Association of Chlamydia trachomatis Infection With Redetection of Human Papillomavirus After Apparent Clearance

Infections with human papillomaviruses (HPV) are very common in young, sexually active women [1, 2] and many studies have investigated the association of factors, including sexual behaviors and sexually transmitted infections (STIs), that influence HPV-related outcomes. An association of Chlamydia trachomatis genital infections and genital HPV is observed at several points in the development of HPV-associated cervical cancer, including the acquisition of HPV infection [3], duration of HPV persistence [4, 5], and development of cervical cancer [6–8]. An association between C. trachomatis infections and HPV redetection after an interval of viral clearance has not been described. Ninety percent of type-specific HPV becomes undetectable after 12–24 months using standard polymerase chain reaction assays of genital samples and is deemed “cleared” if the HPV type is not detected in 2 or 3 subsequent, consecutive samples [9, 10]. Redetection refers to subsequent identification of a specific HPV type after it has apparently cleared. Such redetection may have occurred due to repeat infection with the same HPV (or variant) type or reemergence of an existing infection that had become undetectable [11]. Given that persistent oncogenic HPV infections are associated with HPV-related cancers, understanding of a role of C. trachomatis infections and other factors in HPV redetection would add to understanding of the pathogenesis of HPV-associated neoplasia as well as support clinical and public health chlamydia control efforts. In this study, a cohort of adolescent women were followed closely for almost 6 years with quarterly testing for HPV and other STIs [12]. HPV infections were common in the cohort, and most HPV types became nondetectable after variable time periods. However, redetection of a specific HPV type after a period of nondetection (approximately >6 months) was observed in a subset of these study participants. There is no consensus whether the loss of HPV reflects HPV clearance or the establishment of latency [13]. There is human data to support that redetection of the same HPV type is explained, in part, by new sexual exposures [14, 15]. However, not all infections were accounted for by a new sex partner in these studies, and alternative explanations need to be assessed. Human data has suggested reactivation of HPV when new HPV types were found in immunosuppressed women who had remained sexually abstinent [16, 17]. Animal models with rabbits have demonstrated HPV viral latency and that these latent infections are virally capable of producing clinical lesions after wounding [18]. It has been suggested that the basal stem cells can be infected by and contain HPV in very low cell numbers in humans and that processes such as wound repair after an inflammatory event or trauma, hormonal regulation, or loss of immunological surveillance lead to basal cell differentiation and redetection [18, 19]. Therefore, we hypothesized that factors associated with states of inflammation (ie, STIs), immunogenicity, recurrent HPV exposure (lack of condom use, coital activity, number of sexual partners), or hormonal factors (birth control) could possibly be related redetection. This study describes the occurrence and frequency of redetection after periods of nondetection and examines potential factors, biologic and behavioral, associated with type-specific redetection.