Proportion of new genital human papillomavirus detections attributable to latent infections: Implications for cervical cancer screening

Background: Infections with human papillomaviruses (HPV) may enter into a latent state in epithelial basal cells, and eventually become reactivated following loss of immune control. It is unclear what proportion of incident detections of HPV are due to reactivation of previous latent infections versus new transmissions. Methods: The HITCH cohort study prospectively followed young newly formed heterosexual partners recruited between 2005-2011 in Montreal, Canada. We calculated the fraction of incident HPV detections non-attributable to sexual transmission risk factors with a Bayesian Markov state transition model. Results are the median (2.5-95.5th percentiles) of the estimated posterior distribution. Findings: 544 type-specific incident HPV detection events occurred in 849 participants; 32.5% of all incident HPV detections occurred in participants whose HITCH partners were negative for that HPV type and who did not report having sex with anyone else over follow-up. We estimate that 42.7% (38.4-47.2%) of all incident HPV detections in this population might be attributable to reactivation of latent infections, not transmission. Interpretation: A positive HPV test result in many cases may be a reactivated past infection, rather than a new infection from recent sexual behaviors or partner infidelity. The potential for reactivation of latent infections in previously HPV-negative women should be considered in the context of cervical cancer screening.