Cervical Dysplasia

Overview

Cervical dysplasia is a term used to describe the appearance of abnormal cells on the surface of the cervix, the lowest part of the uterus. These changes in cervical tissue are classified as mild, moderate, or severe. While dysplasia itself does not cause health problems, it is considered to be a precancerous condition. Left untreated, dysplasia sometimes progresses to an early form of cancer known as cervical carcinoma in situ, and eventually to invasive cervical cancer.

It can take 10 years or longer for cervical dysplasia to develop into cancer. Dysplasia can be detected from a Pap smear, the single most important step that a woman can take to prevent cervical cancer.

Mild dysplasia is the most common form, and up to 70% of these cases regress on their own (i.e., the cervical tissue returns to normal without treatment). Moderate and severe dysplasia are less likely to self-resolve and have a higher rate of progression to cancer. The greater the abnormality, the higher the risk for developing cervical cancer.

Cervical dysplasia does not cause symptoms; therefore, regular screening and early diagnosis are important. Detecting and treating dysplasia early is essential to prevent cancer. For this reason, most physicians quickly remove suspicious cervical lesions and require frequent Pap smears to monitor for recurrences.

Incidence and Prevalence

Every year, between 250,000 and 1 million women in the United States are diagnosed with cervical dysplasia. While it can occur at any age, the peak incidence is in women between the ages of 25 to 35. Most dysplasia cases can be cured with proper treatment and follow-up. Without treatment, 30% to 50% may progress to invasive cancer.

Risk Factors

Risk factors increase the frequency of occurrence. Several risk factors have been linked to dysplasia including multiple sexual partners, early onset of sexual activity, cigarette smoking, and sexually transmitted diseases, especially human papillomavirus (HPV) and HIV infection.

HPV Infection

Eighty to ninety percent of women with cervical dysplasia have an HPV infection. Human papillomavirus (HPV) is a group of more than 80 different viral strains. About one-third are sexually transmitted, and some types cause genital warts. HPV infects about 25 million people in the United States, and most of the viral strains are harmless.

However, the NIH Consensus Conference on Cancer of the Cervix and the World Health Organization (WHO) have concluded that several strains of HPV cause cervical cancer. The strains found most frequently in precancerous lesions and in cervical cancer are types 16 and 18. Other strains with high malignant potential include 31, 33, 35, 39, 45, 51, 52, 56, 58, and 68, and together, they account for almost 90% of cancerous lesions and dysplasia in HPV infections.

Most HPV infections resolve within 6 months and many women develop immunity. HPV often does not cause symptoms. One study found that nearly one-half of the women infected with HPV had no symptoms and a person may not even know that they are infected. Untreated HPV can result in recurrent and persistent cervical dysplasia and many experts believe that HPV is the main cause for changes in cervical cells that result in dysplasia.

HIV Infection

Women who are infected with HIV are at a greater risk for developing dysplasia. The risk appears to increase as the number of CD4 cells (cells that play a critical role in immune responses) decreases. HIV-positive women also have a higher rate of persistent HPV infections and may be infected with the strains that are associated with severe dysplasia and cervical cancer. Women whose immune systems are suppressed for other reasons, such as by drugs that prevent rejection of organ transplants, are also at greater risk. This suggests that women with weakened immunity are more likely to be infected with HPV and to have a persistent infection that does not resolve on its own.

Smoking

Nicotine and cotinine, chemicals produced from tobacco, have been found in the cervical cells of women who smoke. Men who smoke also excrete these chemicals in their semen, which comes in contact with the cervix during sexual intercourse. Tobacco chemicals may cause alterations in the cells that lead to dysplasia. (See also: women and smoking, and smoking cessation options)

High-risk Sexual Behavior

Having multiple sex partners, having sex with a man who has had multiple sex partners, and engaging in sexual intercourse before the age of 18 are linked to cervical dysplasia. Women in these categories have a greater chance of being infected with HPV or HIV, especially if they do not use a barrier contraceptive such as a condom. These infections put them at higher risk for developing cervical dysplasia.

DES Exposure

Between 1938 and 1971, approximately 5 million pregnant women were prescribed diethylstilbestrol (DES), a synthetic estrogen thought to help prevent miscarriage. Its use was discontinued when researchers found it to be ineffective and dangerous. The daughters of women who took DES have a higher risk for developing rare cancer of the vagina or cervix, called clear cell adenocarcinoma, and abnormalities of the cervix, vagina, and uterus.

Poor Nutrition

There is growing evidence that certain vitamins, such as folic acid, play a role in cervical health. A poor diet may also cause the immune system to weaken, decreasing the body's ability to fight viruses such as HPV.

