Accuracy of Cytological Methods in Early Detection of Oral Squamous Cell Carcinoma and Potentially Malignant Disorders: A Systematic Review and Meta‐Analysis

Abstract

Introduction: Oral squamous cell carcinoma (OSCC) carries significant global mortality rates. Brush cytology presents a potential adjunctive tool for early detection and monitoring of OSCC and oral potentially malignant disorders (OPMDs). This study aims to systematically evaluate the diagnostic accuracy of cytology for detecting OSCC and OPMDs compared to histopathology as the reference standard. We conducted a systematic review and meta-analysis following PRISMA-DTA guidelines. Material and methods: We searched PubMed, Embase, Scopus, Cochrane Library, and Web of Science from inception to January 2023 (updated in March 2025). Eligible studies included cohort studies evaluating cytology versus histopathological diagnosis. Two reviewers independently screened studies, extracted data, and assessed risk of bias using QUADAS-2. We used the Hierarchical Summary Receiver Operating Characteristic model for meta-analysis. Results: Of 2603 identified studies, 53 met inclusion criteria, comprising 13,249 patients. Cytology demonstrated a pooled sensitivity of 0.914 (95% CI: 0.878-0.941) and specificity of 0.960 (95% CI: 0.937-0.975). The diagnostic odds ratio was 137.502 (95% CI: 79.733-237.127), with a positive likelihood ratio of 11.970 (95% CI: 9.005-15.912) and negative likelihood ratio of 0.096 (95% CI: 0.059-0.158). Subgroup analysis showed improved performance when exfoliative cytology was combined with DNA analysis or when using a metal spatula. Both conventional and liquid-based cytology were effective, with the latter showing modest advantages. Heterogeneity was substantial across studies (I2 = 86.26%). Conclusion: Cytology demonstrates good diagnostic accuracy for detecting OSCC and OPMDs and may serve as a valuable adjunctive screening tool. However, it does not replace histopathological examination as the diagnostic gold standard. Further research should focus on standardizing collection techniques and interpretation criteria. Registration: PROSPERO CRD42023438610.