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

Abstract

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.

Keywords: epidemiology; human papillomavirus; persistence; viral load; women.

Figure 1

Visual overview of main viral load analyses

Figure 2

Mean log₁₀ type-specific oncogenic HPV viral load per nanogram of cellular DNA over time for a) prevalent and b) incident infections detected intermittently, transiently and persistently for 4, 8 and 12 months. Figures include types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, 82 (type 53 was excluded from all viral load analyses). Only visits with type-specific positive results by the Roche assay are included. For prevalent infections, month 0 is baseline. For incident infections, month 0 is the time of 1^st detection by the Roche assay. Months 4, 8, and 12 are subsequent visits occurring at approximately 4-month intervals. Data points are jittered to prevent overplotting.