The prognosis in SMM is poor, particularly for those with distant metastasis or without surgery. Multimodality treatment may improve survival.

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Background Genetic polymorphisms in the 3′ UTRs targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behavior of individual miRNAs. An insertion (Ins)/deletion (Del) polymorphism (rs3783553) in the 3′ UTR of IL-1α may disrupt a binding site for miRNA-122. IL-1α plays an important role in inflammation, immunity, and defense against infection. Thus, we hypothesized that the rs3783553 polymorphism affects individual susceptibility to HPV-associated oral squamous cell carcinoma (OSCC). Methods We genotyped the rs3783553 polymorphism; and determined HPV16 L1 serology, tumor HPV16 DNA, and serum IL-1α expression. Univariate/multivariable logistic regression models were used to calculate associations. Results We found that HPV16 L1 seropositivity alone was associated with an increased risk of OSCC (OR, 3.1; 95% CI, 2.1–4.6), and the risk of HPV16-associated OSCC was modified by the rs3783553 polymorphism. Patients with both HPV16 L1 seropositivity and Del/Del genotype for the rs3783553 had the highest risk of OSCC when using patients with HPV16 L1 seronegativity and Ins/Del + Ins/Ins genotypes as a comparison group. Notably, that effect modification was particularly pronounced in several subgroups (e.g., SCCOP, never-smokers, and never-drinkers). The patients with Del/Del genotype were approximately 3.0 times more likely to have HPV16-positive SCCOP tumors compared to those patients with Ins/Del + Ins/Ins genotypes. Additionally, functional relevance of this variant was characterized to explore the genotype-phenotype correlation. Conclusion These results suggest that IL-1α 3′ UTR rs3783553 polymorphism may be functional and influence susceptibility to HPV16-associated OSCC, particularly for SCCOP. Validation of our findings is warranted.

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