Oral Microbial Dysbiosis Driven by Periodontitis Facilitates Oral Squamous Cell Carcinoma Progression

Background: Oral squamous cell carcinoma (OSCC), which accounts for over 90% of all oral malignancies, remains a major global health challenge due to its aggressive clinical course and poor prognosis. Periodontitis, a widespread chronic inflammatory condition affecting the supporting structures of the teeth, has increasingly been implicated as a potential risk factor for the development of various cancers. Emerging evidence suggests that microbial dysbiosis within the oral cavity may contribute to the creation of a pro-tumorigenic microenvironment, thereby promoting tumor initiation and progression. Nevertheless, the precise mechanisms linking periodontitis to OSCC, particularly through alterations in the oral microbiota, remain insufficiently understood. This article seeks to comprehensively analyze the association between periodontitis and OSCC and to elucidate the potential role of oral microbiota dysbiosis in mediating this relationship. Methods: In this study, a ligature-induced periodontitis model was established in C57BL/6J mice, and after two weeks, an OSCC model was introduced by the subcutaneous injection of SCC-7 cells to investigate the impact of periodontitis on OSCC progression. The effects of periodontitis on OSCC cell proliferation and invasion were assessed using scratch wound healing assays and CCK-8 proliferation assays. 16S rDNA high-throughput sequencing was conducted to profile the microbial communities present in the oral cavity and OSCC tissues, with particular emphasis on α-diversity indices (including Pielou’s evenness and Chao1 richness) and taxonomic composition at both the phylum and class levels. Furthermore, qPCR was utilized to assess the expression levels of cytokines in both periodontal and OSCC tissues, thereby elucidating the inflammatory milieu, potentially linking periodontitis to OSCC progression. Results: Our findings demonstrated that periodontitis significantly promoted OSCC growth and enhanced the invasive potential of OSCC cells. Microbial profiling revealed marked alterations in both the oral and OSCC microbiota, characterized by significant shifts in community composition and increased microbial diversity. Notably, these microbial changes exhibited consistent patterns between the oral cavity and the OSCC microenvironment, suggesting a potential mechanistic link between periodontitis-associated dysbiosis and OSCC progression. Consistently, qPCR analysis revealed elevated expression levels of IL-1β, IL-10, and IL-18 in both periodontal and OSCC tissues, providing evidence that the microbial alterations were accompanied by intensified inflammatory responses, which may contribute to OSCC progression. Conclusions: This study underscores the intricate interplay between periodontitis-induced microbial dysbiosis and the development of oral squamous cell carcinoma (OSCC). The findings suggest that periodontal inflammation, together with associated shifts in the oral microbiota, acts synergistically to drive OSCC progression. The elevated expression of cytokines further supports the role of a pro-inflammatory tumor microenvironment in mediating this interaction. These results offer important insights into the microbial and inflammatory mechanisms underlying the connection between periodontitis and OSCC, highlighting the critical role of maintaining periodontal health in the prevention and management of OSCC.