Interaction of HPV16 and Cutaneous HPV in Head and Neck Cancer

Abstract

Objectives: Human papillomavirus 16 (HPV16) is an established risk factor for Head and Neck Cancer (HNC). Recent reports have shown that genotypes from the beta (β) and gamma (γ) genera, also known as cutaneous HPV, can be found in the oral cavity, but their role is largely unidentified. We investigated the interaction between oral HPV16 and cutaneous HPV in HNC.

Methods: We use data on incident HNC cases (n = 384) and frequency-matched hospital-based controls (n = 423) from the HeNCe Life study in Montreal, Canada. Participants were tested for alpha HPV and cutaneous genera using oral mouth rinse and brush samples. We used unconditional logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence interval (CI) as a measure of the effect between HPV and HNC and assessed the interaction between HPV genotypes on the multiplicative and additive scales.

Results: Prevalence of HPV infection was higher among cases (73%) than controls (63.4%), with cases more likely to be coinfected with more than a single genotype, 52.9% vs. 43.5%, respectively. Infection with HPV16 alone had a strong effect on HNC risk aOR = 18.2 [6.2, 53.2], while infection with any cutaneous HPV, but not HPV16, appeared to have the opposite effect aOR = 0.8 [0.6, 1.1]. The observed effect of joint exposure to HPV16 and any cutaneous HPV (aOR = 20.4 [8.3, 50.1]) was stronger than the expected effect based on an assumption of independent exposures but was measured with considerable imprecision. While the point estimate suggests a positive interaction between HPV16 and cutaneous HPV, results were imprecise with relative excess risk due to interaction (RERI) = 2.4 [-23.3, 28.2].

Conclusion: There could be biologic interaction between HPV16 and genotypes from cutaneous genera, which warrants further investigation. Although cutaneous HPVs are not usually found in tumor tissues, they are cofactors that could interact with HPV16 in the oral cavity and thus strengthen the latter's carcinogenic effect.

Keywords: HPV; case–control studies; head and neck cancer; human papillomavirus.

Figure 1

Interaction between α-HPV and β-HPV Marginal estimation of probability of HNC. from a logistic model with interaction between α-HPV and β-HPV. High Risk genotypes as identified by IARC: HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. Model is adjusted for age, sex, smoking, and alcohol.

Figure 2

Interaction between α-HPV and γ-HPV. Marginal estimation of probability of HNC from a logistic model with interaction term between α-HPV and γ-HPV. Model is adjusted for age, sex, smoking, and alcohol.