Non-Cochrane · DTA · PM41945936
Diagnostic Efficacy of Serum Biomarkers for Oral Cancer: An Updated Systematic Review and Meta-Analysis.
Anusikha Anuja, Chinnannavar Sangamesh N, Mishra Silpiranjan, et al. · Asian Pacific journal of cancer prevention : APJCP · 2026 · PubMed · doi:10.31557/apjcp.2026.27.4.1189
Findings
Population Patients with oral squamous cell carcinoma and controls
79 findings
| Serum CYFRA 21-1 (index test) | Biopsy with histopathology (reference standard) | Specificity | Specificity 0.42 [0.03, 0.91] GRADE not reported 4 studies |
| Serum CYFRA 21-1 (index test) | Biopsy with histopathology (reference standard) | Negative likelihood ratio | Negative likelihood ratio 1.33 [0.41, 4.26] GRADE not reported 4 studies |
| Serum CYFRA 21-1 (index test) | Biopsy with histopathology (reference standard) | Sensitivity | Sensitivity 0.37 [0.03, 0.87] GRADE not reported 4 studies |
| Serum CYFRA 21-1 (index test) | Biopsy with histopathology (reference standard) | Area under the SROC curve | AUC 0.33 GRADE not reported 4 studies |
| Serum CYFRA 21-1 (index test) | Biopsy with histopathology (reference standard) | Mean sensitivity (unweighted average of study values) | Mean sensitivity (%) 60.5 GRADE not reported 4 studies |
| Serum CYFRA 21-1 (index test) | Biopsy with histopathology (reference standard) | Mean specificity (unweighted average of study values) | Mean specificity (%) 93.5 GRADE not reported 4 studies |
| Serum CYFRA 21-1 (index test) | Biopsy with histopathology (reference standard) | Positive likelihood ratio | Positive likelihood ratio 0.65 [0.16, 2.53] GRADE not reported 4 studies |
| Serum CYFRA 21-1 (index test) | Biopsy with histopathology (reference standard) | Diagnostic odds ratio | Diagnostic odds ratio 0.36 [0.01, 9.26] GRADE not reported 4 studies |
| Serum E-cadherin (index test) | Biopsy with histopathology (reference standard) | Mean specificity (unweighted average of study values) | Mean specificity (%) 71 GRADE not reported 2 studies |
| Serum E-cadherin (index test) | Biopsy with histopathology (reference standard) | Specificity | Specificity 0.14 [0.01, 0.98] GRADE not reported 2 studies |
| Serum E-cadherin (index test) | Biopsy with histopathology (reference standard) | Sensitivity | Sensitivity 0.46 [0.01, 0.98] GRADE not reported 2 studies |
| Serum E-cadherin (index test) | Biopsy with histopathology (reference standard) | Positive likelihood ratio | Positive likelihood ratio 0.53 [0.10, 2.81] GRADE not reported 2 studies |
| Serum E-cadherin (index test) | Biopsy with histopathology (reference standard) | Mean sensitivity (unweighted average of study values) | Mean sensitivity (%) 56 GRADE not reported 2 studies |
| Serum E-cadherin (index test) | Biopsy with histopathology (reference standard) | Diagnostic odds ratio | Diagnostic odds ratio 0.14 [0.00, 52.20] GRADE not reported 2 studies |
| Serum E-cadherin (index test) | Biopsy with histopathology (reference standard) | Negative likelihood ratio | Negative likelihood ratio 3.93 [0.03, 441.65] GRADE not reported 2 studies |
| Serum Protein peaks (index test) | Biopsy with histopathology (reference standard) | Mean sensitivity (unweighted average of study values) | Mean sensitivity (%) 80.3 GRADE not reported 3 studies |
| Serum Protein peaks (index test) | Biopsy with histopathology (reference standard) | Negative likelihood ratio | Negative likelihood ratio 1.55 [0.16, 14.83] GRADE not reported 3 studies |
| Serum Protein peaks (index test) | Biopsy with histopathology (reference standard) | Positive likelihood ratio | Positive likelihood ratio 0.75 [0.18, 3.15] GRADE not reported 3 studies |
| Serum Protein peaks (index test) | Biopsy with histopathology (reference standard) | Sensitivity | Sensitivity 0.46 [0.03, 0.95] GRADE not reported 3 studies |
| Serum Protein peaks (index test) | Biopsy with histopathology (reference standard) | Diagnostic odds ratio | Diagnostic odds ratio 0.44 [0.01, 22.55] GRADE not reported 3 studies |
| Serum Protein peaks (index test) | Biopsy with histopathology (reference standard) | Mean specificity (unweighted average of study values) | Mean specificity (%) 77 GRADE not reported 3 studies |
