Cytology adjuncts to determine the need for biopsy for early detection of oral squamous cell carcinoma and potentially malignant disorders: An evidence summary of a living systematic review, Version 2026 1.0

Background: Early detection of oral squamous cell carcinoma and oral potentially malignant disorders can improve survival. Although biopsy remains the diagnostic standard, less invasive adjunctive tests may help determine the need for further evaluation. This living systematic review assesses the impact and diagnostic test accuracy (DTA) of cytology as an adjunct to determine the need for biopsy or referral to detect oral potentially malignant disorders and oral squamous cell carcinoma among adults with or without lesions. Types of Studies Reviewed: The authors updated a 2017 systematic review. The authors conducted searches in MEDLINE, Epistemonikos, Embase, Cochrane Central Register of Controlled Trials through September 3, 2025. Pairs of reviewers independently conducted study selection, data extraction, and assessment of risk of bias. The authors prepared a summary of findings table and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Results: The authors included 36 studies evaluating cytology DTA in adults with lesions. The authors did not identify any randomized trials assessing the impact of cytology on person-important outcomes or studies in adults without lesions. Pooled DTA (7,038 lesions across 35 studies) had a sensitivity of 0.89 (95% CI, 0.83 to 0.92) and a specificity of 0.89 (95% CI, 0.84 to 0.93). The authors rated the certainty of the evidence as low due to risk of bias and indirectness. Cytology produces a large proportion of false-positive results. Conclusions and Practical Implications: Although cytology had acceptable DTA, performance in practice may differ substantially due to serious concerns regarding risk of bias and indirectness of the evidence. When applied to adults with oral lesions, negative cytology may accurately identify healthy patients, reducing unnecessary referrals and biopsies. However, cytology may produce a considerable proportion of false-positive results, leading to unnecessary biopsies and patient anxiety and stress.