P32 Prospective study on human papillomavirus significance in oral dysplasias in association with clinical parameters and P16INK4a expression

Abstract

Human papillomavirus (HPV) DNA and RNA is found in a subset of oral cavity squamous cell carcinomas (OSCC), indicating a transforming role of the virus in a proportion of those cancers. HPV DNA has also been detected in some oral premalignant lesions (OPL). However, the significance of HPV DNA detection in those lesions is currently unclear. In particular, the association with clinical parameters, p16INK4a and progression risk has not been analyzed in a prospective cohort yet. Formalin-fixed, paraffin-embedded biopsies of mild, moderate and severe OPL deriving from the “Oral Cancer Prediction Longitudinal study” (OCPL), British Columbia, Canada, were analyzed for HPV DNA, genotype and semi-quantitative viral load applying Luminex technology. The results were correlated to various clinical parameters including time to progression and p16INK4a immunohistochemical expression as a potential surrogate marker of HPV-induced transformation in those lesions. Thirteen out of 149 (8.7%) samples were HPV DNA-positive (high risk (HR)-HPV16: 7/13, HR-HPV18: 6/13) with a low mean “median fluorescence intensity (MFI)” as a semi-quantitative measure of viral load (204.6 and 186.8 MFI, respectively). HPV DNA-positivity was associated with higher lesion progression risk (p = 0.038). Half of the 149 samples demonstrated focal p16INK4a expression (52%), 13% showed a diffuse pattern and 35% were p16INK4a-negative. Staining patterns did not differ by age, gender, ethnicity or smoking habit (ever vs never smoker); however, current smokers more often showed p16INK4a overexpression (37% focal, 42% diffuse, 17% negative; p = 0.02). Progression occurred in 7 lesions: 0/78 focal, 6/52 negative and 1/19 diffuse p16INK4a expression (p = 0.01). No significant association between HPV DNA-positivity and p16INK4a expression was observed. Our results demonstrate a higher progression risk in HPV DNA-positive OPL patients. HPV DNA-positivity in those lesions might represent a non-transforming bystander infection, particularly considering the comparatively low MFIs and the lacking association with p16INK4a expression. Assessment of HR-HPV oncogene transcription in the HPV DNA-positive OPL will be performed to differentiate truly HPV-transformed lesions from potential bystander infections. OPL with focal p16INK4a expression appear to have a low likelihood of progression independent of HPV DNA status.