Family Planning Association of Kenya

Where treatment is available, cervical cancer screening can benefit all women. This Kenyan poster invites women for cervical screening.

Relative risks of pre-invasive lesions were for the most part less than 2.0—for example, 1.3 for ever-use (546), 1.4 for past users (169), and 1.8 for low-grade lesions (323). A Swedish study found current use of OCs to be associated with a fourfold increase in risk of pre-invasive lesions overall; risk increased with duration of use (547). One recent study, however, found no association between OC use and pre-invasive lesions (80). For women who had used OCs for five years or more, several recent studies report about a doubling of risk compared with women not using the pill (46, 47, 245, 546). Studies that have looked at various grades of pre-invasive lesions, however, have reported inconsistent findings (46, 251, 323).

Epidemiologic findings on invasive cancer. As with pre- invasive lesions, most studies in the past decade have found that long-term OC use is associated with a slight increase in risk of invasive cervical cancer (304). In many of these studies risk increased with duration of use (43). An analysis of 14 studies found relative risks of invasive cervical cancer to be 1.37, 1.60, and 1.77 for 4, 8, and 12 years of OC use (410).

Some evidence suggests that OCs accelerate the progression of precancerous lesions to invasive cancers. Any increased risk may be concentrated in current and recent users (26, 344). One study found that no increased risk persisted beyond 10 years after OC use ended (344). Another study found that OCs increased the risk of invasive cancer only when first used at a young age, especially at age 17 or younger, a crucial time in the development of a woman's reproductive tract (101).

Interpreting the findings. A number of biological mechanisms have been proposed to explain an association between OCs and cervical neoplasia. Currently, no firm evidence favors any one of these mechanisms. It has been suggested that OCs might: (1) promote the growth of existing lesions, (2) change cervical mucus to increase tissue susceptibility to HPV (491), (3) alter immune response to increase susceptibility to HPV, (4) produce a folate deficiency in the cervix that could stimulate development of abnormal lesions (144, 408), and/or (5) enhance genetic replication of HPV (43, 161, 183, 216, 350, 426).

Observed associations between cervical neoplasia and OCs may reflect the difficulties of studying the issue rather than causal relationships. First, OC use may be part of larger behavior patterns that also increase the risk of cervical cancer (430). Second, cervical neoplasia may be more easily detected in OC users than in other women (detection bias). These difficulties are hard to overcome completely. Furthermore, the biological factors that influence the development of cervical cancer are complex.

Behavioral factors. Studies of cervical cancer and OCs may need to take account of both sexual behavior and smoking. Sexual behavior, particularly age of first intercourse, lifetime number of sexual partners, and use of barrier contraception, are known to affect the risk of developing cervical cancer. Younger age at first intercourse and more partners raise risks. Condom use lowers risks. If women choose OCs because they start sexual activity early or have many sex partners, and they do not use condoms, studies would find a noncausal association between OC use and cervical cancer (64).

There is fairly strong evidence associating cervical cancer and cigarette smoking (523, 527). Several studies suggest about a twofold increase in risk for smokers compared with nonsmokers (46, 102, 168, 547). A Danish study suggested that OC users who smoke are at particularly high risk of cervical cancer. Among women using OCs for six years or more, smokers had a relative risk of 6.0 compared with 2.2 among nonsmokers (245).

J. Doug Story for JHU/CCP

This rimary health cetner in Nepal displays a wall painting near the entrance that promotes oral contraceptives. In many clinics worldwide, health care providers help clients choose the contraceptive method that best suits their individual needs.

Biological factors. Cervical cancer develops slowly. Invasive cancer apparently occurs at the end of a slow progression of pre-invasive lesions. But most mild, and many moderate, pre-invasive lesions regress spontaneously (93, 206). Very few progress to invasive cancer (321, 383). Risk factors for progression at each stage—and for progression to invasive cancer—may vary (44). Hypothetically, OC use could have an independent effect or act as a cofactor at any stage. Thus a causal link between OC use and pre-invasive lesions—if established—would not necessarily imply a link to invasive cancer (184, 346). Research needs to explore why some pre-invasive lesions progress while most regress, and what role, if any, OCs play in progression.

Because HPV is the primary cause of cervical cancer (see sidebar, Preventing Cervical Cancer), researchers have looked for a connection between OCs and the risk of acquiring HPV infection. Findings are mixed. Some studies have reported that OC users are significantly more likely to acquire or have an HPV infection (159, 271, 283, 323, 395, 459, 487). Others have not (24, 51, 198, 233, 279, 367, 426, 449, 489). Studies have not consistently controlled for sexual behavior, however.

HPV targets cervical cells that are actively dividing (244). OCs increase cervical ectopy—the extension of sensitive columnar epithelial cells from the cervical canal to the vaginal surface of the cervix. Thus it is possible that OCs could enhance susceptibility of the cervix to HPV infection (216).