| Serum Protein peaks (index test) | Biopsy with histopathology (reference standard) | Specificity | Specificity 0.31 [0.00, 0.96] GRADE not reported 3 studies |
| Serum MMP-2 (index test) | Biopsy with histopathology (reference standard) | Sensitivity | Sensitivity 0.31 [0.00, 0.98] GRADE not reported 2 studies |
| Serum MMP-2 (index test) | Biopsy with histopathology (reference standard) | Mean specificity (unweighted average of study values) | Mean specificity (%) 67 GRADE not reported 2 studies |
| Serum MMP-2 (index test) | Biopsy with histopathology (reference standard) | Specificity | Specificity 0.25 [0.00, 0.97] GRADE not reported 2 studies |
| Serum MMP-2 (index test) | Biopsy with histopathology (reference standard) | Negative likelihood ratio | Negative likelihood ratio 2.18 [0.14, 34.28] GRADE not reported 2 studies |
| Serum MMP-2 (index test) | Biopsy with histopathology (reference standard) | Mean sensitivity (unweighted average of study values) | Mean sensitivity (%) 32.5 GRADE not reported 2 studies |
| Serum MMP-2 (index test) | Biopsy with histopathology (reference standard) | Positive likelihood ratio | Positive likelihood ratio 0.37 [0.04, 3.84] GRADE not reported 2 studies |
| Serum MMP-2 (index test) | Biopsy with histopathology (reference standard) | Diagnostic odds ratio | Diagnostic odds ratio 0.10 [0.00, 210.08] GRADE not reported 2 studies |
| Serum MMP-9 (index test) | Biopsy with histopathology (reference standard) | Sensitivity | Sensitivity 0.30 [0.00, 0.89] GRADE not reported 3 studies |
| Serum MMP-9 (index test) | Biopsy with histopathology (reference standard) | Negative likelihood ratio | Negative likelihood ratio 2.39 [0.26, 21.98] GRADE not reported 3 studies |
| Serum MMP-9 (index test) | Biopsy with histopathology (reference standard) | Positive likelihood ratio | Positive likelihood ratio 0.43 [0.06, 2.92] GRADE not reported 3 studies |
| Serum MMP-9 (index test) | Biopsy with histopathology (reference standard) | Mean sensitivity (unweighted average of study values) | Mean sensitivity (%) 50 GRADE not reported 3 studies |
| Serum MMP-9 (index test) | Biopsy with histopathology (reference standard) | Area under the SROC curve | AUC 0.53 GRADE not reported 3 studies |
| Serum MMP-9 (index test) | Biopsy with histopathology (reference standard) | Mean specificity (unweighted average of study values) | Mean specificity (%) 74.67 GRADE not reported 3 studies |
| Serum MMP-9 (index test) | Biopsy with histopathology (reference standard) | Specificity | Specificity 0.26 [0.00, 0.90] GRADE not reported 3 studies |
| Serum MMP-9 (index test) | Biopsy with histopathology (reference standard) | Diagnostic odds ratio | Diagnostic odds ratio 0.63 [0.08, 5.20] GRADE not reported 3 studies |
| Serum VEGF (index test) | Biopsy with histopathology (reference standard) | Mean sensitivity (unweighted average of study values) | Mean sensitivity (%) 76 GRADE not reported 3 studies |
| Serum VEGF (index test) | Biopsy with histopathology (reference standard) | Positive likelihood ratio | Positive likelihood ratio 0.81 [0.21, 3.14] GRADE not reported 3 studies |
| Serum VEGF (index test) | Biopsy with histopathology (reference standard) | Diagnostic odds ratio | Diagnostic odds ratio 0.58 [0.02, 20.48] GRADE not reported 3 studies |
| Serum VEGF (index test) | Biopsy with histopathology (reference standard) | Mean specificity (unweighted average of study values) | Mean specificity (%) 88.33 GRADE not reported 3 studies |
| Serum VEGF (index test) | Biopsy with histopathology (reference standard) | Specificity | Specificity 0.32 [0.00, 0.93] GRADE not reported 3 studies |
| Serum VEGF (index test) | Biopsy with histopathology (reference standard) | Negative likelihood ratio | Negative likelihood ratio 1.38 [0.15, 12.74] GRADE not reported 3 studies |
| Serum VEGF (index test) | Biopsy with histopathology (reference standard) | Sensitivity | Sensitivity 0.54 [0.05, 0.97] GRADE not reported 3 studies |
| Serum Galectin-1 (index test) | Biopsy with histopathology (reference standard) | Mean sensitivity (unweighted average of study values) | Mean sensitivity (%) 56 GRADE not reported 2 studies |
| Serum Galectin-1 (index test) | Biopsy with histopathology (reference standard) | Specificity | Specificity 0.26 [0.00, 0.96] GRADE not reported 2 studies |
| Serum Galectin-1 (index test) | Biopsy with histopathology (reference standard) | Diagnostic odds ratio | Diagnostic odds ratio 0.18 [0.00, 22.80] GRADE not reported 2 studies |
| Serum Galectin-1 (index test) | Biopsy with histopathology (reference standard) | Mean specificity (unweighted average of study values) | Mean specificity (%) 80 GRADE not reported 2 studies |
| Serum Galectin-1 (index test) | Biopsy with histopathology (reference standard) | Positive likelihood ratio | Positive likelihood ratio 0.61 [0.08, 4.39] GRADE not reported 2 studies |
| Serum Galectin-1 (index test) | Biopsy with histopathology (reference standard) | Negative likelihood ratio | Negative likelihood ratio 2.55 [0.17, 38.66] GRADE not reported 2 studies |
| Serum Galectin-1 (index test) | Biopsy with histopathology (reference standard) | Sensitivity | Sensitivity 0.37 [0.00, 0.97] GRADE not reported 2 studies |
| Serum Galectin-3 (index test) | Biopsy with histopathology (reference standard) | Mean sensitivity (unweighted average of study values) | Mean sensitivity (%) 63 GRADE not reported 2 studies |
| Serum Galectin-3 (index test) | Biopsy with histopathology (reference standard) | Diagnostic odds ratio | Diagnostic odds ratio 0.21 [0.00, 28.10] GRADE not reported 2 studies |
| Serum Galectin-3 (index test) | Biopsy with histopathology (reference standard) | Positive likelihood ratio | Positive likelihood ratio 0.61 [0.10, 3.89] GRADE not reported 2 studies |
| Serum Galectin-3 (index test) | Biopsy with histopathology (reference standard) | Negative likelihood ratio | Negative likelihood ratio 2.48 [0.10, 62.00] GRADE not reported 2 studies |
| Serum Galectin-3 (index test) | Biopsy with histopathology (reference standard) | Sensitivity | Sensitivity 0.42 [0.01, 0.98] GRADE not reported 2 studies |
| Serum Galectin-3 (index test) | Biopsy with histopathology (reference standard) | Specificity | Specificity 0.23 [0.00, 0.97] GRADE not reported 2 studies |
| Serum Galectin-3 (index test) | Biopsy with histopathology (reference standard) | Mean specificity (unweighted average of study values) | Mean specificity (%) 75 GRADE not reported 2 studies |
| Serum IL-6 (index test) | Biopsy with histopathology (reference standard) | Mean specificity (unweighted average of study values) | Mean specificity (%) 99 GRADE not reported 2 studies |
| Serum IL-6 (index test) | Biopsy with histopathology (reference standard) | Specificity | Specificity 0.51 [0.01, 0.99] GRADE not reported 2 studies |
| Serum IL-6 (index test) | Biopsy with histopathology (reference standard) | Positive likelihood ratio | Positive likelihood ratio 0.81 [0.10, 6.62] GRADE not reported 2 studies |
| Serum IL-6 (index test) | Biopsy with histopathology (reference standard) | Mean sensitivity (unweighted average of study values) | Mean sensitivity (%) 73 GRADE not reported 2 studies |
| Serum IL-6 (index test) | Biopsy with histopathology (reference standard) | Negative likelihood ratio | Negative likelihood ratio 1.24 [0.25, 6.11] GRADE not reported 2 studies |
| Serum IL-6 (index test) | Biopsy with histopathology (reference standard) | Diagnostic odds ratio | Diagnostic odds ratio 0.60 [0.01, 41.30] GRADE not reported 2 studies |
| Serum IL-6 (index test) | Biopsy with histopathology (reference standard) | Sensitivity | Sensitivity 0.38 [0.00, 0.97] GRADE not reported 2 studies |
| Serum IL-8 (index test) | Biopsy with histopathology (reference standard) | Sensitivity | Sensitivity 0.49 [0.01, 0.99] GRADE not reported 2 studies |
| Serum IL-8 (index test) | Biopsy with histopathology (reference standard) | Positive likelihood ratio | Positive likelihood ratio 0.86 [0.13, 5.50] GRADE not reported 2 studies |
| Serum IL-8 (index test) | Biopsy with histopathology (reference standard) | Diagnostic odds ratio | Diagnostic odds ratio 0.71 [0.01, 38.80] GRADE not reported 2 studies |
| Serum IL-8 (index test) | Biopsy with histopathology (reference standard) | Specificity | Specificity 0.43 [0.01, 0.98] GRADE not reported 2 studies |
| Serum IL-8 (index test) | Biopsy with histopathology (reference standard) | Mean sensitivity (unweighted average of study values) | Mean sensitivity (%) 86.5 GRADE not reported 2 studies |
