Non-Cochrane · DTA · PM41899572
Diagnostic Accuracy and Clinical Utility of Salivary Biomarkers in Oral Squamous Cell Carcinoma: A Meta-Analysis.
Wijaya Arbi, Julia Vera, Soedarsono Nurtami, et al. · Cancers · 2026 · PubMed · doi:10.3390/cancers18060970
Findings
33 findings
| Population | ||||
|---|---|---|---|---|
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio All studies (before omission of outliers) | Log OR 1.57 [1.2, 1.94] GRADE not reported 45 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Positive likelihood ratio | LR+ 2 GRADE not reported 18 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Detection platform: qRT-PCR | Log OR 1.64 [1.2, 2.09] GRADE not reported 28 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Geographic region: group 2 (unlabeled) | Log OR 1.83 [0.94, 2.73] GRADE not reported 7 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Post-test probability of OSCC after a positive result Pre-test probability 10% · Symptomatic/suspicion lesion clinic · Pre-test probability 10% (Symptomatic/suspicion lesion clinic) | Post-test probability (%) 21 GRADE not reported 18 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Area under the SROC curve | AUC 0.75 [0.71, 0.79] GRADE not reported 18 studies · 1628 participants |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Geographic region: group 3 (unlabeled) | Log OR 2.85 [-1.01, 6.7] GRADE not reported 3 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Post-test probability of OSCC after a negative result Pre-test probability 0.01% · General population screening · Pre-test probability 0.01% (General population screening) | Post-test probability (%) 0 GRADE not reported 18 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Leave-one-out sensitivity: after omission of 9 outlier datasets | Log OR 1.52 [1.23, 1.8] GRADE not reported 36 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Post-test probability of OSCC after a positive result Pre-test probability 0.01% · General population screening · Pre-test probability 0.01% (General population screening) | Post-test probability (%) 0 GRADE not reported 18 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Study quality (QUADAS-2): some concerns | Log OR -0.38 [-1.76, 0.99] GRADE not reported 3 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic odds ratio Random-effects meta-analysis of 45 datasets | DOR 4.53 [3.18, 6.47] GRADE not reported 18 studies · 1628 participants |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Geographic region: group 1 (unlabeled) | Log OR 1.48 [1.09, 1.87] GRADE not reported 33 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Pooled specificity | Specificity 0.71 [0.66, 0.76] GRADE not reported 18 studies · 1628 participants |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Biomarker type: protein based | Log OR 1.59 [0.93, 2.25] GRADE not reported 16 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Detection platform: others | Log OR 1.24 [0.63, 1.86] GRADE not reported 14 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Geographic region: group 4 (unlabeled) | Log OR 2.5 [-5.87, 10.87] GRADE not reported 2 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Study quality (QUADAS-2): high risk | Log OR 1.71 [1.38, 2.05] GRADE not reported 42 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Detection platform: ELISA | Log OR 4.59 [0.44, 8.74] GRADE not reported 3 studies |
| Patients with oral squamous cell carcinoma and healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV miRNAs) | Histopathological confirmation (reference standard) | Threshold effect: correlation of sensitivity and specificity | Correlation coefficient 0.28 GRADE not reported Studies not reported |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Biomarker type: nucleic acid based | Log OR 1.57 [1.12, 2.03] GRADE not reported 29 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Post-test probability of OSCC after a positive result Pre-test probability 0.5% · Low-risk/opportunistic screening · Pre-test probability 0.5% (Low-risk/opportunistic screening) | Post-test probability (%) 1 GRADE not reported 18 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Post-test probability of OSCC after a negative result Pre-test probability 10% · Symptomatic/suspicion lesion clinic · Pre-test probability 10% (Symptomatic/suspicion lesion clinic) | Post-test probability (%) 5 GRADE not reported 18 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Post-test probability of OSCC after a positive result Pre-test probability 40% · High-suspicion/referral setting · Pre-test probability 40% (High-suspicion/referral setting) | Post-test probability (%) 62 GRADE not reported 18 