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Association of torque teno virus in periodontitis: a systematic review, meta-analysis, and trial sequential analysis

Abstract:

Background: Periodontitis, affecting 38.5% of adults globally with moderate-to-severe forms, represents a multifactorial inflammatory disease traditionally attributed to bacterial pathogens. Emerging evidence implicates viral cofactors, particularly Torque Teno virus (TTV), a ubiquitous anellovirus with 30%–95% prevalence in healthy populations. Objective: To evaluate TTV prevalence in periodontitis patients vs. controls through systematic review and meta-analysis. Methods: Following PRISMA guidelines, we searched multiple databases (2000–2024) for observational studies reporting TTV detection in oral samples using molecular techniques. Random-effects meta-analysis calculated pooled relative risk (RR) with 95% confidence intervals. Trial Sequential Analysis assessed evidence sufficiency. Results: Four studies encompassed 583 participants (300 periodontitis, 283 controls). Meta-analysis revealed significant TTV-periodontitis association (RR = 1.67; 95%CI: 1.28–2.17; p < 0.001), indicating 67% increased TTV likelihood in periodontitis patients. Heterogeneity was minimal (I<sup>2</sup> = 0%) with no publication bias detected. Trial Sequential Analysis showed current evidence represents only 31.6% of required information size (1,847 participants), suggesting preliminary findings requiring validation. Conclusion: Despite consistent TTV-periodontitis association across studies, evidence remains insufficient for definitive conclusions. Larger prospective investigations using standardized diagnostic criteria are essential to establish causality and clinical significance. Systematic Review Registration: PROSPERO CRD420251127439.