Impact of HPV-associated p16-expression on radiotherapy outcome in advanced oropharynx and non-oropharynx cancer

Radiother Oncol. 2014 Dec;113(3):310-6. doi: 10.1016/j.radonc.2014.11.032. Epub 2014 Nov 26.


Background and purpose: 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.

Material and 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.

Keywords: HNSCC; HPV; Prognosis; Radiotherapy; p16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cohort Studies
  • Cyclin-Dependent Kinase Inhibitor p16
  • Disease-Free Survival
  • Female
  • Gene Expression / genetics
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / radiotherapy*
  • Head and Neck Neoplasms / virology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Oropharyngeal Neoplasms / genetics*
  • Oropharyngeal Neoplasms / radiotherapy*
  • Oropharyngeal Neoplasms / virology
  • Papillomaviridae / genetics
  • Survival Analysis
  • Treatment Outcome


  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins