title: Human Papillomavirus-associated oropharyngeal cancer: an observational study of diagnosis, prevalence and prognosis in a UK population.
abstract: BACKGROUND
  The incidence of Human Papillomavirus (HPV) associated oropharyngeal cancer (OPC) is increasing. HPV-associated OPC appear to have better prognosis than HPV-negative OPC. The aim of this study was to robustly determine the prevalence of HPV-positive OPC in an unselected UK population and correlate HPV positivity with clinical outcome.
  
  
  METHODS
  HPV testing by GP5+/6+ PCR, In Situ Hybridisation (ISH) and p16 immunohistochemistry (IHC) was performed on 138 OPCs diagnosed in South Wales (UK) between 2001-06. Kaplan-Meier analysis was used to correlate HPV status with clinical outcome.
  
  
  RESULTS
  Using a composite definition of HPV positivity (HPV DNA and p16 overexpression), HPV was detected in 46/83 (55%) samples where DNA quality was assured. Five year overall survival was 75.4% (95% CI: 65.2 to 85.5) in HPV-positives vs 25.3% (95% CI: 14.2 to 36.4) in HPV negatives, corresponding to a 78% reduction in death rate (HR 0.22, p < 0.001). HPV-positives had less locoregional recurrence but second HPV-positive Head and Neck primaries occurred. Poor quality DNA in fixed pathological specimens reduced both HPV prevalence estimates and the prognostic utility of DNA-based HPV testing methods. As a single marker, p16 was least affected by sample quality and correlated well with prognosis, although was not sufficient on its own for accurate HPV prevalence reporting.
  
  
  CONCLUSIONS
  This study highlights the significant burden of OPC associated with HPV infection. HPV positive cases are clinically distinct from other OPC, and are associated with significantly better clinical outcomes. A composite definition of HPV positivity should be used for accurate prevalence reporting and up-front DNA quality assessment is recommended for any DNA-based HPV detection strategy.
authors: Velindre Cancer Centre, Whitchurch, Cardiff, CF14 2TL, UK.
authors: Mererid
authors: M
authors: Evans
authors: Robert
authors: R
authors: Newcombe
authors: Alison
authors: A
authors: Fiander
authors: James
authors: J
authors: Powell
authors: Martin
authors: M
authors: Rolles
authors: Selvam
authors: S
authors: Thavaraj
authors: Max
authors: M
authors: Robinson
authors: Ned
authors: N
authors: Powell
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004279:DNA, Viral / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000821:virology*; D016609:Neoplasms, Second Primary / Q000821:virology*; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology*; D030361:Papillomavirus Infections / Q000821:virology*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D016016:Proportional Hazards Models; D016036:Seroepidemiologic Studies; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral
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