Porphyromonas gingivalis-Associated Modulation of β-Catenin Signaling in Oral Squamous Cell Carcinoma: Molecular Perspectives from Periodontal Dysbiosis

TL;DR

This review explores how the bacteria Porphyromonas gingivalis may influence oral cancer through β-catenin signaling, highlighting the need for more research to clarify these connections.

Contribution

The review critically integrates diverse evidence on periodontal dysbiosis and oral cancer, distinguishing between association and causality.

Findings

Population studies show mixed links between periodontitis and oral cancer, often confounded by lifestyle factors.

P. gingivalis can affect β-catenin signaling through noncanonical mechanisms in experimental models.

β-catenin functions as a signaling node in networks influenced by microbial and inflammatory stress.

Abstract

Periodontal disease and oral squamous cell carcinoma (OSCC) are highly prevalent conditions that contribute substantially to global morbidity, as documented by recent Global Burden of Disease analyses. The growing epidemiologic and experimental literature has prompted interest in potential links between chronic periodontal dysbiosis—particularly infection with Porphyromonas gingivalis—and molecular pathways involved in oral carcinogenesis, including β-catenin signaling. This narrative review synthesizes epidemiologic, clinical, and experimental studies examining associations between periodontal disease, P. gingivalis, and OSCC, with focused evaluation of β-catenin as a context-dependent signaling component within broader inflammatory and metabolic networks. Population-based studies report heterogeneous associations between periodontitis and OSCC that are frequently confounded by tobacco use, alcohol consumption, and socioeconomic factors, supporting correlation rather than causal inference. Experimental investigations in vitro and in vivo demonstrate that P. gingivalis can influence β-catenin availability and transcriptional activity through noncanonical mechanisms, including junctional disruption, proteolytic interference with regulatory complexes, and interaction with inflammatory, immune, and metabolic pathways. However, these findings derive largely from simplified model systems and should be interpreted as biologically plausible rather than definitive for human disease. Rather than acting as a dominant oncogenic driver, β-catenin appears to function as an integrative signaling node within a complex network shaped by chronic microbial and inflammatory stress. The principal contribution of this review lies in critically integrating dispersed evidence across study types while explicitly distinguishing association, mechanistic plausibility, and causality. Future longitudinal human studies and mechanistically informed experimental models are required to clarify whether modulation of periodontal dysbiosis or associated signaling pathways has relevance for OSCC risk assessment or prevention.

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