Significance of p16 expression in head and neck cancer patients treated with radiotherapy and cetuximab

Strahlenther Onkol. 2014 Sep;190(9):832-8. doi: 10.1007/s00066-014-0652-y. Epub 2014 Apr 9.

Abstract

Background: HPV-infection, p16 positivity, and EGFR expression have been correlated with favorable responses of head and neck cancer patients treated with radiotherapy (RT) with or without chemotherapy. However, a possible correlation of HPV/p16 and EGFR status on the effect of RT in combination with cetuximab has not been sufficiently investigated.

Materials and methods: We analyzed tumor samples for p16 and EGFR expression and correlated these variables with treatment outcome. Cox-proportional-hazard regression models were applied to compare the risk of death among patients stratified according to risk factors. Survival was estimated by the Kaplan-Meier method. Results were compared with an institutional historical control group treated without cetuximab and with published data.

Results: Expression of p16 was predominantly found in oropharyngeal squamous cell cancer patients (OPSCC; 36.6% positivity; 92% of all cases), while EGFR was expressed at high levels in all tumor subsites (82%). p16 expression was associated with improved overall survival in irradiated OPSCC patients (2-year overall survival of 80% in p16-positive vs. 33% overall survival in p16-negative patients). In a multivariable analysis covering all tumor sites, nodal stage (> N2a vs. ≤ N2a) and tumor site (OPSSC vs. non-OPSCC) had an impact on overall survival.

Conclusion: Our results show that p16 positivity is associated with a favorable outcome in OPSCC patients treated with RT and cetuximab.

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Cetuximab
  • Chemoradiotherapy*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • ErbB Receptors
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Staging
  • Otorhinolaryngologic Neoplasms / genetics
  • Otorhinolaryngologic Neoplasms / mortality
  • Otorhinolaryngologic Neoplasms / pathology
  • Otorhinolaryngologic Neoplasms / therapy*

Substances

  • Antibodies, Monoclonal, Humanized
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins
  • EGFR protein, human
  • ErbB Receptors
  • Cetuximab