title: Human papillomavirus status and p16(INK4A) expression in patients with mucosal squamous cell carcinoma of the head and neck in Queensland, Australia.
abstract: BACKGROUND
  The last decade has seen changes in the epidemiology of mucosal squamous cell carcinomas of the head and neck (HNSCCs), with increasing numbers of cases attributable to human papillomavirus (HPV) infection. We sought to determine the prevalence of HPV and p16(INK4a) expression in Australian HNSCC patients and to identify predictors of HPV-positivity.
  
  
  METHODS
  We recruited 248 HNSCC patients with histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx or larynx diagnosed between 2004 and 2010. All patients completed a questionnaire. Clinical data were abstracted from medical records. HPV presence in paraffin-embedded tumours was determined by PCR, and expression of p16(INK4a), p21(WAF1), p53, pRB, cyclin D1, and Ki67 by immunohistochemistry.
  
  
  RESULTS
  Fifty (20%) patients were HPV-positive, 63 (28%) overexpressed p16(INK4a), and 44 (19%) were positive for HPV and p16(INK4a) (high concordance between HPV-positivity and p16(INK4a) status, κ=0.72). HPV-16 was most common (84%), followed by HPV-18 (10%), HPV-33 (4%) and HPV-69 (2%). HPV and p16(INK4a) prevalence was highest for SCCs of the oropharynx, followed by hypopharynx, larynx and oral cavity (HPV and p16(INK4a)p<0.0001). HPV prevalence and p16(INK4a)-overexpression were significantly higher in younger than older patients (HPV p=0.001; p16 (INK4a)p=0.003). Heavy smokers had lower HPV prevalence than non- or moderate smokers (p=0.017). Gender and alcohol consumption were not associated with HPV or p16(INK4a) status. HPV-positive tumours had significantly lower cyclin D1 and higher p21(WAF1) expression than HPV-negative tumours.
  
  
  CONCLUSIONS
  HPV prevalence and p16(INK4a)-overexpression were highest in oropharyngeal tumours, younger patients, and non-smokers.
authors: Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia. Electronic address: Annika.Antonsson@qimrberghofer.edu.au.
authors: Annika
authors: A
authors: Antonsson
authors: Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Rachel E
authors: RE
authors: Neale
authors: Princess Alexandra Hospital, Brisbane, Australia.
authors: Samuel
authors: S
authors: Boros
authors: Princess Alexandra Hospital, Brisbane, Australia.
authors: Guy
authors: G
authors: Lampe
authors: Princess Alexandra Hospital, Brisbane, Australia.
authors: William B
authors: WB
authors: Coman
authors: Princess Alexandra Hospital, Brisbane, Australia.
authors: David I
authors: DI
authors: Pryor
authors: Princess Alexandra Hospital, Brisbane, Australia.
authors: Sandro V
authors: SV
authors: Porceddu
authors: Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: David C
authors: DC
authors: Whiteman
mesh_terms: D001315:Australia; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D008297:Male; D011793:Queensland; D012307:Risk Factors; D012907:Smoking; D000077195:Squamous Cell Carcinoma of Head and Neck
keywords: Cyclin D1; Human papillomavirus DNA tests; Immunohistochemistry; Papillomavirus infections; Risk factors; Smoking; Squamous cell carcinoma of the head and neck; p16(INK4A)