Cervical Cancer There may be a weak association between OC use and cancer of the cervix. A systematic review of 28 epidemiologic studies of cervical cancer in OC users compared with those who never used OCs reported summary relative risks of 1.1 (95% CI, 1.1–1.2) at less than 5 years of pill use, 1.6 (1.4–1.7) at 5 to 9 years, and 2.2 (1.9–2.4) at 10 or more years (166). A 2007 update by these same authors reported a pooled relative risk for all studies of 1.9 (95% CI, 1.69–2.13) for invasive cervical cancer or CIN3/carcinoma in situ (CIS) with 5 or more years of OC use. Risk declined after use ceased and by 10 years returned to that of never users. Too few had used progestin-only pills to provide a conclusion as to their effect. For injectable progestins, the relative risk was very slightly increased to 1.22 (95% CI, 1.01– 1.46), which was just statistically significant (167). Critics of these studies argued that causation is not proven because few adequately control for the key behavioral factors of partners, use of barrier contraception, and adequacy of cervical cancer screening (168). Important risk factors for cervical cancer are early sexual intercourse and exposure to HPV. Women who used OCs typically started sexual relations at younger ages than women who have not used OCs and, in some studies, report having had more partners. These factors increase one’s chance of acquiring HPV, the most important risk factor for cervical cancer. Because barrier contraceptives reduce the risk of cervical cancer, use of alternative choices for contraception compounds the difficulty in establishing an association with OC use alone (169). The presence of HPV types 16 or 18 is associated with a 50-fold increase in risk for preneoplastic lesions of the cervix (170). Adenocarcinomas of the cervix are rare, they are not as easily detected as other lesions by screening cervical cytology, and the incidence appears to be increasing. One study found a doubling of risk for adenocarcinoma with OC use that increased with duration of use, reaching a relative risk of 4.4 if total use of OCs exceeded 12 years (171). The results of this study were adjusted for history of genital warts, number of sexual partners, and age at first intercourse. Another summary of case-control studies that includes testing for HPV. HPV types 16 or 18 were present in 82% of the patients, yielding a relative risk of 81.3 (95% CI, 42.0–157.1) for the disease. Cofactors identified with adenocarcinoma included longer-term use of hormonal contraception. Intrauterine device use was associated with reduced relative risk of 0.41 (95% CI, 0.18–0.93) (172). Use of hormonal contraception by women from aged 20 to 30 years is estimated to increase the incidence of cervix cancer (any cervix cancer, or CIN3/CIS) diagnosed by age 50 from 7.3 to 8.3 per 1,000 women in lesser-developed countries and from 3.8 to 4.5 in developed countries (172). Use of OCs is, at most, a minor factor in causation of cervical cancer; these findings emphasize the need to immunize against HPV and to provide cervical cancer screening worldwide. To reduce risk, women who are not in mutually monogamous relationships should be advised to use barrier methods in addition to hormonal contraception.