lubrication. In addition, women who were premenopausal before treatment may become postmenopausal as a result of pelvic radiation or chemotherapy. These physical changes impact sexual satisfaction because they may lead to pain during intercourse, lack of interest in sex, difficulty having an orgasm, and decreased frequency of sexual activity.

Using a vaginal moisturizer or lubricant during intercourse can relieve some of these bothersome symptoms. Counseling for sexual and/or psychological difficulties may also be helpful. If the vagina is severely narrowed, use of vaginal dilators may help. (See "Patient information: Sexual problems in women (Beyond the Basics)".)

CLINICAL TRIALS

Progress in treating cervical cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

• www.cancer.gov/clinicaltrials/learning/
• www.cancer.gov/clinicaltrials/
• http://clinicaltrials.gov/

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient information: Cervical cancer (The Basics)
Patient information: Human papillomavirus (HPV) vaccine (The Basics)
Patient information: Pap tests (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient information: Management of atypical squamous cells (ASC-US and ASC-H) and low grade cervical squamous intraepithelial lesions (LSIL) (Beyond the Basics)
Patient information: Management of high grade cervical squamous intraepithelial lesions (HSIL) and glandular abnormalities (AGC) (Beyond the Basics)
Patient information: Fertility preservation in women with early stage cervical cancer (Beyond the Basics)
Patient information: Colposcopy (Beyond the Basics)
Patient information: Treatment of precancerous cells of the cervix (Beyond the Basics)
Patient information: Abdominal hysterectomy (Beyond the Basics)
Patient information: Sexual problems in women (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Cervical intraepithelial neoplasia: Definition, incidence, and pathogenesis
Clinical trials of human papillomavirus vaccines
Epidemiology of human papillomavirus infections
Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis
Management of early stage cervical cancer
Management of locally advanced cervical cancer
Invasive cervical cancer: Staging and evaluation of lymph nodes
Management of recurrent or metastatic cervical cancer
HIV infection and malignancy: Epidemiology and pathogenesis
Overview of preventive medicine in adults
Preinvasive and invasive cervical neoplasia in HIV-infected women
Radical hysterectomy
Recommendations for the use of human papillomavirus vaccines
Virology of human papillomavirus infections and the link to cancer
Small cell neuroendocrine carcinoma of the cervix
Invasive cervical adenocarcinoma

The following organizations also provide reliable health information.

• American Society of Clinical Oncology

      (www.cancer.net/portal/site/patient)

• The Gynecologic Cancer Foundation

     (www.thegcf.org)

• National Comprehensive Cancer Network

     (www.nccn.com)

• Gynecologic Oncology Group

     (www.gog.org/gynecologiccancerinformation.html)

• National Cancer Institute

     1-800-4-CANCER
     (www.cancer.gov)

• American Cancer Society

     1-800-ACS-2345
     (www.cancer.org)

• The National Cervical Cancer Coalition

     (www.ncc-online.org)

Patient support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Cancer Forum

     (http://cancer.about.com/forum)

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