Viral load and short‐term natural history of type‐specific oncogenic human papillomavirus infections in a high‐risk cohort of midadult women

Oncogenic human papillomavirus (HPV) viral load may inform the origin of newly detected infections and characterize oncogenic HPV natural history in midadult women. From 2007 to 2011, we enrolled 521 25–65‐year‐old‐female online daters and followed them triannually with mailed health and sexual behavior questionnaires and kits for self‐sampling for PCR‐based HPV DNA testing. Samples from oncogenic HPV positive women were selected for type‐specific DNA load testing by real‐time PCR with adjustment for cellularity. Linear or logistic regression models were used to evaluate relationships between viral levels, health and sexual behavior, and longitudinal oncogenic HPV detection. Type‐specific viral levels were borderline significantly higher in oncogenic HPV infections that were prevalent versus newly detected (p = 0.092), but levels in newly detected infections were higher than in infections redetected after intercurrent negativity (p < 0.001). Recent sex partners were not significantly associated with viral levels. Compared with prevalent infections detected intermittently, the likelihood of persistent (OR = 4.31, 95% CI: 2.20–8.45) or single‐time (OR = 1.32, 95% CI: 1.03–1.71) detection increased per 1‐unit increase in baseline log10 viral load. Viral load differences between redetected and newly detected infections suggest a portion of new detections were due to new acquisition, although report of recent new sex partners (a potential marker of new infection) was not predictive of viral load; oncogenic HPV infections in midadult women with new partners likely represent a mix of new acquisition and reactivation or intermittent detection of previous infection. Intermittent detection was characterized by low viral levels, suggesting that intermittent detection of persisting oncogenic HPV infection may be of limited clinical significance. What's new? Infection with HPV can lead to cancer, and women often acquire these infections in early adulthood. When they are detected in older adults, is it possible to discern whether the infection is newly acquired or simply a recent flare‐up of a previous infection? This study looked at whether viral load data could predict infection status. The authors measured HPV viral loads in women ages 25‐65 and correlated the levels from newly detected, prevalent, and intermittent HPV infections with other measures of health and sexual behavior. Viral levels appeared higher in prevalent infections than in those newly acquired, and t