title: Impact of p16, p53, smoking, and alcohol on survival in patients with oropharyngeal squamous cell carcinoma treated with primary intensity-modulated chemoradiation.
abstract: BACKGROUND
  Analysis of the impact of risk factors on survival in patients with oropharyngeal squamous cell carcinoma (OPSCC) treated by primary intensity-modulated radiotherapy (IMRT).
  
  
  METHODS
  One hundred forty patients were included with tissue microarray (TMA) construction and immunohistochemical analysis in 124 patients (87%).
  
  
  RESULTS
  Survival analysis of patients classified into 3 risk categories according to an algorithm based on p16, smoking, T classification, and N classification revealed significant differences with a low, intermediate, and high-risk group. There was a significant impact of p53 expression as surrogate marker for smoking on outcome. In multivariate analysis, p16-positivity was a positive predictor and alcohol as well as N classification was a negative predictor for survival. The algorithm was modified based on alcohol instead of smoking with even more significant differences between the groups.
  
  
  CONCLUSIONS
  A risk model based on multiple factors instead of p16 as single marker can define different risk groups to select patients for treatment deintensification in future prospective clinical trials.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Kantonsspital St.Gallen, Switzerland.
authors.forename: Martina A
authors.initials: MA
authors.lastname: Broglie
authors.forename: Alex
authors.initials: A
authors.lastname: Soltermann
authors.forename: David
authors.initials: D
authors.lastname: Rohrbach
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Haile
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.forename: Gabriela
authors.initials: G
authors.lastname: Studer
authors.forename: Gerard F
authors.initials: GF
authors.lastname: Huber
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Sandro J
authors.initials: SJ
authors.lastname: Stoeckli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects*; D000465:Algorithms; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D000068818:Cetuximab; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000627:therapeutic use; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D016016:Proportional Hazards Models; D050397:Radiotherapy, Intensity-Modulated; D018570:Risk Assessment; D012907:Smoking / Q000009:adverse effects*; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; D000068818:Cetuximab; D002945:Cisplatin
keywords: HPV; alcohol; intensity modulated radiotherapy; oropharyngeal squamous cell carcinoma; outcome; p16; p53; risk stratification; smoking; survival