Expression of EGFR and HPV-associated p16 in oropharyngeal carcinoma: correlation and influence on prognosis after radiotherapy in the randomized DAHANCA 5 and 7 trials

Radiother Oncol. 2013 Sep;108(3):489-94. doi: 10.1016/j.radonc.2013.08.036. Epub 2013 Sep 20.


Aim: EGFR and HPV-associated p16 are among the most investigated biomarkers in head and neck cancer. The aim was to investigate the correlation and interaction between these two markers and to evaluate their potential prognostic significance when combined.

Materials and methods: 336 Oropharyngeal carcinomas treated with primary radiotherapy (66-68 Gy, 2fx/day, 10-12 Gy/week) and with known EGFR/p16-status estimated semiquantitatively by immunohistochemistry were included in the study. Data were evaluated by EGFR-expression (high/low) and p16-status (positive/negative) consequently dividing tumours into four groups by combination of the biomarkers. Patient/tumour characteristics and complete 5-year follow-up were available.

Results: Low EGFR-expression was significantly more common in p16-positive tumours compared to p16-negative, p < 0.0001. p16 positivity showed a strong prognostic impact (p < 0.0001, HR = 0.22 [0.13-0.38]), whereas EGFR was a weak prognostic marker when local control was used as endpoint (p = 0.03, HR = 0.53 [0.29-0.94]). Combination of EGFR/p16 did not add significant information to p16 alone and by multivariable analysis only p16 showed significant prognostic information for all evaluated endpoints.

Conclusions: Both EGFR and p16 bear prognostic information in oropharyngeal cancer, although p16 is, by far, the strongest prognostic factor. The markers seem to be correlated and this might have influence when evaluating the effect of EGFR inhibition in oropharyngeal tumours.

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cyclin-Dependent Kinase Inhibitor p16
  • ErbB Receptors / analysis*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Oropharyngeal Neoplasms / chemistry
  • Oropharyngeal Neoplasms / mortality
  • Oropharyngeal Neoplasms / radiotherapy*
  • Oropharyngeal Neoplasms / virology
  • Papillomaviridae / isolation & purification*
  • Prognosis
  • Randomized Controlled Trials as Topic


  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins
  • P16 protein, human
  • ErbB Receptors