Accuracy of Gingival Crevicular Fluid Biomarkers for Oral Cancer Diagnosis: A Systematic Review and Meta-analysis
摘要
Early detection of oral squamous cell carcinoma (OSCC) remains a critical determinant of prognosis. Gingival crevicular fluid (GCF), a site-specific biological fluid reflecting local tissue metabolism, may contain diagnostic biomarkers of malignancy. This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of GCF biomarkers for detecting OSCC. A comprehensive electronic search was conducted across PubMed, Scopus, Web of Science, and Google Scholar up to September 2025 following PRISMA 2020 guidelines. Eligible studies assessed GCF biomarkers in OSCC patients, with histopathology as the reference standard. Data were extracted for sensitivity, specificity, and area under the curve (AUC). Methodological quality was evaluated using QUADAS-2, and pooled diagnostic parameters were estimated using randomeffects models. Three studies involving approximately 390 participants met inclusion criteria. The most frequently investigated biomarkers were matrix metalloproteinases (MMP-1, MMP-8, and MMP-9). The pooled sensitivity was 0.73 (95% CI: 0.12–1.00), specificity 0.75 (95% CI: 0.13–1.00), positive likelihood ratio 2.44, negative likelihood ratio 0.39, and diagnostic odds ratio 7.02, with a summary AUC of 0.76, indicating moderate diagnostic accuracy. Considerable heterogeneity was observed, primarily due to differences in study design, assay type, and periodontal control. GCF biomarkers, particularly MMPs, demonstrate promising but limited diagnostic accuracy for OSCC detection. While biologically plausible and minimally invasive, the current evidence is insufficient for clinical implementation. Larger, prospective, multicentre studies with standardized GCF collection, controlled periodontal variables, and validation of multimarker panels are required to establish GCF as a reliable adjunctive diagnostic tool for early oral cancer detection. Research registration unique identifying number (UIN): PROSPERO Registration number CRD420251165882.