Cytokine variants predict outcome of squamous cell carcinoma of the oropharynx

Genetic variants of genes in inflammation/immune response pathways may control the mechanisms of HPV clearance and HPV escape of immune surveillance and thus may affect both tumor HPV status and possibly related outcomes of squamous cell carcinoma of the oropharynx (SCCOP) patients. We determined tumor HPV16 status and genotyped selected polymorphisms in key genes involved in inflammation/immune response pathways in 401 incident SCCOP patients. Logistic regression models, Kaplan-Meier analysis, and Cox proportional hazards regression were used to evaluate associations and survival. Compared to the patients with the corresponding variant or common homozygous genotypes, the patients with the common homozygous genotypes of IL1β orvariant genotypes of IL10 in inflammation/immune response pathway had significantly 3.3-6.0 times likely to be HPV16-positive tumors among SCCOP patients, respectively. Furthermore, the patients with 4-5 combined risk genotypes of 5 polymorphisms exhibited a significantly greater association with HPV16-positive tumor status (OR, 12.4, 95% CI, 4.1-24.3), and the association is in a statistically significant dose-effect relationship (P<0.001). In HPV16-positive SCCOP patients only, the combined unfavorable genotypes of 5 cytokine variants were also significantly associated with increased risk of overall death after adjustment for important prognostic confounders and the association is in a statistically significant dose-effect relationship (P<0.001). These results suggest that genetic polymorphisms in cytokine genes may individually or, more likely, jointly affect individual susceptibility to HPV tumor status and constitute the confounding effect on HPV-related clinical outcomes. Validation of our findings is needed.