Angela L Mazul1, Nidia Rodriguez-Ormaza2, James M Taylor3, Dipan D Desai3, Paul Brennan4, Devasena Anantharaman4, Tarik Gheit4, Massimo Tommasino4, Behnoush Abedi-Ardekani4, Andrew F Olshan5, Jose P Zevallos6. 1. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. Electronic address: amazul@unc.edu. 2. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. 3. Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, United States. 4. International Agency for Research on Cancer (IARC), Lyon, France. 5. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. 6. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, United States; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Abstract
OBJECTIVES: Recent 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 METHODS: We 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. RESULTS: Cases 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). CONCLUSIONS: This 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.
OBJECTIVES: Recent 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 p16tumor suppressor protein. MATERIAL AND METHODS: We 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. RESULTS: Cases 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). CONCLUSIONS: This 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.
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