Graduation Year

2016

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Epidemiology and Biostatistics

Major Professor

Yangxin Huang, Ph.D.

Co-Major Professor

Anna Giuliano, Ph.D.

Committee Member

Amy Borenstein, Ph.D.

Committee Member

Dana Rollison, Ph.D.

Keywords

Human papillomavirus, HPV, Incidence, anti-HPV antibodies, Recurrence, Sequential genital-anal infections, HIM study

Abstract

Objectives: The aims of this study were to: 1) Assess whether naturally induced anti-HPV antibodies are associated with subsequent acquisition of genital HPV 6, 11, 16, and 18 infections in men, 2) assess the recurrence (redetection) of genital HPV infections of the 9-valent vaccine HPV types and investigate factors associated with recurrent infections among men, and 3) assess the risk of type-specific sequential acquisition of anal HPV infection following a genital HPV infection of the 9-valent vaccine HPV types among men who have sex with women (MSW).

Methods: 4,123 healthy men were followed every six months (median follow-up time 4.1 years). HPV antibodies were measured at baseline using a virus-like particle-based ELISA assay. Genital and anal HPV genotypes were detected using the Roche Linear Array assays. Kaplan-Meier curves and Cox models were developed to assess associations between serum anti-HPV antibody and subsequent incident HPV infections. Individual type analyses and grouped analyses were carried out to assess type-specific recurrence of the 9-valent vaccine HPV types. Risk of sequential anal HPV infection was assessed by examining incident rate ratios (IRR) and adjusted hazard ratios (aHR) among men with a prior genital HPV infection compared to men without a prior genital HPV infection.

Results: 1) Significantly higher rates of incident infections were observed for HPV 16 among baseline HPV 16 seropositive men (aHR 1.37, 95% CI 1.01-1.86). Risk of persistent HPV 18 infection was significantly lower among HPV 18 seropositive men in unadjusted models, but not in the adjusted model, while incident and six-month persistent HPV 6 and 11 infections did not differ by baseline serostatus. 2) Up to 31% of prior prevalent and 20% of prior incident HPV infections recurred over time in individual type analyses. New female sexual partners, frequency of sexual intercourse with female partners, and new male sexual partners were associated with type-specific recurrence of HPV infections (HPV 6, 16, 31 and 58). In grouped analyses, lifetime number of male sexual partners (aOR = 2.40, 95% CI 1.19-4.84) and number of new male sexual partners (aOR 2.35, 95% CI 1.16-4.74) were associated with recurrence of HPV infections. 3) In individual type analyses, men with a prior HPV 16 genital infection had a significantly higher risk of subsequent anal HPV 16 infection (aHR=4.63, 95% CI 1.41-15.23). Significantly higher HRs were observed for any of the nine HPV types (aHR= 2.8, 95% CI1.32-5.99), high risk HPV types (aHR=2.65, 95% CI 1.26, 5.55) and low risk HPV types (aHR=5.89, 95% CI1.29, 27.01) in grouped analyses.

Conclusion: Baseline seropositive status among men was not associated with a reduction in subsequent incident genital HPV 6, 11, and 16 infections, but with a possible protective effect for persistent HPV 18 infections. Men are also susceptible to recurrence of type-specific genital HPV infections, and recurrence of HPV infection was associated with high-risk sexual behaviors. MSW men with prior genital HPV infections are more likely to have a subsequent type-specific anal HPV infection than men who did not have prior genital HPV infections. Understanding the natural history of HPV infections among men is essential to control HPV associated diseases in both men and women.

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