Determinants of Acquisition and Clearance of Human Papillomavirus Infection in Previously Unexposed Young Women

Abstract

Background: Global variation in human papillomavirus (HPV) prevalence and persistence may be explained by differences in risk factors, such as sexual activity, oral contraceptive use, and behavioral factors. We evaluated determinants of acquisition and clearance of HPV infection among young women previously unexposed to HPV.

Methods: Five hundred thirty-four women aged 15 to 25 years who were cytology and HPV DNA negative, and seronegative for anti-HPV-16/18 antibodies, were recruited (July 2000-September 2001) from study centers in Brazil, the United States, and Canada (NCT00689741/NCT00120848). They were followed up for 76 months. Cervical samples were HPV genotyped via polymerase chain reaction. We used multivariable (forward stepwise, P = 0.15) Cox proportional hazards regression to estimate rate ratios (RR) and 95% confidence intervals (CI), separately according to length of follow-up time.

Results: On short-term follow-up (0-27 months), 257 (48%; 8535.80 person-months; incidence rate = 30.11; 95% CI, 26.64-34.02) incident HPV infections were detected. Marital status, lifetime number of sex partners, history of any sexually transmitted disease, and occasional use of oral contraceptives were strongly associated with acquisition of any HPV. Having 2 or more lifetime sex partners (RR, 2.03; 95% CI, 1.37-3.02) and a history of any sexually transmitted disease (RR, 1.98; 95% CI, 1.19-3.29) were the most important determinants of high-risk HPV (hrHPV) incidence. During the entire follow-up (0-76 months), an increased hrHPV clearance was found among women in North America (RR, 1.38; 95% CI, 1.08-1.78) and black women (RR, 1.64; 95% CI, 1.04-2.60). Greater number of lifetime partners was associated with reduced clearance rates for any HPV (RR, 0.65; 95% CI, 0.43-0.98).

Conclusions: We identified variation in risk of HPV acquisition and clearance among women unexposed to HPV at baseline.

Conflict of interest statement

Conflicts of Interest and Sources of Funding: A.V.R. has received reimbursement from the GSK group of companies for travel expenses, presenting at the International Papillomavirus Conference in 2011 (Berlin) and 2012 (Puerto Rico). P.N., C.M.R.-M., J.C.T., A.-B.M., D.M.H., and S.K.T. have received, either directly or through their institution, research grants from the GSK group of companies to conduct the clinical studies reported here. P.N. has received research grants for other clinical trials sponsored by the GSK group of companies. J.C.T. has received payments from the GSK group of companies for lectures including service on speaker bureau. A.-B.M. and J.C.T. have received payments for participating in advisory board meetings for the GSK group of companies. N.S.dC. has received financial support from the GSK group of companies as clinical investigator for the PATRICIA trial and for lectures. E.L.F. has served as an occasional consultant to companies involved in human papillomavirus (HPV) vaccines (Merck and GSK group of companies) and in HPV diagnostics (Roche, Gen-Probe, BD). His institution has received an unrestricted research grant from Merck. G.D. was employed by the GSK group of companies at the time the study was conducted but is now a full-time employee of Takeda Pharmaceuticals. He holds shares in the GSK group of companies and Takeda Pharmaceuticals, and holds patents in the Human Papillomavirus and in the Herpes Simplex virus vaccine fields. B.R. and P.C.dB. were paid by GSK as part of study. M.E.Z. declares no conflicts of interest. The following studies (NCT00689741 and NCT00120848) were funded by GlaxoSmithKline Biologicals S.A., which also provided support for publication coordination. The McGill University (Quebec, Canada) covered all costs related to statistical analysis and publication development. G.S.K. was not involved in the analysis of data. The authors received no financial support or other form of compensation for the development of the manuscript. G.S.K. had the opportunity to review the manuscript.

Figures

Figure 1

Schematic timeline and specimen collection. Cervicovaginal testing was done at every visit between months 0 and 27 (short-term follow-up), but was optional at month 21 and month 27 (Visits 10 and 12, respectively). Cervical testing was done at every visit between months 40 and 76 (long-term follow-up), but was also done at the screening visit and at month 6, month 12, and month 18 (visits 1, 4, 7, and 9, respectively). Cervicovaginal testing was optional at month 46, month 58, and month 70 (visits 14, 16, and 18, respectively).