p16 expression in cutaneous squamous carcinomas with neck metastases: a potential pitfall in identifying unknown primaries of the head and neck

Head Neck. 2013 Nov;35(11):1527-33. doi: 10.1002/hed.23188. Epub 2012 Oct 29.

Abstract

Background: Human papillomavirus (HPV) positivity (+) has been used to identify oropharyngeal squamous carcinomas (SCCs) presenting as unknown primaries in the neck. p16 overexpression correlates with HPV+ in the oropharynx; however, the use of p16 alone as a surrogate marker of oropharyngeal HPV+ tumors has not been validated.

Methods: We immunohistochemically analyzed p16 expression in surgically resected aggressive cutaneous head and neck SCC primaries and their nodal metastases from 24 patients to determine the potential overlap of p16 expression outside of the oropharynx.

Results: Five of 24 primary tumors (20.8%) and 3 lymph node metastases (12.5%) in levels II, III, and V, and the periparotid region diffusely expressed p16. HPV (high-risk types by in situ hybridization) was negative.

Conclusions: p16 expression is relatively common in lymph node-positive cutaneous head and neck SCCs; thus, p16 expression as an independent biomarker and mechanism to determine the oropharyngeal source of an unknown primary is not advised.

Keywords: cutaneous squamous carcinoma; neck metastases; p16; unknown primary.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biopsy, Needle
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Databases, Factual
  • Disease-Free Survival
  • Female
  • Head and Neck Neoplasms / chemistry
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / secondary
  • Head and Neck Neoplasms / virology
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / isolation & purification
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Neoplasms, Unknown Primary / chemistry*
  • Neoplasms, Unknown Primary / mortality
  • Neoplasms, Unknown Primary / pathology
  • Neoplasms, Unknown Primary / virology
  • Oropharyngeal Neoplasms / chemistry
  • Oropharyngeal Neoplasms / mortality
  • Oropharyngeal Neoplasms / secondary*
  • Oropharyngeal Neoplasms / virology
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / pathology
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Skin Neoplasms / chemistry*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Survival Analysis

Substances

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