Oral Contraceptives

Some research shows that women who use oral contraceptives may be at a higher risk for developing cervical dysplasia. However, it is not clear if the risk is directly attributable to the contraceptives themselves. One reason may be that oral contraceptives interfere with folic acid metabolism in the cells around the cervix, and folic acid may help prevent or improve cervical dysplasia. Another reason may be that women using this method of birth control may have increased exposure to sexually transmitted diseases, compared to those who rely on a barrier method such as a condom.

Signs of Cervical Dysplasia

Cervical dysplasia does not cause symptoms. Signs and symptoms, if any, are caused by an accompanying infection.

Pap Smears

The Pap smear is the most important diagnostic procedure for detecting cervical dysplasia. It is a simple and painless test that may cause minor discomfort.

Normal vaginal discharge contains cells that are shed from the cervix and uterus. A gynecologist or other health care practitioner removes some of these cells by brushing or scraping the cervix with a small instrument designed for this purpose. The cells are placed on a glass slide and sent to a laboratory, where they are examined under a microscope for changes and abnormalities.

The Pap smear is not 100% reliable. It produces incorrect results in about 15-25% of cases. Cervical cancer is missed in about 5% of cases. Reasons for incorrect results include the following:

Human error (The test should be done by an experienced practitioner and sent to a reputable laboratory.)
Inadequate number of cells in the sample
Presence of menstrual blood in the sample
Temporary changes in cervical cells caused by medications, pregnancy, infection

If atypical cells are found, the physician may recommend further testing.

HPV Test

Because of the association between human papillomavirus (HPV) and cervical cancer, this test can help determine the next step for a woman with atypical cells. This test checks for HPV genetic material, or DNA, within the cervical cells. A swab of cervical cells is taken and the specimen is sent to a laboratory and examined for HPV. If the HPV test is positive for a high-risk strain, the lesions are more likely precancerous. If the test is negative, the cervical changes are more likely benign.

Colposcopy

Depending on the severity of the dysplasia, results of the HPV test, and other risk factors, colposcopy is the next step in the diagnostic process. Generally, a colposcopy is performed if the cervical cells are distinctly abnormal.

This relatively simple procedure takes about 10 to 15 minutes to perform. A solution of diluted acetic acid (vinegar) is applied to the cervix to remove mucus and highlight abnormal cells. Using a bright light and a special electronic microscope (called a colposcope), the physician is able to see small areas of the cervix and vagina. The acetic acid and the lens of the colposcope make abnormal cells appear white and normal cells appear pink. If abnormal cells are seen, a biopsy is usually done.

Cervical Biopsy

A cervical biopsy usually is performed when the colposcopy reveals abnormal tissue. Using a small biopsy forceps, a tiny sample of abnormal tissue is removed from the cervix and sent to a laboratory for examination. More than one sample may be taken, depending on the amount of abnormal tissue detected by colposcopy.

Another type of biopsy, called an endocervical curettage, may also be done. This procedure is performed if the physician is unable to determine if the abnormal cells go beyond the surface of the cervix. Using a small-spoon shaped instrument called a curette, cells from inside the cervix are biopsied. The procedure takes about 10 to 15 seconds, but it can trigger uterine cramping.

A procedure called dilatation and curettage (D & C) may be performed if the physician suspects that abnormal cells extend beyond the cervix. A curette is used to remove cells from the cervical canal and the lining of the uterus. This procedure requires local anesthesia.

Treatment is based on the biopsy results.

Cervical Dysplasia Staging

Since the Pap smear was introduced in 1943, a number of methods have been developed to classify the results. The two methods commonly used today are the Bethesda System and the CIN Grading System.

The Bethesda System was developed by the Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH) in order to have a comprehensive and standardized method of classifying Pap smear results. It uses the term squamous intraepithelial lesion (SIL) to describe abnormal changes in the cells on the surface of the cervix. Squamous refers to thin, flat cells that lie on the outer surface of the cervix. An intraepithelial lesion occurs when normal cells on the cervical surface are replaced by a layer of abnormal cells, and these changes are classified as high grade or low grade.

Bethesda System

Atypical squamous cells of undetermined significance (ASCUS)—Borderline, some abnormal cells
Low-grade intraepithelial lesions (LGSIL)—Mild dysplasia and cellular changes associated with HPV
High-grade squamous intraepithelial lesions (HGSIL)—Moderate to severe dysplasia, precancerous lesions, and carcinoma in-situ (preinvasive cancer that involves only the surface cells)
Squamous Cell Carcinoma

Cervical Intraepithelial Neoplasia

(CIN) refers to new abnormal cell growth. Intraepithelial refers to the surface layers of the cells. The CIN System grades the degree of cell abnormality numerically, CIN I is the lowest and CIN III is the highest.

