Title: Effect of HPV on head and neck cancer patient survival, by region and tumor site: A comparison of 1362 cases across three continents.

Authors: D'Souza, Gypsyamber; Anantharaman, Devasena; Gheit, Tarik; Abedi-Ardekani, Behnoush; Beachler, Daniel C; Conway, David I; Olshan, Andrew F; Wunsch-Filho, Victor; Toporcov, Tatiana N; Ahrens, Wolfgang; Wisniewski, Kathy; Merletti, Franco; Boccia, Stefania; Tajara, Eloiza H; Zevallos, Jose P; Levi, José Eduardo; Weissler, Mark C; Wright, Sylvia; Scelo, Ghislaine; Mazul, Angela L; Tommasino, Massimo; Cadoni, Gabriella; Brennan, Paul

Published In Oral Oncol, (2016 Nov)

Abstract: To explore whether HPV-related biomarkers predict oropharyngeal squamous cell cancer (OPSCC) survival similarly across different global regions, and to explore their prognostic utility among non-oropharyngeal (non-OP) head and neck cancers.Data from 1362 head and neck SCC (HNSCC) diagnosed 2002-2011 was used from epidemiologic studies in: Brazil (GENCAPO study, n=388), U.S. (CHANCE study, n=472), and Europe (ARCAGE study, n=502). Tumors were centrally tested for p16INK4a and HPV16 DNA (by PCR). Risk of mortality was examined using Cox proportional hazard models.There were 517 OPSCC and 845 non-OP HNSCC. Cases were primarily male (81%), ever smokers (91%), with median age of 58yearsandmedian follow-up of 3.1years (IQR=1.4-5.9). Among OPSCC, the risk of mortality was significantly lower among 184 HPV-related (i.e., p16+/HPV16+) compared to 333 HPV-unrelated (p16- and/or HPV16-) cases (HR=0.25, 95%CI=0.18-0.34). Mortality was reduced among HPV-related OPSCC cases from the U.S., Europe, and Brazil (each p⩽0.01) and after adjustment, remained significantly reduced (aHR=0.34, 95%CI=0.24-0.49). Among non-OP HNSCC, neither p16 (aHR=0.83, 95%CI=0.60-1.14), HPV16 DNA (aHR=1.20, 95%CI=0.89-1.63), or p16+/HPV16+ (aHR=0.59, 95%CI=0.32-1.08) was a significantly predictor of mortality. When interaction was tested, the effect of HPV16/p16 was significantly different in OPSCC than non-OP HNSCC (p-interaction=0.02).HPV-related OPSCCs had similar survival benefits across these three regions. Prognostic utility of HPV among non-OP HNSCC is limited so tumor HPV/p16 testing should not be routinely done among non-OP HNSCC.

PubMed ID: 27865368

MeSH Terms: Aged; Alphapapillomavirus/isolation & purification*; Carcinoma, Squamous Cell/pathology*; Carcinoma, Squamous Cell/virology*; Female; Head and Neck Neoplasms/pathology*; Head and Neck Neoplasms/virology*; Humans; Male; Middle Aged; Squamous Cell Carcinoma of Head and Neck; Survival Analysis