title: Impact of HPV-associated p16-expression on radiotherapy outcome in advanced oropharynx and non-oropharynx cancer.
abstract: OBJECTIVE
  HPV is found in head and neck cancer from all sites with a higher prevalence in oropharynx cancer (OPC) compared to non-OPC. HPV/p16-status has a significant impact on radiotherapy (RT) outcome in advanced OPC, but less is known about the influence in non-OPC. We analyzed HPV-associated p16-expression in a cohort of patients with stage III-IV pharynx and larynx cancer treated with primary, curatively intended (chemo-)RT, aiming to test the hypothesis that the impact of HPV/p16 also extends to tumors of non-oropharyngeal origin.
  
  
  METHODS
  1294 patients enrolled in previously conducted DAHANCA-trials between 1992 and 2012 were identified. Tumors were evaluated by p16-immunohistochemistry and classified as positive in case of staining in >70% of tumors cells.
  
  
  RESULTS
  Thirty-eight percent (490/1294) of the tumors were p16-positive with a significantly higher frequency in OPC (425/815) than in non-OPC (65/479), p<.0001. In OPC p16-positivity significantly improved loco-regional control (LRC) (adjusted HR [95% CI]: 0.43 [0.32-0.57]), event-free survival (EFS) (HR 0.44 [0.35-0.56]), and overall survival (OS) (HR: 0.38 [0.29-0.49]), respectively, compared with p16-negativity. In non-OPC no prognostic impact of p16-status was found for either endpoint: LRC (HR: 1.13 [0.75-1.70]), EFS (HR: 1.06 [0.76-1.47]), and OS (HR: 0.82 [0.59-1.16]).
  
  
  CONCLUSIONS
  The independent influence of HPV-associated p16-expression in advanced OPC treated with primary RT was confirmed. However, RT-outcome in the group of non-OPC did not differ by tumor p16-status, indicating that the prognostic impact may be restricted to OPC only.
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark. Electronic address: pernille@oncology.dk.
authors.forename: Pernille
authors.initials: P
authors.lastname: Lassen
authors.affiliation: Department of Oncology, Aarhus University Hospital, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Primdahl
authors.affiliation: Department of Oncology, Odense University Hospital, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Johansen
authors.affiliation: Department of Oncology, Rigshospitalet, Denmark.
authors.forename: Claus A
authors.initials: CA
authors.lastname: Kristensen
authors.affiliation: Department of Oncology, Herlev Hospital, Copenhagen, Denmark.
authors.forename: Elo
authors.initials: E
authors.lastname: Andersen
authors.affiliation: Department of Oncology, Aalborg Hospital, Denmark.
authors.forename: Lisbeth J
authors.initials: LJ
authors.lastname: Andersen
authors.affiliation: Department of Oncology, Oslo University Hospital, Norway.
authors.forename: Jan F
authors.initials: JF
authors.lastname: Evensen
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
authors.forename: Jesper G
authors.initials: JG
authors.lastname: Eriksen
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy*; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000532:radiotherapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000532:radiotherapy* / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins
keywords: HNSCC; HPV; Prognosis; Radiotherapy; p16