HPV-related Oropharyngeal Squamous Cell Carcinoma: p16INK4A Immunohistochemistry or HPV Genotyping?

Anticancer Res. 2015 Sep;35(9):4733-9.


Background: Infection with high-risk human papillomavirus (HPV) is linked to a sub-group of squamous cell oropharyngeal tumors (OPSCC). Our aim was to compare an HPV Polymerase Chain Reaction (PCR) assay and p16(INK4A) expression status by immunohistochemistry (IHC) as a surrogate marker.

Materials and methods: This was a retrospective study considering patients affected by squamous cell oropharyngeal tumors. All included samples were processed for IHC for p16(INK4A) and tested by PCR for detection of HPV DNA and HPV genotyping.

Results: A total of 84 patients affected by squamous cell oropharyngeal tumors were included and tested. A significant positive correlation was found between HPV PCR and p16(INK4A) IHC but the agreement was poor (k coefficient of 0.25). In fact, the sensitivity of p16(INK4A) IHC positivity in detecting HPV PCR positivity was low (28.21%, 95% confidence interval=16.54% - 43.78%).

Conclusion: Positivity of p16(INK4A) by IHC had a low sensitivity in detecting HPV DNA and our results suggest the need at least to test p16(INK4A) IHC- negative samples using HPV PCR to increase detection accuracy and provide valuable information for the clinical management of these patients.

Keywords: HPV PCR assay; HPV infection; diagnostic assay; p16 immunohistochemistry; squamous cell oropharyngeal tumors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / virology*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Female
  • Genotype
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / metabolism
  • Oropharyngeal Neoplasms / pathology*
  • Oropharyngeal Neoplasms / virology*
  • Papillomaviridae / genetics*


  • Cyclin-Dependent Kinase Inhibitor p16