October 26, 2010
Women diagnosed with cervical cancer report longer duration and more recent use of combined oral contraceptives (COCs). It is unclear whether COC use is associated with upstream events of human papillomavirus (HPV) infection prior to development of clinical disease. The objective of our study was to assess the association of contraceptive use on the risk for prevalent HPV infection in a cohort of long-term hormonal contraceptive (HC) users. One thousand and seventy (n = 1,070) HIV-negative women aged 20–37 from Thailand enrolled in a prospective study of the natural history of HPV. Baseline HPV genotype information, recency and duration of HC use, sexual behavior, other sexually transmitted infection (STI) information and cervical cytology and histology were assessed. At enrollment, 19.8% and 11.5% of women were infected with any HPV or any high-risk (HR)-HPV, respectively. After adjustment for age, current and past sexual risk behaviors, STI history and cytology, the use of COCs for >6 years was found to be associated with an increased risk of infection with any HPV [prevalence ratio (PR): 1.88 (1.21, 2.90)] and any HR-HPV [PR: 2.68 (1.47, 4.88)] as compared to never users. Recent, long-term COC use was associated with an increased risk for prevalent HPV infection independent of sexual behavior and cervical abnormalities. No similar association was observed for recent or long duration use of progestin-only contraceptives (i.e., depomedroxyprogesterone acetate). These data suggest that COC use may impact early upstream events in the natural history of HPV infection.
Cervical cancer is the second most common cancer among women worldwide and a leading cause of cancer-related mortality in the developing world.1 Genital human papillomavirus (HPV) infections have been identified as a necessary cause of cervical cancer.2–4 More than 35 different types of HPVs infect the genital tract, with ∼18 types considered oncogenic or potentially oncogenic.5, 6 Roughly 291 million women worldwide are currently infected with one of these anogenital HPVs, and approximately 80% of women will be exposed at some point in their lifetime, making HPV the most common sexually transmitted infection (STI).7 However, a majority of HPV infections spontaneously resolve within 1–2 years postdetection. Therefore, other environmental, host and viral cofactors are likely required for the development of cervical cancer.8
Long-term use of combined oral contraceptives (COCs) has been shown in several case–control studies to be associated with cervical cancer diagnosis among HPV-positive women.9–12 However, it is unclear whether this association is driven by COCs’ effect on carcinogenesis or on upstream subclinical endpoints of the natural history such as HPV acquisition and persistence as prospective studies assessing these relationships are inconsistent.13–19 A systematic review of 19 studies looking at COC use and prevalent HPV infection demonstrated an inconsistent association with a high degree of heterogeneity across studies.20 Most of the studies included in this review sampled either young women (<30 years of age) or older women (>35 years of age). Studies that sampled younger women and used highly sensitive PCR-based HPV DNA detection methods were more likely to see an association among current users21 as well as users who reported short-duration (<5 years)22, 23 and medium-duration (5–9 years) users.22, 24 Conversely, studies that addressed the association of COC use and HPV prevalence among women >35 years who were selected as age-matched controls in case–control studies assessing the effects of COCs on either cervical carcinoma9 or cervical intraepithelial neoplasia 3 (CIN3)19 showed no association with current, short-, medium- or long-term COC use. The difference in association across studies by age suggests that COCs are exerting their influence on a very narrow window in the HPV natural history either at the point of HPV acquisition or at the point of the establishment of a persistent infection prior to the development of high-grade precancerous lesions or cervical cancer.
To better examine the association of hormonal contraceptive (HC) use on early virologic endpoints, we examined the cross-sectional association of duration and recency of COC use on HPV prevalence in a cohort of 20- to 37-year-old women recruited from family planning clinics in Thailand.