title: Relationship between epidermal growth factor receptor status, p16(INK4A), and outcome in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Human papilloma virus (HPV) infection is a powerful prognostic biomarker in head and neck squamous cell carcinoma (HNSCC). Increased epidermal growth factor receptor (EGFR) gene copy number and protein expression have been reported to be negative predictors of outcome. This study examined the relationship between HPV status, EGFR gene copy number, EGFR protein expression, and clinical outcome in HNSCC patients treated with chemoradiation.
  
  
  METHODS
  HPV status was determined using p16(INK4A) immunohistochemistry (IHC), EGFR gene copy number was evaluated with FISH, and EGFR protein expression by IHC in 212 subjects.
  
  
  RESULTS
  EGFR FISH was positive in 41 of 204 (20%) patients and was negatively correlated with failure-free survival (FFS; HR = 1.84, P = 0.027) and overall survival (OS; HR = 1.78, P = 0.082). For p16(INK4A), 85 of 200 (42.5%) patients were found to be p16 positive, including 75 of 131 (57%) with oropharyngeal cancer. Patients with p16-positive oropharyngeal cancer had significantly improved FFS (HR = 0.28, P < 0.001) and OS (HR = 0.31, P = 0.002). Only 2 of 126 (1.6%) oropharyngeal cancer patients were found to be p16+/EGFR FISH+. EGFR IHC was positive in 81 of 93 (87%) of patients and was associated with poorer FFS (HR = 1.98, P = 0.35) and OS (HR = 2.52, P = 0.22).
  
  
  CONCLUSIONS
  Increased EGFR gene copy number is largely restricted to p16(INK4A)-negative oropharyngeal cancer. Although p16(INK4A) and EGFR FISH are both predictive of outcome in univariate analyses, only p16(INK4A) remains independently predictive.
  
  
  CONCLUSIONS
  Knowledge of HPV and EGFR status can have implications for treatment options and prognosis in HNSCC.
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Young
authors.forename: Danny
authors.initials: D
authors.lastname: Rischin
authors.forename: Richard
authors.initials: R
authors.lastname: Fisher
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Fox
authors.forename: Lester J
authors.initials: LJ
authors.lastname: Peters
authors.forename: June
authors.initials: J
authors.lastname: Corry
authors.forename: Annette
authors.initials: A
authors.lastname: Lim
authors.forename: Kelly
authors.initials: K
authors.lastname: Waldeck
authors.forename: Benjamin
authors.initials: B
authors.lastname: Solomon
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C512478:EGFR protein, human; D066246:ErbB Receptors