title: Effect of HPV on head and neck cancer patient survival, by region and tumor site: A comparison of 1362 cases across three continents.
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 p16INK4aand 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.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA.
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
authors.affiliation: Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
authors.forename: Devasena
authors.initials: D
authors.lastname: Anantharaman
authors.affiliation: Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Gheit
authors.affiliation: Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon, France.
authors.forename: Behnoush
authors.initials: B
authors.lastname: Abedi-Ardekani
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Beachler
authors.affiliation: School of Medicine, Dentistry, and Nursing, University of Glasgow, Glasgow, UK.
authors.forename: David I
authors.initials: DI
authors.lastname: Conway
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Olshan
authors.affiliation: Department of Epidemiology, School of Public Health, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Victor
authors.initials: V
authors.lastname: Wunsch-Filho
authors.affiliation: Department of Epidemiology, School of Public Health, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Tatiana N
authors.initials: TN
authors.lastname: Toporcov
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany; Institute for Statistics, University Bremen, Bremen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ahrens
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Wisniewski
authors.affiliation: CeRMS and Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Merletti
authors.affiliation: Section of Hygiene-Institute of Public Health, Faculty of Medicine, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Boccia
authors.affiliation: Department of Molecular Biology, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, São Paulo, Brazil.
authors.forename: Eloiza H
authors.initials: EH
authors.lastname: Tajara
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Jose P
authors.initials: JP
authors.lastname: Zevallos
authors.affiliation: Virology Lab, Tropical Medicine Institute, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Levi
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Weissler
authors.affiliation: Department of Pathology, Queen Elizabeth University Hospital, Glasgow, UK.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wright
authors.affiliation: Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Scelo
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Mazul
authors.affiliation: Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.affiliation: Head and Neck Surgery Department, Institute of Otorhinolaryngology, Università Cattolica del Sacro Cuore, Fondazione Policlinico “A. Gemelli”, Rome, Italy
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cadoni
authors.affiliation: Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
mesh_terms: D000368:Aged; D052685:Alphapapillomavirus / Q000302:isolation & purification*; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis
keywords: Brazil; Europe; HNSCC; HPV; Non-OP; Oral HPV; P16; Prognostic; Risk factors; Survival