CIN Grading System

Atypia - correlates with ASCUS
CIN I - mild dysplasia and correlates with LGSIL
CIN II - moderate dysplasia and correlates with HGSIL
CIN III - severe dysplasia and correlates with HGSIL
Carcinoma in-situ
Cervical cancer

Treatment

Treatment of cervical dysplasia depends on the severity, the presence of HPV, risk factors, and patient's preference. For ASCUS and mild dysplasia (low-grade SIL/CIN I), the physician may perform HPV typing. If no virus or a low-risk strain is present, Pap smears may be repeated at 4- to 6-month intervals because ASCUS and mild dysplasia often resolve without intervention.

If a high-risk strain of HPV is present, colposcopy and biopsy may be indicated and treatment depends on the results of the procedures.

High-grade lesions require treatment. There are several methods available to remove the abnormal tissue, including electrocauterization, cryosurgery, laser vaporization, and surgery.

Electrocauterization

Loop electrosurgical excision procedure (LEEP) emits low-voltage, high-frequency radio waves through a thin loop of wire. Electrical current quickly and safely cuts away abnormal tissue. The procedure takes about 10 to 30 minutes and is performed in the doctor's office or as an outpatient in the hospital. LEEP allows the removed tissue to be examined by a pathologist to ensure that the lesion was completely removed and provide an accurate assessment.

Cryosurgery and Cryocauterization

These are relatively safe and simple procedures. In cryosurgery, the physician uses a carbon dioxide-cooled probe (called a cryoprobe) to freeze and kill abnormal cells. The tissue then sloughs off. It is performed in the physician's office. In cryocautery, an electric probe is used to cauterize the abnormal cells. These procedures do not allow abnormal tissue to be saved for pathological examination.

Laser vaporization or ablation

This procedure is performed in the hospital under general or local anesthesia. A laser is used to destroy abnormal surface cells. As with cryosurgery, it is impossible to obtain a specimen for pathologic examination. This procedure may cause less cervical scarring than cryosurgery. Cervical scarring makes the cervix more difficult to visualize.

Cone biopsy

This therapy is used to diagnose and remove abnormal tissue. A cone-shaped tissue sample is surgically removed from the cervix under general or spinal anesthesia in an operating room. The specimen is sent to a pathologist for detailed microscopic examination. If dysplasia is found, no further therapy is needed, provided all of the affected cells were removed. If cancer is found, additional treatments are indicated. The cone biopsy is usually performed for high-grade dysplasia, dysplasia that recurs, and suspected cancer.

Screening

The Pap smear is used to screen for cervical changes. Although Pap smears effectively reduce the incidence of cervical cancer, there is an ongoing debate about how often the test should be performed. Guidelines and recommendations vary.

A Pap smear is recommended for all women when they reach the age of 18 or become sexually active, whichever occurs first. After that, a number of factors affect the frequency of screening. The American Cancer Society recommends that women who have three negative Pap smears in 3 consecutive years may have them less often, depending on general health and sexual activity.

The NIH Consensus Conference on Cervical Health recommends that Pap tests can be done less often (after three consecutive negative results) if the patient is low risk. Low risk means no more than two lifetime sexual partners and a partner with no more than two lifetime partners. Most women should continue to have a yearly Pap smear.

A history of cervical dysplasia, genital warts, HIV infection, and in utero DES exposure may warrant Pap smears at more frequent intervals. Women should discuss screening frequency with their physicians.

Prognosis

The prognosis for cervical dysplasia is excellent. About 70% of mild dysplasia cases resolve on their own, and most dysplasia is curable with proper treatment and follow-up.

Prevention

Women can minimize risk for cervical dysplasia and reduce the chances of developing cancer by taking these preventative measures:

Pap smear - A Pap smear screens for changes in cervical tissue. Identifying dysplasia early may prevent it from developing into cervical cancer.
Avoid high-risk sexual behavior - Practicing monogamy or limiting the number of sexual partners decreases exposure to STDs, as does consistent use of condoms or other barrier methods. Sexual contact can transmit the HPV virus and condoms do not offer full protection against the virus. While HPV may cause genital warts, it often remains asymptomatic and undetected.
Smoking cessation - Cigarette smoking is associated with changes in cervical cells.
Nutrition - The National Cancer Institute recommends that women consume 5 servings of fresh vegetables and fruits each day. Nutrients including beta carotene, folic acid, vitamin A, and vitamin C may protect against cervical dysplasia. Some experts recommend taking a multivitamin to ensure adequate intake of these vitamins.
Cervical cancer vaccine (e.g., Gardasil®, Cervarix®) - These vaccines are approved for use in girls and women between the ages of 9 and 26 (Gardasil) and 10 and 25 (Cervarix) to prevent certain types of HPV that can cause cervical dysplasia and increase the risk for cervical cancer

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