Incidence and duration of type-specific human papillomavirus infection in high-risk HPV-naïve women: results from the control arm of a phase II HPV-16/18 vaccine trial

Abstract

Objectives: Persistence of human papillomaviruses (HPVs) is necessary for cervical carcinogenesis. We evaluated incidence and duration of type-specific HPV infections and the influence of age and number of sexual partners.

Methods: Data were obtained from 553 women (15-25 years), who were seronegative and DNA-negative for high-risk HPV (HR-HPV) types and were enrolled in the placebo arm of a randomised trial of the HPV-16/18 vaccine (NCT00689741/NCT00120848). They were followed for 6.3 years. Cervicovaginal samples were self-collected at 3-month intervals for up to 27 months, and cervical samples were collected by clinicians at 6-month intervals until study end. Samples were tested for HPV types using a broad-spectrum PCR assay. Incidence rate ratios (RRs) and 95% CIs were used to estimate the association among age, sexual habits and HPV acquisition.

Results: Incidence rates (95% CI) using cervical samples were 11.8 (10.4 to 13.4) and 5.6 (4.7 to 6.6) per 1000 women-months for HR-HPVs and low-risk HPVs (LR-HPVs), respectively. Equivalent rates in combined cervicovaginal and cervical samples were 17.2 (15.4 to 19.2) and 6.9 (5.9 to 8.0), respectively. 54 per cent of HR-HPV types from combined cervicovaginal and cervical samples persisted for 1 year compared with 32.3% for LR-HPV types. The risk of acquiring any HPV infection was higher among women aged <21 years (RR=1.33, 95% CI 1.1 to 1.7) and women having >1 sexual partner (RR=1.83, 95% CI 1.4 to 2.4) at baseline.

Conclusions: HR-HPV infections were more common and lasted longer on average than LR-HPV infections. HPV acquisition was more common in younger women with multiple sexual partners.

Trial registration number: NCT00689741, NCT00120848; Post-results.

Keywords: Cervical cancer; Cohort study; EPIDEMIOLOGY; Human papillomavirus; Natural history.

Figure 1

Cumulative probability of persistent detection of the first episode of HPV infection (as per liberal definition) over time stratified by age (upper graphs A, B, C; solid line <21 years and dashed line ≥21 years) and sexual partners (lower graphs D, E, F; solid line ≥2 partners, dashed line 0/1 partner). Log-rank test p values; A=0.0806, B=0.1276, C=0.9338, D=0.3436, E=0.4601, F=0.2186. (A and D) Any HPV type; (B, E) HR-HPV; and (C and F) LR-HPV. The Y-axis represents the probability that HPV infections remain detectable. Clearance of an infection episode as per the liberal definition (see text for details); combined cervical and cervicovaginal samples. HPV, human papillomavirus; HR-HPV, high-risk HPV; LR-HPV, low-risk HPV.

Figure 2

Cumulative probability of detecting an HPV infection over time stratified by the age group (upper graphs A, B, C; solid line <21 years and dashed line ≥21 years) and number of sexual partners (lower graphs D, E, F; solid line ≥2 partners and dashed line 0/1 partner). Log-rank test p values; A=0.0099, B<0.0001, C=0.122, D<0.0001, E=0.0007, F=0.2712. (A and D) Any HPV type; (B and E), HR-HPV; and (C and F) LR-HPV. The Y-axis represents cumulative proportion of infections detected. Combined cervical and cervicovaginal samples. HPV, human papillomavirus; HR-HPV, high-risk HPV; LR-HPV, low-risk HPV.