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Uterine CervixLouise A. Brinton, Ph.D.*
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The uterine cervix is the small cylindrical neck that leads from the uterus, or womb, into the vagina. A knob of the cervix protrudes into the vagina and can be visualized on physical examination. Cell samples are taken from this part of the cervix for the Pap smear test, which is used to detect cancer cells or changes in cell structure that may lead to cancer. The most commonly detected changes are dysplasias, which are thought to be precursor conditions for carcinoma in situ (CIS) and invasive cancer of the cervix. However, many dysplasias regress over time, and the factors that lead to progression are unclear.
In CIS, an outer layer of normal cells has been replaced by cancer cells. It is about 95 percent treatable and curable. In invasive cancer of the cervix, the cancer cells have invaded the underlying tissue of the cervix. CIS occurs most often among women 25 to 34 years of age, while invasive cervical cancer most often is diagnosed in women over the age of 50. Both incidence and mortality for invasive cancer of the uterine cervix have declined steadily in this country over the past three decades (Devesa et al., 1989). Nevertheless, black women continue to experience incidence rates that are nearly two times higher than those in whites. Racial differences are also evident in survival statistics; blacks have a 56 percent five-year relative survival rate compared with 70 percent for whites (Ries et al., 1994). The racial differences may be due, in part, to the association of cervical cancer with the sexual and other behavioral characteristics of low socioeconomic status. High rates for cervical cancer are found in the American South, particularly in Appalachia. The U.S. incidence rates are generally low, however, compared to other parts of the world, such as India and South America, which have world standardized rates over 40 per 100,000. The comparable world standardized rate for U.S. black women is 12 and, for white women, 7 per 100,000 (Parkin et al., 1992). Sexual behavior has been identified as the major risk factor for both CIS and invasive cervical cancer (Brinton and Fraumeni, 1986). Risk of both conditions is increased in women reporting either early age at first intercourse or numerous lifetime sexual partners. Early onset of sexual activity is thought to be associated with high risk because, during puberty, cervical tissue undergoes a variety of changes that may make the area more vulnerable. Because early intercourse is usually correlated with the eventual number of sexual partners, several studies have attempted to disentangle the two factors. They have found that the greater the number of sexual partners, the greater the risk of sexually transmitted disease; consequently, much research has focused on the role of a variety of sexually transmitted agents. Further supporting sexually transmitted agents in the etiology of this disease are several studies which indicate that there may be an important "male factor" to this disease; husbands of cervical cancer patients report considerably more sexual partners than husbands of unaffected women (Brinton et al., 1989b; Buckley et al., 1981). Despite early speculation regarding potential effects, more recent studies do not confirm a role for circumcision status of the male partner. Frequency of sexual intercourse with the same male partner also appears unrelated to risk. Recently, intense interest has focused on the role of the human papillomaviruses (HPV), which cause genital warts in both men and women (Koutsky et al., 1988). Abundant laboratory and clinical data support a role for HPV in the etiology of cervical cancer, but it is unlikely that the virus is a necessary and sufficient cause (Schiffman et al., 1993). The role of possible cofactors, including the herpesviruses, hormonal and dietary factors, and smoking, is also being investigated. In a number of studies, cigarette smoking has been found to increase the risk of cervical cancer, especially among long-term or high-intensity smokers (Winkelstein, 1990). Smoking constituents have been found in cervical mucus, but the biologic mechanisms underlying the smoking-cervical cancer relationship have not been identified. Choice of contraceptive method also appears to affect the risk of cervical cancer. Barrier mechanisms lower the risks--probably by decreasing exposure to infectious agents. The reasons for the increased risk associated with oral contraceptives--especially in long-term use--may be more complex. Although there has been concern that the link may merely reflect the correlation of this method with more intensive sexual activity, a number of studies have shown that the excess risk persists after adjustment for a variety of socioeconomic and sexual factors (Brinton, 1991). The role of hormonal factors in the etiology of cervical cancer has been underscored by recent studies which identify multiple births as independent risk factors (Brinton et al., 1989a; Parazzini et al., 1989). There is increasing evidence that nutritional factors may play a role in cervical disease. Several studies suggest that low intake of either vitamin C or beta carotene may be associated with elevations in risk (Brock et al., 1988; Slattery et al., 1990), although this has not always been found (Ziegler et al., 1990). Deficiency in folacin (one of the B complex vitamins) has also been proposed as a risk factor, especially among oral contraceptive users whose stores of this vitamin are depleted. |
* From the Environmental Epidemiology Branch, Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland
