Association of genetic variants with tumor HPV16 status and survival in squamous cell carcinoma of the oropharynx

• Genetic variants interact with HPV E7 and E6 to affect their biological function.
• Genetic variants significantly predict HPV-positive SCCOP tumors.
• Genetic variants significantly predict survival of HPV-positive SCCOP patients.
• Genetic variants have significant implications for treatment modalities & prevention.

SummaryObjectivesGenetic polymorphisms of genes in cell cycle, apoptosis, and inflammation/immune response pathways may control the mechanisms of HPV clearance and HPV escape of immune surveillance and thus may affect both tumor HPV16 status and possibly related outcomes of squamous cell carcinoma of the oropharynx (SCCOP) patients.Materials and MethodsWe determined tumor HPV16 status and genotyped selected polymorphisms in key genes involved in cell cycle, apoptosis, and inflammation/immune response pathways in 401 incident SCCOP patients. Unconditional logistic regression models, Kaplan–Meier analysis, and Cox proportional hazards regression were used to evaluate associations and survival.ResultsCompared to the corresponding common homozygous genotypes, the variant genotypes of genes in cell cycle (p53, p73, MDM2, p16), apoptosis (CASP8, and Fas), and inflammation/immune response pathways (IL1β and IL10) were significantly associated with HPV16-positive tumors among SCCOP patients. In HPV16-positive SCCOP patients only, compared to those with the corresponding common homozygous genotypes, patients with variant genotypes of p53 (119G > C), MDM2 (309T > G), p16 (580C > T), Fas (1377G > A), and IL1β (14T > C) had significantly better overall survival, and approximately 40–70% reduced or 5-fold increased risk of overall death, respectively, after adjustment for important prognostic confounders. Moreover, the combined adverse genotypes of 5 variants were also significantly associated with reduced risk of overall death of HPV16-positive SCCOP.ConclusionThese results suggest that genetic polymorphisms in likely functional regions of the genes in these pathways may individually or, more likely, jointly affect individual susceptibility to HPV16 tumor status and constitute the confounding effect on HPV16-related clinical outcomes. Validation of our findings is warranted.