Periodontal inflammation as a negative stimulus for oral cancerization: the hidden role of periodontitis in oral cancerization

Periodontal inflammation, a hallmark of periodontitis, has well-known detrimental effects on oral health. Emerging evidence suggests it may also contribute to the development of oral squamous cell carcinoma (OSCC) as well as the progression of oral potentially malignant disorders (OPMDs). Chronic periodontal inflammation may contribute to oncogenesis through multiple mechanisms. The underlying biology involves the inflammatory cytokines production, immune cell infiltration, oxidative stress, and their impact on cellular behavior. Furthermore, low-grade systemic inflammation emerging from microbial dysbiosis may promote cancer cell survival, proliferation, and immune evasion – key processes in carcinogenesis. The interaction between periodontal pathogens and host tissues is closely intertwined with the progression toward epithelial dysplasia, epithelial–mesenchymal transition (EMT), and neoangiogenesis. While most of the evidence supports the association between OSCC and periodontitis, the limitations of these studies, the presence of confounding factors, and conflicting findings call this relationship into question. In this context, this review aims to discuss the most recent evidence regarding the link between periodontitis and oral carcinogenesis, with a particular focus on the ecological and molecular mechanisms underlying epithelial dysplasia, tumor initiation, progression and metastasis, while also providing new perspectives for its prevention and treatment.