The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: evaluation of the randomised DAHANCA 6&7 trial

Radiother Oncol. 2011 Jul;100(1):49-55. doi: 10.1016/j.radonc.2011.02.010. Epub 2011 Mar 21.


Background and purpose: Tumour HPV-positivity is a favourable prognostic factor in the radiotherapy of HNSCC, but the optimal radiotherapy regimen for HPV-positive HNSCC is not yet defined. Reducing overall treatment time is known to improve outcome in the radiotherapy of HNSCC as was also demonstrated in the randomised DAHANCA 6&7 trial. We aimed to assess the influence of tumour HPV-status, expressed by p16, on the response to accelerated fractionated radiotherapy in HNSCC through evaluation of the DAHANCA 6&7 trial.

Materials and methods: Immunohistochemical detection of HPV-associated p16-expression was performed on FFPE-pre-treatment tumour-tissues from 794 patients enrolled in the DAHANCA 6&7 trial. The influence of tumour p16-status on loco-regional tumour control and survival as a function of fractionation schedule (5Fx/week vs 6Fx/week) was evaluated 5years after the completion of radiotherapy.

Results: The significant and independent prognostic value of tumour p16-positivity in HNSCC radiotherapy was confirmed, with adjusted hazard ratios (HR) of 0.58 [0.43-0.78], 0.47 [0.33-0.67] and 0.54 [0.42-0.68] for loco-regional control, disease-specific and overall survival, respectively. Accelerated radiotherapy significantly improved loco-regional tumour control compared to conventional radiotherapy, adjusted HR: 0.73 [0.59-0.92] and the benefit of the 6Fx/week regimen was observed both in p16-positive (HR: 0.56 [0.33-0.96]) as well as in p16-negative tumours (HR: 0.77 [0.60-0.99]). Disease-specific survival was also significantly improved with accelerated radiotherapy in the group of p16-positive tumours (adjusted HR: 0.43 [0.22-0.82]).

Conclusion: Accelerated radiotherapy significantly improves outcome in HNSCC compared to conventional fractionation. The observed benefit is independent of tumour p16-status and the use of a moderately accelerated radiotherapy regimen seems advantageous also for HPV/p16-positive HNSCC.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / radiotherapy*
  • Carcinoma, Squamous Cell / virology
  • Cyclin-Dependent Kinase Inhibitor p16
  • Dose Fractionation, Radiation*
  • Female
  • Head and Neck Neoplasms / chemistry
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / radiotherapy*
  • Head and Neck Neoplasms / virology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Papillomaviridae / isolation & purification*
  • Proportional Hazards Models
  • Squamous Cell Carcinoma of Head and Neck


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