Grading the evidence for the association between periodontal disease and chronic non-communicable diseases: an umbrella review of meta-analyses of observational studies

Substantial but inconsistent evidence has implicated periodontal disease (PD) as a potential risk factor for multiple chronic non-communicable diseases (NCDs), but the overall quality and credibility of this evidence have not been systematically evaluated and quantified in aggregate. We thus systematically assessed the associations between PD and the risk of chronic NCDs. Following PRISMA guidelines, we searched PubMed, Embase, Cochrane, and Web of Science for meta-analyses of observational studies. Methodological quality was assessed with AMSTAR 2. Summary effects were recalculated using random-effects models, with heterogeneity and bias evaluated via I 2 statistics, 95% prediction intervals, and Egger's and excess significance tests. Evidence was graded into five credibility levels. Thirty-eight meta-analyses with 58 associations across nine disease categories were included. Eighty-one percent of associations were significant ( P < 0.05), and 25.9% remained significant at P < 10⁻⁶. However, only 11 associations (18.9%) had 95% prediction intervals excluding the null value, indicating limited robustness and substantial between-study heterogeneity for most associations. Four associations (6.9%) provided highly suggestive evidence (Class II), namely Helicobacter pylori infection, urogenital cancer, total cancer, and oral cancer. Three of these four Class II associations had 95% prediction intervals excluding the null value, whereas total cancer did not (95% PI, 0.98–1.32). None of the four Class II associations was supported by a representative meta-analysis rated as high quality by AMSTAR 2. In exploratory subgroup analysis, the oral cancer association weakened and was downgraded from Class II to Class IV when restricted to objective clinical/radiographic PD definitions. Methodological quality was limited, with 26 of 38 included meta-analyses (68.4%) rated as low or critically low quality. The overall evidence base should be interpreted cautiously. This umbrella review found statistically highly suggestive evidence linking PD to an increased risk of a limited number of chronic NCDs, namely Helicobacter pylori infection, urogenital cancer, total cancer, and oral cancer. However, total cancer did not have a 95% prediction interval excluding the null value, and none of the four Class II associations was supported by a high-quality representative meta-analysis; moreover, the oral cancer association weakened and was downgraded to Class IV under objective clinical/radiographic PD definitions. These findings should therefore be interpreted cautiously, and PD should be regarded as a statistically associated factor across a limited set of chronic NCDs, with insufficient evidence to support causal or modifiable interpretation. PROSPERO CRD420251009702.