title: The prognostic significance of hypoxia inducing factor 1-α in oropharyngeal cancer in relation to human papillomavirus status.
abstract: OBJECTIVE
  This study examines the prognostic significance of hypoxia inducing factor-1α (HIF-1α) expression in relation to human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (SCC).
  
  
  METHODS
  Clinical details on 233 oropharyngeal SCCs were extracted from institutional databases. Recurrence in any form or death from any cause was recorded for a median of 51 months after diagnosis. HIF-1α expression was evaluated by semiquantitative immunohistochemistry and HPV status was determined by HPV E6-targeted multiplex real-time PCR and p16 immunohistochemistry. Determinants of recurrence and mortality hazards were modeled using Cox regression with censoring at dates of last follow-up.
  
  
  RESULTS
  The HIF-1α positivity rate was 58.8%. HIF-1α positivity was associated with higher T category (T3/T4 vs. T1/T2, 64.2% vs. 48.4%, p=0.001) and lower grade (Grade 1-2 vs. 3, 62% vs. 46.9%, p=0.001). There was no significant association between HIF-1α expression and HPV status. After adjustment for clinico-pathological variables, HPV status but not HIF-1α was a strong predictor of outcome. The combination of HPV and HIF-1α was not a prognostic variable but the worst outcomes were seen in those with HPV negative and HIF-1α positive cancers. There was no statistically significant evidence of an interaction between HPV and HIF-1α.
  
  
  CONCLUSIONS
  The degree of hypoxia as measured by HIF-1α expression does not differ between HPV positive and HPV negative cancers. The role of hypoxia in HPV negative oropharyngeal cancer warrants further investigation.
authors.affiliation: Central Clinical School, The University of Sydney, Sydney, Australia. ahon6809@mail.usyd.edu.au
authors.forename: Angela
authors.initials: A
authors.lastname: Hong
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Veillard
authors.forename: Jahanfar
authors.initials: J
authors.lastname: Jahanbani
authors.forename: C Soon
authors.initials: CS
authors.lastname: Lee
authors.forename: Deanna
authors.initials: D
authors.lastname: Jones
authors.forename: Gerald
authors.initials: G
authors.lastname: Harnett
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clark
authors.forename: Michael
authors.initials: M
authors.lastname: Elliott
authors.forename: Chris
authors.initials: C
authors.lastname: Milross
authors.forename: Barbara
authors.initials: B
authors.lastname: Rose
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000821:virology; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009959:Oropharyngeal Neoplasms / Q000378:metabolism* / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit