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Background  Both  microRNAs  and human papillomavirus (HPV) infection play an important role in the development and progression of oral squamous cell carcinoma (OSCC). In addition,  microRNAs  affect all facets of the immune/inflammation responses to infection, which may control HPV clearance. We thus hypothesized that  microRNA  polymorphisms modify the association between HPV16 seropositivity and OSCC risk.    Methods  Four single-nucleotide polymorphisms in  microRNAs  were genotyped and HPV16 serology was determined in 325 cases and 335 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariable logistic regression models.    Results  Overall, each polymorphism had no significant main effect on OSCC risk. Compared with the risk among individuals with both  miR146  rs2910164 GG genotype and HPV16 seronegativity, risk of OSCC was increased among those with CG or CC genotype and HPV16 seronegativity (OR, 1.2; 95% CI, 0.9–1.8), GG genotype and HPV16 seropositivity (OR, 3.0; 95% CI, 1.8–5.0), and CG or CC genotype and HPV16 seropositivity (OR, 4.7; 95% CI, 2.3–9.4). Similar results were found for  miR149  rs2292832,  miR196  rs11614913, and  miR499  rs3746444. Analyses stratified by tumor sites and smoking status showed that each polymorphism significantly increased the risk of HPV16-associated squamous cell carcinoma of the oropharynx (SCCOP), and such effect modification was particularly prominent in never smokers.    Conclusions  Our results indicate that  microRNA  polymorphisms modify the risk of OSCC associated with HPV16 seropositivity, particularly in patients with SCCOP and never smokers. Larger studies are needed to verify our findings.

MicroRNA Variants Increase the Risk of HPV-Associated Squamous Cell Carcinoma of the Oropharynx in Never Smokers