Association of p16(INK4a) overexpression with improved outcomes in young patients with squamous cell cancers of the oral tongue

Head Neck. 2011 Nov;33(11):1622-7. doi: 10.1002/hed.21650. Epub 2010 Dec 28.


Background: The aim of this study was to examine biomolecular profiles in a cohort of young adults with squamous cell cancers (SCCs) of the oral tongue.

Methods: We identified all patients aged 18 to 39 years diagnosed with SCC of the oral tongue at our institution. Immunohistochemical (IHC) staining was performed for p16(INK4a) , epidermal growth factor receptor (EGFR), phosphorylated-EGFR (pEGFR), p53, and ERCC1. Human papillomavirus (HPV) testing was performed using in situ hybridization (ISH) and polymerase chain reaction (PCR). Biomarker expression and HPV status were correlated with outcomes.

Results: We identified 25 patients with sufficient tumor samples. Median age at diagnosis was 30 years (range, 20-39 years). p16(INK4a) overexpression was observed in 11 of 25 patients, whereas HPV-16 positivity was observed in none of the tumor samples by ISH and 2 of the tumor samples by PCR. p16(INK4a) positivity was correlated with improved relapse-free survival (hazard ratio [HR] = 0.23, p = .01) and overall survival (HR = 0.28, p = .05). Neither EGFR, pEGFR, p53, nor excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) expression correlated with outcome on univariate analysis.

Conclusions: p16(INK4a) overexpression was common and was a marker of favorable prognosis. p16(INK4a) overexpression was not a reliable predictor of HPV positivity in our cohort.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Biomarkers, Tumor / analysis
  • Biopsy, Needle
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Cohort Studies
  • DNA, Viral / analysis
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, p16*
  • Humans
  • Immunohistochemistry
  • Male
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / diagnosis
  • Polymerase Chain Reaction / methods
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • Serologic Tests
  • Statistics, Nonparametric
  • Survival Analysis
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / mortality
  • Tongue Neoplasms / pathology
  • Tongue Neoplasms / therapy
  • Young Adult


  • Biomarkers, Tumor
  • DNA, Viral