Oral squamous cell carcinoma (OSCC) accounts for 90% of oral cancers. According to the National Cancer Registry, the rate of OSCC in Ireland is increasing annually by 3.3%. OSCCs can arise de novo or from preneoplasis such as Oral Leukoplakia (OLK). Risks factors for OLK include smoking and alcohol consumption, however the mechanisms by which OLK progresses to OSCC are poorly understood and it is difficult to predict which OLKs will resolve or progress. The degree of dysplasia on biopsy is the best indicator of progression, with severe dysplasia being associated with greater risk relative to mild or moderate dysplasia. Recently, oral bacteria such as Fusobacterium nucleatum have been identified as potential drivers of malignant progression in the GI tract. Our recently published preliminary data examining the microbiome of OLK has shown that OLK lesions are colonised with a greater abundance of Fusobacteria, Campylobacter species and Candida albicans compared to healthy mucosa from the same patient. Our hypothesis is that changes in the composition of the mucosal microbiome are a driver of the malignant transformation of oral leukoplakia (OLK) to oral squamous cell carcinoma (OSCC). Characterisation of these microbiome changes will allow us to identify the organisms associated with severe dysplasia and therefore develop tests to identify the patients at greatest risk of malignant progression. In this study we will carry out a comprehensive comparison of the OLK microbiome compared to the healthy mucosal microbiome by Illumina sequence analysis in a large cohort of patients (n=235) to determine whether colonisation of OLK with certain microorganisms is significantly associated with severe dysplasia. These data will indicate whether routine microbiome profiling could be useful as a tool to predict the risk of malignant progression and whether topical antibiotic therapy is warranted to reduce the risk of OSCC.
