Volume 4 Number 3 1992

In theory, many consider invasive cervical cancer a completely preventable disease. Factors such as the widespread availability of screening programs like the Pap smear, successful treatment for carcinoma before it spreads from the cervical lining and a precancerous "buffer" period of eight to twenty years all support the idea that cervical cancer incidence and mortality are avoidable. However, in practice, it is estimated that 13,500 women in the U.S. will be diagnosed with primary cervical cancer in 1992 and of these, 7,500 will die. While this accounts for only 2.5 percent of all cancers that afflict American women, the incongruity of fact and theory have led researchers to search for important characteristics in the epidemiology of cervical cancer and to evaluate screening techniques.

Age

Similar to many cancers, the older a woman gets, the more likely her chances of developing cervical carcinoma. The peak years of incidence are between 45 and 55; however, in recent years a second peak has emerged in the 30 to 35 year age group. The severity of dysplasia, or abnormal changes in cells that are the first warning signs for cervical cancer, increases with age. Dysplasia mostly occurs in women who are about 30 years of age. It then may develop into carcinoma-in-situ (CIS), which occurs when the abnormal cells penetrate the outer layer of the cervix. The peak age for CIS is 36, whereas the peak age of overt cancer, the next stage, occurs at age 48. A carcinoma is considered invasive when it spreads from the lining of the cervix into the cervical body.

Marital History

Early sexual activity has long been associated with increased rates of cervical cancer. A study by Lombard and Potter in 1950 found that woman who married before the age of 20 had twice the risk of developing cervical cancer as those who married later. In addition, a 1952 study of 13,000 nuns found no cases of carcinoma of the cervix. These studies and others published to date emphasize the same theme: the importance of sexual history. Much of the epidemiologic data reported suggests cervical carcinoma to be venereal in origin with incidence increasing relative to the number of sexual partners. A 1981 study found that women married to men whose previous wives died of cervical cancer had three times the risk of developing carcinoma of the cervix regardless of their past history. This supports the belief that there must be an organism or substance passed through intimate contact associated with the development of cervical cancer.

Viral Etiology

In the mid-seventies and eighties, HSV II, a virus that could be isolated from cervical tumors, generated significant interest as an etiological agent. Blood specimens of patients with cervical cancer showed evidence of an antibody to HSV II; however, a cause and effect relationship was never established. Today, this virus is believed to play a lesser role in the development of precancerous changes in the cervix as well as cervical cancer. Researchers now believe that the Human Papilloma Virus (HPV) is either the cause or a strong etiological cofactor in the development of this carcinoma.

HPV, also a factor in genital and skin warts, is considered to account for 90 to 95 percent of cervical cancer and preinvasive disease. It is present in epidemic proportions in the U.S. with estimates of infection in sexually active people ranging from 20 to 40 percent of the population. Over 40 viral subtypes have been identified, but only a few of these are found in various stages of cervical disease. Infection from a particular subtype does not guarantee malignancy, for in some instances, a woman with HPV will develop neither warts nor cancer. A 1991 study found that with exposure to both HPV and tobacco smoke, mice had a greater tendency to develop malignancies that resembled human cervical cancer than if either exposure were present by itself.

Ethnicity

Jewish women seem to be at relatively low risk for cervical cancer, leading some to suggest hygiene, heredity and circumcision as explanations. When sexual practices and number of sexual partners are controlled for, though, there is no difference in incidence. Thus, the reduced prevalence probably represents a reduced exposure to HPV.

Blacks have been found to be twice as incident as other races for cancer of the cervix. Many factors are involved, including sexual behavior, nutrition, socioeconomic class, history of venereal disease and access to screening.

Other Associations

Individuals who have suppressed immune systems, either through pharmacological means (i.e., corticosteroids) or other diseases (AIDS, cancer, transplant) have accelerated growth of preinvasive lesions and confer a higher incidence of cervical malignancy. Altered immune response has been found in patients who lose their natural ability to fight endogenous cancer.

Tobacco use has consistently been associated with incidence rates that are 1.5 times greater than controls. Such rates generally occur in women who smoke heavily.

More controversial, however, is the relationship with oral contraceptive use. Early investigations suggested this link, but the studies were flawed by lack of attention to sexual history. In a more carefully designed investigation, Swan (1981) found that long-term use of oral contraceptives was associated with an increased risk of cervical cancer, but only in those groups of patients with already known risk factors.

Screening

The Papanicolau (Pap) smear, introduced in 1943, remains the mainstay of cervical cancer screening around the world. The test involves scraping cell samples from the outer portion of the cervix (the lower part of the uterus) and the endocervical canal (inside the cervical opening).

This test was designed as a cost effective way to evaluate large numbers of people reliably and reproducibly. However, routine Pap smear will miss up to ten percent of cervical carcinomas because of errors made while acquiring the sample, pathological misinterpretation at the laboratory or the inability to detect certain types of pathology.

While there is a general consensus that appropriate evaluation can diagnose early cell changes and lead to definitive treatment of precancerous stages, there is little agreement about what "appropriate evaluation" means. The American College of Obstetricians and Gynecologists (ACOG) recommends that a Pap smear be done for all women by the age of 18 or when sexually active, whichever comes first. Follow-up evaluation should be done annually in women with multiple sexual partners. The ACOG also recommends that those in long-term relationships who have had three negative annual Pap smears in a row may be screened less often.

Cervical carcinoma remains one of the most curable forms of gynecologic cancer, especially if diagnosed early. In general, cure rates using either radiotherapy or surgery in early cancers of the cervix range from 85 to 95 percent. Nevertheless, the incidence remains high for a carcinoma thought to be "completely preventable." As a result, screening, in order to prevent a precancerous stage from developing further, takes on a greater importance. Regular Pap smears and follow-up, especially in women who have HPV or multiple sex partners, is the most effective way to prevent cervical cancer.

Robert L. Coleman, M.D., is a Junior Faculty Associate in the Department of Gynecology at the University of Texas M.D. Anderson Cancer Center in Houston.