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Periodontitis and Oral and Oropharyngeal Cancer Risk: A Systematic Review and Meta-Analysis with Exploratory Evidence on Tumor-Associated Porphyromonas gingivalis

Abstract:

Background: Periodontitis is a chronic inflammatory condition characterized by progressive destruction of tooth-supporting tissues and sustained microbial dysbiosis. Increasing evidence suggests that chronic oral inflammation may be associated with oral and oropharyngeal carcinogenesis, although findings across epidemiological and prognostic studies remain heterogeneous. Objective: To systematically evaluate the epidemiological association between clinically defined periodontitis and the risk of oral and/or oropharyngeal cancer, and to explore, in a distinct analytical component, the prognostic association between tumor-associated periodontal pathogens, particularly Porphyromonas gingivalis, and survival outcomes in affected patients. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines and registered in PROSPERO (CRD420251273975). Observational studies evaluating periodontitis and oral/oropharyngeal cancer risk (Arm 1) and prognostic studies assessing tumor-associated periodontal pathogens and survival outcomes (Arm 2) were identified through comprehensive database searches. Random-effects meta-analyses were performed to pool adjusted effect estimates. Risk of bias was assessed using the Newcastle–Ottawa Scale and the QUIPS tool. Results: Six observational studies were included in the epidemiological meta-analysis. Periodontitis was significantly associated with an increased risk of oral and/or oropharyngeal cancer (pooled HR = 2.14; 95% CI: 1.53–2.98), with substantial heterogeneity; trial sequential analysis supported the statistical robustness of this association. In the separate prognostic analysis, three studies evaluating intratumoral Porphyromonas gingivalis were included. A higher presence or expression of P. gingivalis was associated with poorer overall survival (HR = 2.89; 95% CI: 1.93–4.32), with no observed heterogeneity. Sensitivity and influence analyses confirmed the stability of these findings. Conclusions: This systematic review and meta-analysis demonstrate a consistent epidemiological association between periodontitis and an increased risk of oral and/or oropharyngeal cancer. In addition, exploratory prognostic evidence suggests that the presence of Porphyromonas gingivalis within tumor tissue may be associated with adverse survival outcomes. These findings should be interpreted as addressing distinct clinical and microbiological constructs, underscoring the need for further well-designed prospective and mechanistic studies.