| Serum IL-8 (index test) | Biopsy with histopathology (reference standard) | Negative likelihood ratio | Negative likelihood ratio 1.19 [0.15, 9.46] GRADE not reported 2 studies |
| Serum IL-8 (index test) | Biopsy with histopathology (reference standard) | Mean specificity (unweighted average of study values) | Mean specificity (%) 98 GRADE not reported 2 studies |
| Serum miRNA (index test) | Biopsy with histopathology (reference standard) | Mean sensitivity (unweighted average of study values) | Mean sensitivity (%) 77.75 GRADE not reported 4 studies |
| Serum miRNA (index test) | Biopsy with histopathology (reference standard) | Mean specificity (unweighted average of study values) | Mean specificity (%) 81.5 GRADE not reported 4 studies |
| Serum miRNA (index test) | Biopsy with histopathology (reference standard) | Sensitivity | Sensitivity 0.45 [0.05, 0.91] GRADE not reported 4 studies |
| Serum miRNA (index test) | Biopsy with histopathology (reference standard) | Negative likelihood ratio | Negative likelihood ratio 1.20 [0.23, 6.14] GRADE not reported 4 studies |
| Serum miRNA (index test) | Biopsy with histopathology (reference standard) | Positive likelihood ratio | Positive likelihood ratio 0.81 [0.19, 3.48] GRADE not reported 4 studies |
| Serum miRNA (index test) | Biopsy with histopathology (reference standard) | Diagnostic odds ratio | Diagnostic odds ratio 0.67 [0.03, 16.74] GRADE not reported 4 studies |
| Serum miRNA (index test) | Biopsy with histopathology (reference standard) | Specificity | Specificity 0.44 [0.02, 0.95] GRADE not reported 4 studies |
Included primary studies 20
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Singh 2011 matched by author and year (probable) | NR | 1 other review | Sensitivity | not extracted yet |
| St John 2004 matched by author and year (probable) | NR | 1 other review | Sensitivity | not extracted yet |
| Wang 2014 matched by author and year (probable) | NR | 1 other review | Sensitivity | not extracted yet |
| Aggarwal 2014 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Aggarwal 2015 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Al Kassam 2007 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Ayude 2003 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Ceruse 2005 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Cheng 2005 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Cheng 2008 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Deng 2003 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Gourin 2009 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Karimi 2020 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Linkov 2007 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Malhotra 2012 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Marcos 2009 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Naik 2012 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Rajkumar 2015 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Ries 2014 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
| Saussez 2008 matched by author and year (probable) | NR | this review only | Sensitivity | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Patients with oral cancer (oral squamous cell carcinoma); patients with OPMD/OED or systemic complications excluded | Patients with OSCC and controls (n=3309; 2069 diseased, 1240 controls; 23 studies) |
| Intervention | Serum biomarkers (index test) | Serum biomarkers: CYFRA 21-1 (n=4 studies), E-cadherin (n=2), protein peaks (n=3), MMP-2 (n=2), MMP-9 (n=3), VEGF (n=3), galectin-1 (n=2), galectin-3 (n=2), IL-6 (n=2), IL-8 (n=2), miRNA (n=4) |
| Comparison | Biopsy followed by histopathological investigation (reference standard) | Biopsy followed by histopathological investigation |
| Outcomes | Sensitivity, specificity, AUC, likelihood ratios, diagnostic odds ratio | Pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, AUC (n=21 studies in meta-analysis) |
| Study designs | Cross-sectional and analytical studies; English language, open access, January 2000 to December 2024 | All 23 included studies cross-sectional |
| Timing | Not specified | Not specified |