MDM4 genetic variants predict HPV16-positive tumors of patients with squamous cell carcinoma of the oropharynx

The increasing incidence of squamous cell carcinoma of the oropharynx (SCCOP) is majorly attributed to the human papillomavirus (HPV) infection. Both HPV and MDM4 play a critical role in inhibition of p53 activity, thus affecting HPV tumor status of SCCOP. Three polymorphisms in MDM4 were genotyped from blood genomic DNA samples and HPV16 status in tumor specimens was examined. Odds ratio (OR) and 95% confidence intervals (CIs) in univariate and multivariable logistic regression models were calculated for the associations between these polymorphisms and HPV16 status. Three MDM4 variant genotypes were significantly associated with HPV16 tumor status among SCCOP patients compared with the common homozygous genotypes (OR, 0.6; 95% CI, 0.4-1.0 for rs10900598; OR, 1.6, 95% CI; 1.1-2.4 for rs1380576; and OR, 1.8, 95% CI, 1.1-2.9 for rs11801299; respectively). When we combined all risk genotypes of the 3 polymorphisms, the patients carrying 1-3 MDM4 risk genotypes were approximately 2.5 time as likely to have an HPV16-positive tumor than those with no risk genotypes (OR, 2.5, 95% CI, 1.6-3.9). Additionally, modifying effect of MDM4 risk genotypes was more pronounced among non-Hispanic white, neversmokers, and never-drinkers. Potential functional polymorphisms in MDM4 may serve as biomarkers for predicting tumor HPV16 status among SCCOP patients, particularly in non-Hispanic white, never-smokers and never-drinkers. However, validation of these results in larger studies is needed.