Short-term natural history of high-risk human papillomavirus infection in mid-adult women sampled monthly

Abstract

Characterizing short-term HPV detection patterns and viral load may inform HPV natural history in mid-adult women. From 2011-2012, we recruited women aged 30-50 years. Women submitted monthly self-collected vaginal samples for high-risk HPV DNA testing for 6 months. Positive samples were tested for type-specific HPV DNA load by real-time PCR. HPV type-adjusted linear and Poisson regression assessed factors associated with (i) viral load at initial HPV detection and (ii) repeat type-specific HPV detection. One-hundred thirty-nine women (36% of 387 women with ≥4 samples) contributed 243 type-specific HR HPV infections during the study; 54% of infections were prevalent and 46% were incident. Incident (vs. prevalent) detection and past pregnancy were associated with lower viral load, whereas current smoking was associated with higher viral load. In multivariate analysis, current smoking was associated with a 40% (95% CI: 5-87%) increase in the proportion of samples that were repeatedly positive for the same HPV type, whereas incident (vs. prevalent) detection status and past pregnancy were each associated with a reduction in the proportion of samples repeatedly positive (55%, 95% CI: 38-67% and 26%, 95% CI: 10-39%, respectively). In a separate multivariate model, each log10 increase in viral load was associated with a 10% (95% CI: 4-16%) increase in the proportion of samples repeatedly positive. Factors associated with repeat HPV detection were similar to those observed in longer-term studies, suggesting that short-term repeat detection may relate to long-term persistence. The negative associations between incident HPV detection and both viral load and repeat detection suggest that reactivation or intermittent persistence was more common than new acquisition.

Keywords: human papillomavirus; natural history; viral load; women.

Figure 1

Enrollment and follow-up status of mid-adult women in Seattle, WA (2011–2012)

Figure 2. Type-specific HR HPV positivity over time among mid-adult women in Seattle, WA (2011 – 2012)

Data are presented separately for prevalent (n=132) and incident (n=111) infections. The x-axis denotes the sample window. In this figure, sample window 0 denotes the initial type-specific positive sample; for prevalent infections, this is always the baseline sample, whereas for incident infections, this is always a subsequent sample. Sample windows 1 through 6 are numbered in relation to the first type-specific positive sample (e.g., sample window 1 denotes the first sample collected after the initial positive, sample window 2 denotes the second sample collected after the initial positive, etc). The y-axis denotes the proportion of samples positive for the specific HR HPV type at the given sample window, and the error bars represent 95% confidence intervals for each estimate (excluding sample window 0). For example, a prevalent infection with the pattern (+ − + − + + −) would contribute to the prevalent denominator at all sample windows, and to the numerator at windows 0, 2, 4, and 5; an incident infection with the pattern (− − − + − + +) would contribute to the incident denominator at sample windows 0, 1, 2, and 3 only, and to the numerator at windows 0, 2, and 3. The table depicts the numerators (n) and denominators (N) at each sample window for incident and prevalent infections. This figure includes HPV infections with 19 HR types (HPV-16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82 and IS39).