Prognostic significance of non-HPV16 genotypes in oropharyngeal squamous cell carcinoma

• First to study the prognostic significance of non-HPV16 genotypes with p16 status.
• HPV16-positve oropharynx tumors have better survival than non-HPV16-positive genotypes.
• The survival benefit for HPV16-positve genotypes holds for tumors positive for p16, but not for p16-negative tumors.

ObjectivesRecent studies have found that cases with oropharyngeal squamous cell carcinoma (OPSCC) positive for HPV16 genotype have better overall survival compared with cases positive for other HPV genotypes. We sought to further replicate these studies and determine if this relationship is modified by expression of p16 tumor suppressor protein.Material and methodsWe identified 238 OPSCC cases from the Carolina Head and Neck Cancer Study (CHANCE) study, a population based case-control study. Tumors that tested positive solely for HPV16 genotype and no other genotypes with PCR were classified as HPV16-positive. Tumors positive for any other high-risk HPV genotype were classified as non-HPV16-positive. Expression of p16 in the tumor was determined with immunohistochemistry. Follow-up time was calculated from the date of diagnosis to date of death or December 31, 2013. Overall survival was compared with the Kaplan-Meier curves and log-rank test. Hazard ratios (HR) adjusted for smoking, alcohol use, sex, race, and age was calculated with the Cox proportional hazard regression.ResultsCases with HPV16-positive OPSCC had better overall survival than cases with non-HPV16-positive OPSCC (log-rank p-value: 0.010). When restricted to OPSCC cases positive for p16 expression, the same trend continued (log-rank p-value: 0.002). In the adjusted model, cases with non-HPV16-positive OPSCC had greater risk of death compared to cases with HPV16-positive tumors (HR: 1.92; 95% CI: 1.03, 3.60).ConclusionsThis finding indicates that HPV genotyping carries valuable prognostic significance in addition to p16 status and future survival studies of OPSCC should take into account differing HPV genotypes.