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Post-test probability of OSCC after a negative result Pre-test probability 0.5% · Low-risk/opportunistic screening · Pre-test probability 0.5% (Low-risk/opportunistic screening) | Post-test probability (%) 0 GRADE not reported 18 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic odds ratio Bivariate model (Figure 4 footer) | DOR 4.6 [3.1, 6.83] GRADE not reported 18 studies · 1628 participants |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Pooled sensitivity | Sensitivity 0.64 [0.59, 0.69] GRADE not reported 18 studies · 1628 participants |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Post-test probability of OSCC after a negative result Pre-test probability 40% · High-suspicion/referral setting · Pre-test probability 40% (High-suspicion/referral setting) | Post-test probability (%) 24 GRADE not reported 18 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Pooled sensitivity QUADAS-2 high risk of bias (univariable meta-regression) | Sensitivity 0.82 [0.66, 0.92] GRADE not reported Studies not reported |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Biomarker composition: single biomarker | Log OR 1.56 [1.18, 1.94] GRADE not reported 41 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Diagnostic log odds ratio Biomarker composition: panel biomarker | Log OR 1.67 [-0.0, 3.33] GRADE not reported 4 studies |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Pooled specificity QUADAS-2 high risk of bias (univariable meta-regression) | Specificity 0.91 [0.8, 0.96] GRADE not reported Studies not reported |
| Patients with oral squamous cell carcinoma (OSCC) versus healthy controls | Salivary biomarkers (proteins, cytokines, cfDNA, miRNAs, circRNAs, EV-miRNAs; single or panel) | Histopathological confirmation (reference standard) | Negative likelihood ratio | LR- 0.47 GRADE not reported 18 studies |
Included primary studies 34
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Balakittnen 2024 A novel saliva-based miRNA profile to diagnose and predict oral cancer DOI:10.1038/s41368-023-00273-w | 2024 | 2 other reviews | not stated | not extracted yet |
| Balakittnen 2024 A novel saliva-based miRNA profile to diagnose and predict oral cancer. PMID:38368395 | 2024 | 2 other reviews | not stated | not extracted yet |
| Garg 2023 Evaluation of Diagnostic Significance of Salivary miRNA-184 and miRNA-21 in Oral Squamous Cell Carcinoma and Oral Potentially Malignant… PMID:38015343 | 2023 | 2 other reviews | not stated | not extracted yet |
| Ghallab 2016 Serum and salivary levels of chemerin and MMP-9 in oral squamous cell carcinoma and oral premalignant lesions. PMID:27161218 | 2017 | 2 other reviews | not stated | not extracted yet |
| Romani 2021 Genome-wide study of salivary miRNAs identifies miR-423-5p as promising diagnostic and prognostic biomarker in oral squamous cell carcinoma. PMID:33456584 | 2021 | 2 other reviews | not stated | not extracted yet |
| Tarrad 2023 "Salivary LINC00657 and miRNA-106a as diagnostic biomarkers for oral squamous cell carcinoma, an observational diagnostic study". PMID:38087258 | 2023 | 2 other reviews | not stated | not extracted yet |
| Duz 2016 Identification of miR-139-5p as a saliva biomarker for tongue squamous cell carcinoma: a pilot study. PMID:26650483 | 2016 | 1 other review | not stated | not extracted yet |
| Garg 2023 Evaluation of Diagnostic Significance of Salivary miRNA-184 and miRNA-21 in Oral Squamous Cell Carcinoma and Oral Potentially Malignant… DOI:10.1007/s12105-023-01600-7 | 2023 | 1 other review | not stated | not extracted yet |
| He 2020 Salivary exosomal miR-24-3p serves as a potential detective biomarker for oral squamous cell carcinoma screening. PMID:31704611 | 2020 | 1 other review | not stated | not extracted yet |
| Lee 2018 Evaluation of saliva and plasma cytokine biomarkers in patients with oral squamous cell carcinoma. PMID:29174861 | 2018 | 1 other review | not stated | not extracted yet |
| Mehterov 2022 A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosa. PMID:36531016 | 2022 | 1 other review | not stated | not extracted yet |
| Scholtz 2022 Salivary miR-31-5p, miR-345-3p, and miR-424-3p Are Reliable Biomarkers in Patients with Oral Squamous Cell Carcinoma. PMID:35215172 | 2022 | 1 other review | not stated | not extracted yet |
| Tarrad 2023 “Salivary LINC00657 and miRNA-106a as diagnostic biomarkers for oral squamous cell carcinoma, an observational diagnostic study” DOI:10.1186/s12903-023-03726-0 | 2023 | 1 other review | not stated | not extracted yet |
| Wan 2017 Salivary miRNA panel to detect HPV-positive and HPV-negative head and neck cancer patients. PMID:29245955 | 2017 | 1 other review | not stated | not extracted yet |
