p16 cutoff in head and neck squamous cell carcinoma: correlation between tumor and patient characteristics and outcome

Int J Biol Markers. 2016 Feb 28;31(1):e44-52. doi: 10.5301/jbm.5000175.


Background: p16 has been indicated as a suitable surrogate biomarker of HPV infection. The prognosis of p16-positive oropharynx tumors (OTs) of squamous cell carcinoma (SCC) histology is better than that of p16-negative tumors.

Methods: We analyzed 209 samples of head and neck SCC to establish a predictive cutoff for p16 and determine the role of p16 positivity in OTs versus non-OTs. We compared the outcomes of tumors harboring any percentage of p16-positive cells (≥1%) with those of p16-negative OTs. We then considered 3 cutoffs (10%, 50% and 70% positive cells) to evaluate the outcome of OTs/non-OTs with similar p16 expression and p16-positive versus p16-negative tumors stratified by patient age.

Results: p16-negative tumors among OTs and non-OTs were 29% and 49%, respectively (p = 0.0054). The cumulative distribution showed that the positive values were located around 2 focus points: 2% and 96%. Subgroup analysis showed that only OTs occurred in young patients (aged <65 years) and that there was a ≥70% gain in survival in cases with p16-positive cells.

Conclusions: p16 positivity influences outcome only in young patients and OTs (p = 0.048).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cyclin-Dependent Kinase Inhibitor p16
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Papillomaviridae / genetics
  • Papillomaviridae / pathogenicity
  • Prognosis
  • Treatment Outcome


  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins
  • EGFR protein, human
  • ErbB Receptors