title: Improved survival in HPV/p16-positive oropharyngeal cancer patients treated with postoperative radiotherapy.
abstract: BACKGROUND
  In the literature, HPV infection and/or p16 positivity have been consistently demonstrated to correlate with improved response rates in oropharyngeal squamous cell carcinoma (OPSCC) patients treated with primary radiotherapy (RT) alone and in combination with chemotherapy. However, the exact role of HPV/p16 positivity in patients treated with postoperative RT is still unclear.
  
  
  METHODS
  We analyzed tumor samples for HPV-DNA and p16 expression and correlated these variables with treatment outcome in a series of 63 consecutively treated oropharyngeal cancer patients (95% stage III/IV). HPV and p16 analysis were performed using validated test systems. Survival was estimated by the Kaplan-Meier method. Cox proportional hazard regression models were applied to compare the risk of death among patients stratified according to risk factors.
  
  
  RESULTS
  Expression of p16 or high-risk HPV-DNA was detected in 60.3% and 39.6% of the tumors, respectively. p16 expression [overall survival (OS) at 2 years: 91%] as well as HPV infection (OS at 2 years: 95%) was associated with improved OS. Mean survival in p16-positive patients was 112 months compared to 64.6 months in case of p16 negativity. All HPV-positive tumors stained positive for p16. In a multivariable analysis, p16 positivity was associated with improved OS and with disease-free survival.
  
  
  CONCLUSIONS
  p16 expression and HPV infection are strongly associated with the outcome of postoperatively irradiated OPSCC patients. HPV and p16 double-negative OPSCC patients should be regarded as a distinct "very high-risk patient group" that may benefit from intensified or novel treatment combinations.
authors.affiliation: Departments of Otorhinolaryngology: Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Heiduschka
authors.forename: Anja
authors.initials: A
authors.lastname: Grah
authors.forename: Felicitas
authors.initials: F
authors.lastname: Oberndorfer
authors.forename: Lorenz
authors.initials: L
authors.lastname: Kadletz
authors.forename: Gabriela
authors.initials: G
authors.lastname: Altorjai
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kornek
authors.forename: Fritz
authors.initials: F
authors.lastname: Wrba
authors.forename: Dietmar
authors.initials: D
authors.lastname: Thurnher
authors.forename: Edgar
authors.initials: E
authors.lastname: Selzer
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D003131:Combined Modality Therapy; D005260:Female; D052162:Human papillomavirus 16; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery* / Q000821:virology; D030361:Papillomavirus Infections / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery* / Q000821:virology; D018714:Radiotherapy, Adjuvant; D015996:Survival Rate