title: Detection of HPV-associated oropharyngeal tumours in a 16-year cohort: more than meets the eye.
abstract: BACKGROUND
  Accurate assessment of the prevalence of the human papilloma virus (HPV) in oropharyngeal tumours (OpSCC) is important because HPV-positive OpSCC are consistently associated with an improved overall survival. Recently, an algorithm has become available that reliably detects clinically relevant HPV in tumour tissue, however, no complete cohorts have been tested. The aim was to determine the prevalence of active high-risk HPV infection in a complete cohort of OpSCC collected over a 16-year period.
  
  
  METHODS
  Using a triple algorithm of p16 immunohistochemistry, HPV-BRISH and HPV-PCR, we assessed the prevalence of active HPV infection in all OpSCC diagnosed in our hospital from 1997 to 2012 (n=193) and a random selection of 200 oral tumours (OSCC).
  
  
  RESULTS
  Forty-seven OpSCC (24%) were HPVGP PCR-positive; 42 cases were HPV16+, 1 HPV18+, 3 HPV33+ and 1 HPV35+. Brightfield in situ hybridisation did not identify additional HPV-positive cases. Human papilloma virus-associated tumour proportion increased from 13% (1997-2004) to 30% (2005-2012). Human papilloma virus-positivity was an independent predictor for longer disease-specific survival (HR=0.22; 95%CI:0.10-0.47). Only one OSCC was HPV+.
  
  
  CONCLUSIONS
  In our cohort, the incidence of HPV-associated OpSCC is low but increasing rapidly. The strict detection algorithm, analysis of disease-specific survival and the complete cohort, including palliatively treated patients, may influence the reported prevalence and prognostic value of HPV in OpSCC.
authors: 1] Department of Oral & Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700RB Groningen, The Netherlands [2] Department of Pathology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700RB Groningen, The Netherlands.
authors: L J
authors: LJ
authors: Melchers
authors: Department of Pathology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700RB Groningen, The Netherlands.
authors: M F
authors: MF
authors: Mastik
authors: Department of Pathology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700RB Groningen, The Netherlands.
authors: B
authors: B
authors: Samaniego Cameron
authors: 1] Department of Research, Comprehensive Cancer Center The Netherlands, P.O. Box 19079, 3501 DB Utrecht, The Netherlands [2] Department of Epidemiology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700RB Groningen, The Netherlands.
authors: B A C
authors: BA
authors: van Dijk
authors: Department of Epidemiology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700RB Groningen, The Netherlands.
authors: G H
authors: GH
authors: de Bock
authors: Department of Otorhinolaryngology/Head & Neck surgery, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700RB Groningen, The Netherlands.
authors: B F A M
authors: BF
authors: van der Laan
authors: Department of Pathology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700RB Groningen, The Netherlands.
authors: B
authors: B
authors: van der Vegt
authors: Department of Pathology, Maastricht University Medical Center, P.O. Box 5800, 6202AZ Maastricht, The Netherlands.
authors: E J M
authors: EJ
authors: Speel
authors: Department of Oral & Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700RB Groningen, The Netherlands.
authors: J L N
authors: JL
authors: Roodenburg
authors: Department of Oral & Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700RB Groningen, The Netherlands.
authors: M J H
authors: MJ
authors: Witjes
authors: Department of Pathology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700RB Groningen, The Netherlands.
authors: E
authors: E
authors: Schuuring
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D052685:Alphapapillomavirus / Q000145:classification / Q000302:isolation & purification*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000821:virology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000453:epidemiology / Q000821:virology*; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000821:virology; D011379:Prognosis; D011446:Prospective Studies