Risk factors for acquisition and clearance of oral human papillomavirus infection among HIV-infected and HIV-uninfected adults

Abstract

Human papillomavirus (HPV) causes the majority of oropharyngeal cancers in the United States, yet the risk factors for and natural history of oral HPV infection are largely unknown. In 2010-2011, a US-based longitudinal cohort study of 761 human immunodeficiency virus (HIV)-infected and 469 at-risk HIV-uninfected participants from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study was initiated. Semiannually collected oral rinses were evaluated for 37 HPV genotypes using the Roche LINEAR ARRAY HPV Genotyping Test (Roche Molecular Systems, Pleasanton, California), and factors associated with oral HPV incidence and clearance were explored using adjusted Wei-Lin-Weissfeld modeling. Through 2013, the 2-year cumulative incidence of any type of oral HPV infection was 34% in HIV-infected persons and 19% in HIV-uninfected persons. However, many of these infections cleared. Seven percent of incident infections and 35% of prevalent infections persisted for at least 2 years. After adjustment for other risk factors, HIV infection (adjusted hazard ratio = 2.3, 95% confidence interval: 1.7, 3.2), reduced current CD4 cell count, and increased numbers of oral sex and "rimming" partners increased the risk of incident oral HPV infection, whereas male sex, older age, and current smoking increased the risk of oral HPV persistence (each P < 0.05). This helps explain the consistent associations observed between these factors and prevalent oral HPV infection in previous cross-sectional studies.

Keywords: HIV; head and neck cancer; human papillomavirus; natural history; oral HPV; risk factors.

Figure 1.

Cumulative incidence of any oral human papillomavirus (HPV) infection by human immunodeficiency virus (HIV) status and current CD4 cell count (cells/µL) in the Persistent Oral Papillomavirus Study, 2010–2013. This cumulative-incidence graph represents the percentage of participants with at least 1 incident oral HPV infection detected during the follow-up period. All persons in CD4 cell count categories were HIV-infected. Participants were considered to have an incident oral HPV infection if they tested positive for a type-specific oral HPV infection that they had tested negative for at the baseline visit. When HIV status/CD4 cell count was utilized as a categorical variable, the P value for trend was less than 0.001. This graph presents the linear trend in oral HPV incidence in these groups as derived using Wei-Lin-Weissfeld modeling.

Figure 2.

Clearance of incident (parts A and C) and prevalent (parts B and D) oral human papillomavirus (HPV) infection among human immunodeficiency virus (HIV)-infected and HIV-uninfected persons in the Persistent Oral Papillomavirus Study, 2010–2013. Parts A and B show results obtained when a single negative test was required for the definition of clearance; parts C and D show results obtained when 2 consecutive negative tests were required for an infection to be considered cleared. Numbers of persistent and total infections at 12 months were A) 92/464, B) 221/625, C) 121/461, and D) 363/589. When rates of oral HPV clearance in HIV-infected persons and HIV-uninfected persons were compared using unadjusted Wei-Lin-Weissfeld modeling, the hazard ratios were A) 0.96 (95% confidence interval (CI): 0.70, 1.3), B) 0.94 (95% CI: 0.72, 1.2), C) 0.68 (95% CI: 0.49, 0.95), and D) 0.85 (95% CI: 0.62, 1.2).