Do cutaneous human papillomavirus genotypes affect head and neck cancer? Evidence and bias-correction from a case-control study.

BACKGROUND:Three genera of human papillomavirus (HPV) infect the oral cavity and oropharynx- alpha (α), beta (β) and gamma (γ). While α-HPV infection is an established risk factor for head and neck cancers (HNC), the role of other genera remains unclear. We aimed to estimate the effect of α-, β-, γ-HPV on HNC using a hospital-based case-control study. METHODS:We recruited incident HNC cases (396) and controls (439), frequency-matched by age and sex from four main referral hospitals in Montreal, Canada. We collected information on sociodemographic and behavior characteristics using in-person interviews, and tested rinse, brush and tumor specimens for HPV genotypes. We estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the effect of HPV on HNC using logistic regression, adjusting for confounding. We conducted probabilistic bias analysis to account for potential exposure misclassification, selection bias, and residual confounding. RESULTS:α-HPV genus had a strong effect on HNC, particularly HPV16 (aOR=22.6; 95% CI: 10.8, 47.2). β-HPV was more common among controls (aOR=0.80; 95% 0.57, 1.11). After adjustment for HPV16, we found weaker evidence for γ-HPV (aOR= 1.29; 95% CI: 0.80, 2.08). Combined bias analyses for HPV16 increased the strength of the point estimate, but added imprecision (aOR=54.2, 95% CI: 10.7, 385.9). CONCLUSIONS:α-HPV, especially HPV16, appears to increase the risk for HNC, while there is little evidence for an effect of β- or γ-HPV. β-HPV may have a preventive effect, while γ-HPV may increase the risk of HNC, although to a lesser extent than that of α-HPV. Results for cutaneous HPV were imprecise and less conclusive. Due to possible epidemiologic biases, the true relation between HPV and HNC could be underestimated in the literature. Further improvement in current methods and more studies of the biologic mechanisms of the three genera in HNC development are warranted.