title: Geographic variation in human papillomavirus-related oropharyngeal cancer: Data from 4 multinational randomized trials.
abstract: There are variations in the proportions of head and neck cancers caused by the human papillomavirus (HPV) between countries and regions. It is unclear if these are true variations or due to different study designs and assays.
  
  
  
  We tested formalin-fixed paraffin-embedded diagnostic biopsies for p16 immunohistochemistry and HPV-DNA (by polymerase chain reaction [PCR] and in situ hybridization [ISH]) using validated protocols on samples from 801 patients with head and neck cancer recruited prospectively between 2006 and 2011 in 4 randomized controlled trials (RCTs).
  
  
  
  Twenty-one percent of patients (170 of 801) showed both HPV-DNA and p16-positivity, detected almost exclusively in oropharyngeal cancer (55%; 15 of 302); and only 1% of the patients (5 of 499) with nonoropharyngeal cancer were HPV positive. HPV-positive oropharyngeal cancer differed between Western and Eastern Europe (37%, 155 of 422 vs 6%, 8 of 144; p < .0001) and between Western Europe and Asia (37% vs 2%; 4 of 217; p < .0001). Other independent determinants of HPV positivity were tumor site and smoking.
  
  
  
  This is the first study to establish geographic variability as an independent risk factor in HPV-positive oropharyngeal cancer prevalence, with higher prevalence in Western Europe. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E1863-E1869, 2016.
authors.affiliation: Institute of Head and Neck Studies and Education (InHANSE), School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Hisham
authors.initials: H
authors.lastname: Mehanna
authors.affiliation: Roche Products Ltd, Shire Park, Welwyn Garden City, United Kingdom.
authors.forename: Natalie
authors.initials: N
authors.lastname: Franklin
authors.affiliation: PPD, Granta Park, Great Abington, Cambridge, United Kingdom.
authors.forename: Natalie
authors.initials: N
authors.lastname: Compton
authors.affiliation: Centre for Oral Health Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Max
authors.initials: M
authors.lastname: Robinson
authors.affiliation: HPV Oncology Group, Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Ned
authors.initials: N
authors.lastname: Powell
authors.affiliation: GSK, Uxbridge, Middlesex, United Kingdom.
authors.forename: Nigel
authors.initials: N
authors.lastname: Biswas-Baldwin
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Newcastle upon Tyne Hospitals, NHS Trust, and Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Vindh
authors.initials: V
authors.lastname: Paleri
authors.affiliation: Hall-Edwards Radiotherapy Research Group, Old Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hartley
authors.affiliation: Department of Oncology, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom.
authors.forename: Lydia
authors.initials: L
authors.lastname: Fresco
authors.affiliation: Bristol Haematology and Oncology Centre, Bristol, United Kingdom.
authors.forename: Hoda
authors.initials: H
authors.lastname: Al-Booz
authors.affiliation: Edinburgh Cancer Centre, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Junor
authors.affiliation: Department of Clinical Research, Synta Pharmaceuticals Corp, Lexington, Massachusetts.
authors.forename: Iman
authors.initials: I
authors.lastname: El-Hariry
authors.affiliation: School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Sally
authors.initials: S
authors.lastname: Roberts
authors.affiliation: The Institute of Cancer Research, London, United Kingdom.
authors.forename: Kevin
authors.initials: K
authors.lastname: Harrington
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: K Kian
authors.initials: KK
authors.lastname: Ang
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Gibbet Hill Campus, Coventry, United Kingdom.
authors.forename: Janet
authors.initials: J
authors.lastname: Dunn
authors.affiliation: School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Ciaran
authors.initials: C
authors.lastname: Woodman
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D005060:Europe; D005843:Geography; D006801:Humans; D007150:Immunohistochemistry; D009959:Oropharyngeal Neoplasms / Q000453:epidemiology* / Q000821:virology; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications*; D016032:Randomized Controlled Trials as Topic
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral
keywords: head and neck cancer; human papillomavirus; oropharynx; prevalence; squamous cell carcinoma