Specific oral microbial shifts associated with the transition from healthy mucosa to oral dysplasia
Oral potentially malignant disorders (OPMDs) are a group of conditions that carry a risk of oral squamous cell carcinoma (OSCC) development. The presence and grade of epithelial dysplasia is currently the gold standard in determining the risk of progression to OSCC. Recent studies indicate that periodontal disease–associated pathogenic bacteria may play a role in the transition from healthy mucosa to dysplasia and to OSCC. Although the oral microbiome and its dysbiosis have been implicated in the pathogenesis of oral cancer, the microbial signatures associated with the transition from healthy mucosa to dysplasia to carcinogenesis have not been established. To characterize oral microbial signatures during this transition, we performed 16S sequencing and analysed both oral swab and formalin-fixed, paraffin-embedded tissue (FFPE) samples. We collected oral swabs from healthy mucosa (from healthy patients), normal mucosa adjacent to dysplasia, and low-grade oral dysplasia. We also collected FFPE samples from normal mucosa adjacent to OSCC, plus low grade and high-grade oral dysplasia samples. Our data demonstrate significant differences in the alpha and beta microbial diversities during the transition from health to dysplasia and to OSCC, as well as increased dissimilarities among these transitions. We found that the Proteobacteria phyla abundance increased, concurrent with a progressive decrease in the Firmicutes phyla abundance in the transition from health to disease. Additionally, Fusobacteria tended to increase in the transition from health to carcinogenesis. Moreover, we found in swab samples that the oral microbiome may be altered in areas that appear to be normal, including in mucosa that are histologically normal adjacent to dysplasia. In addition, trends in specific microbiome changes in oral swab samples preceded those in the tissues; signifying early detection opportunities for clinical diagnosis. These findings suggest that features of the oral microbiome can serve as novel biomarkers for OSCC disease progression.