Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-1

Br J Cancer. 2015 Jul 14;113(2):321-6. doi: 10.1038/bjc.2015.207. Epub 2015 Jun 9.


Background: Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased.

Methods: Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry.

Results: No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC.

Conclusion: Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged ⩽40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / virology*
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral / analysis
  • Female
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / virology*
  • Human papillomavirus 16 / isolation & purification*
  • Humans
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / physiology*
  • Papillomavirus Infections / complications*
  • Receptors, Virus / physiology*
  • Squamous Cell Carcinoma of Head and Neck
  • Syndecan-1 / analysis
  • Syndecan-1 / physiology*
  • Tongue Neoplasms / mortality
  • Tongue Neoplasms / virology*


  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Neoplasm Proteins
  • Receptors, Virus
  • Syndecan-1