title: Geographic heterogeneity in the prevalence of human papillomavirus in head and neck cancer.
abstract: Human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC), although strongly divergent results have been reported regarding the prevalence of HPV16 in different countries, whether this represents important differences in etiology remains unclear. Applying rigorous protocols for sample processing, we centrally evaluated 1,420 head and neck tumors (533 oropharynx, 395 oral cavity and 482 larynx) from studies conducted in the US, Europe and Brazil for mucosal HPV DNA and p16INK4aexpression to evaluate regional heterogeneity in the proportion of HPV16-associated OPSCC and other head and neck cancer, and to assess covariates associated with the risk of HPV16-positive OPSCC. While majority of OPSCC in the US (60%) were HPV16-positive, this proportion was 31% in Europe and only 4% in Brazil (p < 0.01). Similar differences were observed for other head and neck tumors, ranging from 7% in the US and 5% in Europe, to 0% in South America. The odds of HPV16-positive OPSCC declined with increasing pack years of smoking (OR: 0.75; 95% CI: 0.64-0.87) and drink years of alcohol use (OR: 0.64; 95% CI: 0.54-0.76). These results suggest that while the contribution of HPV16 is substantial for the oropharynx, it remains limited for oral cavity and laryngeal cancers.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Devasena
authors.initials: D
authors.lastname: Anantharaman
authors.affiliation: 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.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Beachler
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Gheit
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Olshan
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.
authors.forename: Kathy
authors.initials: K
authors.lastname: Wisniewski
authors.affiliation: Department of Epidemiology, School of Public Health, University of São Paulo, São Paulo, Brazil.
authors.forename: Victor
authors.initials: V
authors.lastname: Wunsch-Filho
authors.affiliation: Department of Epidemiology, School of Public Health, University of São Paulo, São Paulo, Brazil.
authors.forename: Tatiana N
authors.initials: TN
authors.lastname: Toporcov
authors.affiliation: Department of Genetics and Evolutionary Biology, Institute of Bioscience, University of São Paulo, São Paulo, Brazil.|Department of Molecular Biology, School of Medicine of São José do Rio Preto, São José do Rio Preto, Brasil.
authors.forename: Eloiza H
authors.initials: EH
authors.lastname: Tajara
authors.affiliation: Virology Laboratory, Tropical Medicine Institute, University of São Paulo, São Paulo, Brazil.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Levi
authors.affiliation: Division of Head and Neck, Department of Surgery, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Raquel A
authors.initials: RA
authors.lastname: Moyses
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: Institute of Otorhinolaryngology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cadoni
authors.affiliation: Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Rindi
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 Medical Sciences, CeRMS and University of Turin, Turin, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Merletti
authors.affiliation: Dental School, University of Glasgow, Glasgow, United Kingdom.
authors.forename: David I
authors.initials: DI
authors.lastname: Conway
authors.affiliation: Department of Pathology, Queen Elizabeth University Hospital, Glasgow, United Kingdom.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wright
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Carreira
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Renard
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Priscilia
authors.initials: P
authors.lastname: Chopard
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: McKay-Chopin
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Scelo
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001938:Brazil; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics; D005060:Europe; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology / Q000821:virology; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D014481:United States
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: HPV16; alcohol; head and neck cancer; oropharynx; prevalence; smoking