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Effect of HPV on Head and Neck Cancer Patient Survival, by Region and Tumor Site: A Comparison of 1362 Cases across Three Continents


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, et al. (2016). Effect of HPV on Head and Neck Cancer Patient Survival, by Region and Tumor Site: A Comparison of 1362 Cases across Three Continents. Oral Oncology, 62, 20-27. PMCID: PMC5123752


OBJECTIVES: 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.
METHODS: 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.
RESULTS: 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 p0.01) 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).
CONCLUSION: 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.


Reference Type

Journal Article

Year Published


Journal Title

Oral Oncology


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, Jose Eduardo
Weissler, Mark Christian
Wright, Sylvia
Scelo, Ghislaine
Mazul, Angela L.
Tommasino, Massimo
Brennan, Paul
Cadoni, Gabriella