p16 status, pathologic and clinical characteristics, biomolecular signature, and long-term outcomes in head and neck squamous cell carcinomas of unknown primary

Head Neck. 2014 Dec;36(12):1677-84. doi: 10.1002/hed.23514. Epub 2014 Jan 13.

Abstract

Background: The purpose of this study was to report associations between p16 status, clinicopathologic characteristics, and outcomes for head and neck squamous cell carcinoma of unknown primary (CUP).

Methods: Specimens of squamous cell CUP were reanalyzed. Human papillomavirus (HPV) status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in head and neck squamous cell carcinoma (HNSCC).

Results: A majority of the population (n = 26; 74%) was p16 positive (+). Prognostic factors benefiting survival were p16+ status (p < .0001), absence of macroscopic extracapsular extension (ECE; p = .004), younger age (p = .01), and higher grade (p = 0.007). The prognostic implication of worse overall survival (OS) with macroscopic ECE (p = .009) remained significant when limited to patients who were p16+ (p = .002). Exploratory TMA between unknown primary and controls suggested a biomolecular difference between squamous cell CUP and known-primary cancer.

Conclusion: The majority of patients with squamous cell CUP were p16+, indicative of HPV association. P16 staining and ECE seem to be the most prognostic features in squamous cell CUP.

Keywords: concurrent chemotherapy; extracapsular extension (ECE); human papillomavirus (HPV); tissue microarray; unknown primary.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Female
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Male
  • Neoplasm Proteins / metabolism*
  • Neoplasms, Unknown Primary / metabolism*
  • Neoplasms, Unknown Primary / mortality
  • Neoplasms, Unknown Primary / pathology*
  • Papillomavirus Infections
  • Squamous Cell Carcinoma of Head and Neck
  • Survival Analysis
  • Tissue Array Analysis

Substances

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