Blanco Pintos, TrianaRegueira Iglesias, AlbaSeijo Porto, IriaBalsa Castro, CarlosCastelo Baz, PabloNibali, LuigiTomás Carmona, Inmaculada2023-11-072023-11-072023-08-22Journal of Clinical Periodontology, 2023 50(11), 1420–14430303-6979http://hdl.handle.net/10347/31189Aim To determine the accuracy of biomarker combinations in gingival crevicular fluid (GCF) and saliva through meta-analysis to diagnose periodontitis in systemically healthy subjects. Methods Studies on combining two or more biomarkers providing a binary classification table, sensitivity/specificity values or group sizes in subjects diagnosed with periodontitis were included. The search was performed in August 2022 through PUBMED, EMBASE, Cochrane, LILACS, SCOPUS and Web of Science. The methodological quality of the articles selected was evaluated using the QUADAS-2 checklist. Hierarchical summary receiver operating characteristic modelling was employed to perform the meta-analyses (CRD42020175021). Results Twenty-one combinations in GCF and 47 in saliva were evaluated. Meta-analyses were possible for six salivary combinations (median sensitivity/specificity values): IL-6 with MMP-8 (86.2%/80.5%); IL-1β with IL-6 (83.0%/83.7%); IL-1β with MMP-8 (82.7%/80.8%); MIP-1α with MMP-8 (71.0%/75.6%); IL-1β, IL-6 and MMP-8 (81.8%/84.3%); and IL-1β, IL-6, MIP-1α and MMP-8 (76.6%/79.7%). Conclusions Two-biomarker combinations in oral fluids show high diagnostic accuracy for periodontitis, which is not substantially improved by incorporating more biomarkers. In saliva, the dual combinations of IL-1β, IL-6 and MMP-8 have an excellent ability to detect periodontitis and a good capacity to detect non-periodontitis. Because of the limited number of biomarker combinations evaluated, further research is required to corroborate these observationseng© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposesAtribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/Diagnostic accuracyMeta-analysisMolecular biomarkersOral fluidsPeriodontitisjournal article10.1111/jcpe.138541600-051Xopen access