title: High-grade acute organ toxicity and p16(INK4A) expression as positive prognostic factors in primary radio(chemo)therapy for patients with head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Superior treatment response and survival for patients with human papilloma virus (HPV)-positive head and neck cancer (HNSCC) are documented in clinical studies. However, the relevance of high-grade acute organ toxicity (HGAOT), which has also been correlated with improved prognosis, has attracted scant attention in HPV-positive HNSCC patients. Hence we tested the hypothesis that both parameters, HPV and HGAOT, are positive prognostic factors in patients with HNSCC treated with definite radiotherapy (RT) or radiochemotherapy (RCT).
  
  
  METHODS
  Pretreatment tumor tissue and clinical records were available from 233 patients receiving definite RT (62 patients) or RCT (171 patients). HPV infection was analysed by means of HPV DNA detection or p16(INK4A) expression; HGAOT was defined as the occurrence of acute organ toxicity >grade 2 according to the Common Toxicity Criteria. Both variables were correlated with overall survival (OS) using Cox proportional hazards regression.
  
  
  RESULTS
  Positivity for HPV DNA (44 samples, 18.9 %) and p16(INK4A) expression (102 samples, 43.8 %) were significantly correlated (p < 0.01), and HGAOT occurred in 77 (33 %) patients. Overall, the 5-year OS was 23 %; stratified for p16(INK4A) expression and HGAOT, OS rates were 47 %, 42 %, 20 % and 10 % for patients with p16(INK4A) expression and HGAOT, patients with HGAOT only, patients with p16(INK4A) expression only, and patients without p16(INK4A) expression or HGAOT, respectively. After multivariate testing p16(INK4A) expression (p = 0.003) and HGAOT (p < 0.001) were significantly associated with OS.
  
  
  CONCLUSIONS
  P16(INK4A) expression and HGAOT are independent prognostic factors for OS of patients with HNSCC, whereas p16(INK4A) expression is particularly important for patients without HGAOT.
authors.affiliation: Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
authors.forename: Narges
authors.initials: N
authors.lastname: Tehrany
authors.forename: Julia
authors.initials: J
authors.lastname: Kitz
authors.forename: Margret
authors.initials: M
authors.lastname: Rave-Fränk
authors.forename: Stephan
authors.initials: S
authors.lastname: Lorenzen
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Stefan
authors.initials: S
authors.lastname: Küffer
authors.forename: Clemens F
authors.initials: CF
authors.lastname: Hess
authors.forename: Peter
authors.initials: P
authors.lastname: Burfeind
authors.forename: Holger M
authors.initials: HM
authors.lastname: Reichardt
authors.forename: Martin
authors.initials: M
authors.lastname: Canis
authors.forename: Tim
authors.initials: T
authors.lastname: Beissbarth
authors.forename: Hendrik A
authors.initials: HA
authors.lastname: Wolff
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy*; D059248:Chemoradiotherapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010039:Otorhinolaryngologic Neoplasms / Q000235:genetics* / Q000628:therapy*; D011379:Prognosis; D011832:Radiation Injuries / Q000209:etiology*; D011879:Radiotherapy Dosage
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16