Abstract 5306: p16INH4a status helps predict clinical outcome of dysplasia in the oral cavity irrespective of HPV status

Objectives: p16INK4a is a key gatekeeper for multiple biological processes that are associated with protection from cancer, including cell cycle control and senescence. Elevated expression of this gene is strongly correlated with biological activity of HPV infection and cancer development in uterine cervix and tonsil. Although HPV DNA has been found in a small portion of oral cavity cancers and dysplasia, the relevance of its presence to cancer development at this site is unclear, as is the significance of an expression change in p16INK4a as a predictor of HPV status, tissue behavior and outcome. Methods: Formalin-fixed, paraffin-embedded biopsies from 164 patients with mild, moderate and severe oral dysplasia in the “Oral Cancer Prediction Longitudinal study” (OCPL), British Columbia, Canada, were analyzed for HPV DNA using a semi-quantitative viral load Luminex technology. Expression of p16INK4a was assessed and categorized into 3 staining patterns (diffuse, focal, and negative). Results: HPV DNA was found in 13 (8%) lesions, 7 had HPV-16 infection and 1 HPV-18. Of the 164 samples, diffuse p16INK4a expression was present in 18%, focal in 56% and no p16 staining in 23% of samples. There was no significant correlation between HPV DNA-positivity and p16INK4a staining. Different p16 staining patterns showed significantly different progression rates (P < 0.0001): progression occurred in 1/92 (1.1%) focally stained, 1/29 (3.5%) diffusely stained and 10/43 (23.3%) with no staining. Conclusion: HPV DNA-positivity occurs in a small proportion of oral dysplasia but is poorly associated with p16INK4a expression. Future assessment of these samples for HR-HPV oncogene transcripts will provide information on its biological activity. The low likelihood of progression of p16INK4a focally stained lesions suggests a value of this marker in identification of low-risk cases. Acknowledgements: Supported by Else Kröner-Fresenius-Stiftung Foundation, Germany Citation Format: Tarinee Lubpairee, Elena Prigge, Magnus von Knebel Doeberitz, Miriam Reuschenbach, Lewei Zhang, Miriam P. Rosin. p16INH4a status helps predict clinical outcome of dysplasia in the oral cavity irrespective of HPV status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5306. doi:10.1158/1538-7445.AM2017-5306