Systematic review finds serum biomarkers show variable diagnostic accuracy for oral cancer detection
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Key Takeaway
Consider serum biomarkers as potential adjuncts for OSCC detection, but interpret with caution due to variable accuracy and study bias.
This systematic review and meta-analysis evaluated the diagnostic accuracy of various serum biomarkers for oral squamous cell carcinoma (OSCC). The analysis included data from 3,309 subjects (2,069 with OSCC and 1,240 controls) and examined biomarkers including CYFRA 21-1, E-cadherin, interleukins (IL-6, IL-8), protein peaks, matrix metalloproteinases (MMP-9), vascular endothelial growth factor (VEGF), galectins (1, 3), and various RNA biomarkers compared to controls.
Diagnostic performance varied substantially across biomarkers. Overall sensitivity ranged from 16% to 94% and specificity from 37% to 100%. IL-8 demonstrated the highest accuracy with mean sensitivity of 86.5% and specificity of 98%. CYFRA 21-1 showed an area under the curve (AUC) of 0.53. Safety and tolerability data were not reported in the included studies.
Key limitations include moderate to high risk of bias in the included studies, which affects the reliability of the pooled estimates. Funding sources and conflicts of interest were not reported. The review suggests serum biomarkers have potential as adjunctive diagnostic tools that could complement histopathology and improve early detection, particularly in screening contexts. However, the substantial variability in performance and methodological limitations of the underlying evidence mean these findings should be interpreted cautiously in clinical practice.
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View Original Abstract ↓
AIM: Evaluating Diagnostic Ability Of Various Serum Biomarkers For Oral Cancer (OSCC).
METHODS: Review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Diagnostic Test Accuracy (PRISMA-DTA) checklist, and the review protocol was registered under PROSPERO (CRD42024625802). Databases were searched from January 2000 to December 2024 to identify the diagnostic potential of various serum biomarkers. Quality assessment was evaluated based on the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool, and meta-analysis was performed in Meta-Disc 1.4 software and Review Manager 5.3 for pooled sensitivity, specificity, positive likelihood ratio (+PLR), negative likelihood ratio (-NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves.
RESULTS: Twenty-three studies were included in the review, with data evaluated from 3,309 subjects (diseased - 2,069 and 1,240 - controls). The included studies showed a moderate to high risk of bias. Various biomarkers such as CYFRA 21-1, E-cadherin, interleukins (IL-6, IL-8), protein peaks, matrix metalloproteinases (MMP-9), vascular endothelial growth factor (VEGF), galectins (1, 3), and various RNA biomarkers were evaluated, belonging to the protein and microRNA classes of biomarkers. It was found that these biomarkers had sensitivity and specificity ranging from 16% to 94% and 37% to 100%, respectively, with the highest accuracy shown by IL-8, which had a mean sensitivity and specificity of 86.5% and 98%. The highest AUC was observed for CYFRA 21-1 (0.53), suggesting that the overall diagnostic accuracy of these serum biomarkers is moderate to good in diagnosing the desired condition.
CONCLUSION: Serum biomarkers are a valid tool and, overall, have good diagnostic potential in identifying the target condition. They can be used as an alternative adjunct to histopathology. Serum biomarkers also have significant potential in predicting and diagnosing disease outcomes, and they can improve the quality and reach of early screening and detection of OSCC. Serum biomarkers can be employed for early diagnosis and prompt treatment under the secondary level of prevention.
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