Investigation of p16(INK4a) as a prognostic biomarker in oral epithelial dysplasia

Research output: Contribution to journalArticlepeer-review

Authors

  • Hazel Williams
  • Keith Webster
  • David Pearson
  • Alec High
  • Kenneth MacLennan
  • Burcu Senguven
  • Christopher McConkey
  • Pamela Rabbitts

Colleges, School and Institutes

External organisations

  • University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

Abstract

BACKGROUND: Human papilloma virus is a risk factor for oropharyngeal cancer. Evidence for a similar aetiological role in the development of oral dysplasia or its transformation to oral cancer is not as clear. Meta-analyses estimate the prevalence of high-risk human papilloma virus (HPV) serotypes to be three times higher in pre-malignant lesions and cancer than in normal oral mucosa. However, this does not imply a causal relationship. Conflicting results are reported from the few studies examining the prognostic significance of HPV positivity in the development of oral cancer. We aimed to examine the ability of p16(INK4a) protein expression, a surrogate marker of HPV infection, to predict malignant progression in a large cohort of oral dysplasia patients.

METHODS: One hundred forty eight oral dysplasia cases underwent immunohistochemical analysis using a monoclonal antibody against p16(INK4a) . Clinical factors were also collated on each case. Slides were double scored independently by two trained observers. Univariate analyses using both logistic and Cox regression models were performed.

RESULTS: Thirty nine of 148 cases progressed to cancer. Ten of 148 cases (7%) were p16(INK4a) positive. High grade of dysplasia (P = 0.0002) and lesion morphology (P = 0.03) were found to be prognostic of malignant progression. p16(INK4a) score was not prognostic in this cohort (P = 0.29). This did not change with a time to event analysis (P = 0.24).

CONCLUSION: Few studies have assessed the aetiological role of HPV in cancer development from dysplastic lesions. Our study, using one of the largest cohorts of oral dysplasia, demonstrated a low rate of p16(INK4a) positivity and was unable to confirm a prognostic ability for this biomarker.

Bibliographic note

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Details

Original languageEnglish
Pages (from-to)245-9
Number of pages5
JournalJournal of Oral Pathology and Medicine
Volume43
Issue number4
Early online date26 Dec 2013
Publication statusPublished - Apr 2014

Keywords

  • Alphapapillomavirus, Antibodies, Monoclonal, Biological Markers, Carcinoma in Situ, Carcinoma, Squamous Cell, Cell Transformation, Neoplastic, Cohort Studies, Cyclin-Dependent Kinase Inhibitor p16, Epithelial Cells, Female, Follow-Up Studies, Humans, Immunohistochemistry, Male, Middle Aged, Mouth Mucosa, Mouth Neoplasms, Papillomavirus Infections, Precancerous Conditions, Prognosis