title: HPV-associated head and neck cancers in the Asia Pacific: A critical literature review & meta-analysis.
abstract: BACKGROUND
  Malignancies of the upper aero-digestive tract are a major public health problem, especially in the Asia Pacific. Certain Human papillomaviruses (HPVs) are well-established risk factors for carcinoma of the uterine cervix and for a subset of head and neck carcinomata: however their true importance in different populations and anatomical subsites remains unclear. The major risk factors in Asia Pacific remain smoked/smokeless tobacco, areca nut, alcohol abuse and poor diet, with limited evidence for HPVs. We review published studies of association of HPV with anatomical site-specific Head & Neck Squamous Cell Carcinoma (HNSCC) in these populations and attempt a meta-analysis.
  
  
  METHODS
  From MEDLINE/PubMed/WEB-of SCIENCE/EMBASE/Scopus databases we found 67 relevant studies with a total of 7280 cases: 15 case-control studies met our inclusion criteria for meta-analysis, totaling 1106 cases & 638 controls. HPV detection rates, sample site and size, and methods of tissue preservation and HPV detection were tabulated for each study.
  
  
  RESULTS
  Studies were heterogeneous in terms of sample selection and method of detection of HPVs. Most were of limited quality. Averaging data from 67 studies of HNSCC, the prevalence of HPV of any subtype is approximately 36%. PCR (polymerase chain reaction) was the most used detection method and HPV16 the most common genotype reported. Meta-analyses of case-control studies from this region reveal significant heterogeneity but suggest higher HPV prevalence in oropharyngeal cancer (OR: 14.66; 95%CI: 6.09-35.26) compared to oral cavity cancer and laryngeal cancer; (OR: 4.06; 95%CI: 3.05-5.39 & OR: 3.23; 95%CI: 1.37-7.61) respectively.
  
  
  CONCLUSIONS
  In view of the significant association of HPV with HNSCC, studies with accurate subsite classification and more sensitive detection methods are necessary. Accurate data from this geographical region are essential to inform public health policies and treatment decisions, especially as studies from Europe and North America reveal HPV-driven cancers to be less aggressive, permitting treatment de-intensification.
authors.affiliation: School of Dentistry & Oral Health, Griffith University, Gold Coast Campus, Queensland, Australia; School of Medical Science, Griffith University, Gold Coast Campus, Queensland, Australia; Cancer Research Centre, Molecular Basis of Disease program, Menzies Health Institute Queensland, Griffith University, Queensland, Australia. Electronic address: m.shaikh@griffith.edu.au.
authors.forename: Mushfiq Hassan
authors.initials: MH
authors.lastname: Shaikh
authors.affiliation: School of Medical Science, Griffith University, Gold Coast Campus, Queensland, Australia; Cancer Research Centre, Molecular Basis of Disease program, Menzies Health Institute Queensland, Griffith University, Queensland, Australia. Electronic address: n.mcmillan@griffith.edu.au.
authors.forename: Nigel A J
authors.initials: NA
authors.lastname: McMillan
authors.affiliation: Cancer Research Centre, Molecular Basis of Disease program, Menzies Health Institute Queensland, Griffith University, Queensland, Australia; Population & Social Health Research program, Menzies Health Institute Queensland, Griffith University, Queensland, Australia. Electronic address: n.johnson@griffith.edu.au.
authors.forename: Newell W
authors.initials: NW
authors.lastname: Johnson
mesh_terms: D001208:Asia / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000821:virology*; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology* / Q000821:virology; D016133:Polymerase Chain Reaction; D015995:Prevalence; D000077195:Squamous Cell Carcinoma of Head and Neck
keywords: Asia pacific populations; Head and neck squamous cell carcinoma; Human papillomavirus; Meta-analysis; Polymerase chain reaction (PCR)