Abstract

Abstract Background: Bacterial and virus infection may cause pre-malignant and malignant disorder such as hepatocellular carcinoma and cervical cancer. Recent studies reported that oral bacterium is associated with gastric and colon cancer. However, it is not clear yet if the oral microbiome affects the development of pre-malignant disorder in oral cavity and oral cancer. Thus, this study aims to identify the periodontal pathogen candidates involved in the onset and progression of oral squamous cell carcinoma (OSCC). Materials and Methods: Saliva was collected from 112 patients without oral mucosal diseases (OMDs) as control, 36 patients with oral potentially malignant disorders (OPMDs), and 104 patients with OSCC, and DNA was extracted in each sample. Periodontal examinations were performed on all patients. Endpoint-PCR was performed on seven species of oral pathogens using the extracted DNA. 16S ribosomal RNA (rRNA) was utilized for analysis of oral microbiome with 20 samples in each group. 4-nitroqquinoline-1-oxide (4-NQO)-induced tongue tumor model in mice was analyzed with or without endotoxin of one of the oral bacteria, Porphyromonas gingivalis (P. gingivalis). Results: From the statistical analysis of the clinical parameters, periodontal disease tended to worsen in the OMPD and OSCC groups compared to the control group. The number of oral bacteria was significantly higher in the OSCC group than those in other groups. From PCR results, the detection rates of P. gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola were significantly higher in the OSCC group than those in the control group. From 16S rRNA analysis, the relative abundance of Prevotella buccae and intermedia was significantly higher in OSCC groups than in the control group. Furthermore, the relative abundance of P. gingivalis was higher in the OSCC group compared to other groups, regardless of age and the number of teeth. In mouse model, mice treated with P. gingivalis-derived endotoxin developed oral leukoplakia at earlier time points and tumors significantly higher lesions compared to control group. Conclusion: These results suggest that specific periodontal pathogens are present in the oral cavity of OPMDs and OSCC patients and those changes in the bacterial flora due to their presence may contribute to the onset and progression of OMDs. Citation Format: Mitomu Kioi, Hiroshi Isono, Shintaro Nakajima. Specific oral microbiome is closely associated with oral potentially malignant disorders and oral squamous cell carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4238.

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