| Anu 2021 Identification of potential salivary biomarker panels for oral squamous cell carcinoma DOI:10.1038/s41598-021-82635-0 | 2021 | this review only | not stated | not extracted yet |
| Anu 2021 Identification of potential salivary biomarker panels for oral squamous cell carcinoma. PMID:33564003 | 2021 | this review only | not stated | not extracted yet |
| Awasthi 2017 Role of salivary biomarkers in early detection of oral squamous cell carcinoma DOI:10.4103/ijpm.ijpm_140_16 | 2017 | this review only | not stated | not extracted yet |
| Awasthi 2017 Role of salivary biomarkers in early detection of oral squamous cell carcinoma. PMID:29323056 | 2017 | this review only | not stated | not extracted yet |
| Chu 2024 Clinical validation of a saliva-based matrix metalloproteinase-1 rapid strip test for detection of oral cavity cancer DOI:10.1016/j.bj.2023.04.002 | 2024 | this review only | not stated | not extracted yet |
| Chu 2024 Clinical validation of a saliva-based matrix metalloproteinase-1 rapid strip test for detection of oral cavity cancer. PMID:37044249 | 2024 | this review only | not stated | not extracted yet |
| Duz 2016 Identification of miR-139-5p as a saliva biomarker for tongue squamous cell carcinoma: a pilot study DOI:10.1007/s13402-015-0259-z | 2015 | this review only | not stated | not extracted yet |
| Gai 2018 Salivary extracellular vesicle-associated miRNAs as potential biomarkers in oral squamous cell carcinoma DOI:10.1186/s12885-018-4364-z | 2018 | this review only | not stated | not extracted yet |
| Gai 2018 Salivary extracellular vesicle-associated miRNAs as potential biomarkers in oral squamous cell carcinoma. PMID:29669525 | 2018 | this review only | not stated | not extracted yet |
| Ghallab 2016 Serum and salivary levels of chemerin and MMP-9 in oral squamous cell carcinoma and oral premalignant lesions DOI:10.1007/s00784-016-1846-8 | 2016 | this review only | not stated | not extracted yet |
| He 2020 Salivary exosomal miR-24-3p serves as a potential detective biomarker for oral squamous cell carcinoma screening DOI:10.1016/j.biopha.2019.109553 | 2020 | this review only | not stated | not extracted yet |
| Kumar 2025 Evaluation of salivary and serum Exosomal mRNAs as biomarkers for the diagnosis and prognosis of oral squamous cell carcinoma DOI:10.1038/s41598-025-22246-1 | 2025 | this review only | not stated | not extracted yet |
| Kumar 2025 Evaluation of salivary and serum Exosomal mRNAs as biomarkers for the diagnosis and prognosis of oral squamous cell carcinoma. PMID:41184439 | 2025 | this review only | not stated | not extracted yet |
| Lee 2018 Evaluation of saliva and plasma cytokine biomarkers in patients with oral squamous cell carcinoma DOI:10.1016/j.ijom.2017.09.016 | 2018 | this review only | not stated | not extracted yet |
| Mehterov 2022 A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosa DOI:10.3389/fonc.2022.1072579 | 2022 | this review only | not stated | not extracted yet |
| Rapado-Gonzalez 2022 Integrity and quantity of salivary cell‐free <scp>DNA</scp> as a potential molecular biomarker in oral cancer: A preliminary study DOI:10.1111/jop.13299 | 2022 | this review only | not stated | not extracted yet |
| Rapado-Gonzalez 2022 Integrity and quantity of salivary cell-free DNA as a potential molecular biomarker in oral cancer: A preliminary study. PMID:35416334 | 2022 | this review only | not stated | not extracted yet |
| Wan 2017 Salivary miRNA panel to detect HPV-positive and HPV-negative head and neck cancer patients DOI:10.18632/oncotarget.21725 | 2017 | this review only | not stated | not extracted yet |
| Zhao 2018 Salivary Circular RNAs Hsa_Circ_0001874 and Hsa_Circ_0001971 as Novel Biomarkers for the Diagnosis of Oral Squamous Cell Carcinoma DOI:10.1159/000491624 | 2018 | this review only | not stated | not extracted yet |
| Zhao 2018 Salivary Circular RNAs Hsa_Circ_0001874 and Hsa_Circ_0001971 as Novel Biomarkers for the Diagnosis of Oral Squamous Cell Carcinoma. PMID:29991057 | 2018 | this review only | not stated | 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 OSCC and healthy control cohorts screened to exclude oral inflammatory pathologies | Patients with OSCC and healthy controls (1628 participants; 18 studies; 45 datasets) |
| Intervention | Salivary biomarkers (proteomic, genomic, transcriptomic) validated by standardized molecular or immunoassay techniques | Salivary proteins, cytokines, cfDNA, single and panel miRNAs, circRNAs, EV miRNAs (n=45 datasets) |
| Comparison | Histopathological confirmation as reference standard | Histopathology |
| Outcomes | Sensitivity, specificity, DOR, AUC, likelihood ratios (2x2 data required) | Pooled sensitivity 0.64, specificity 0.71, DOR 4.53, AUC 0.75, LR+ 2, LR- 0.47 |
| Study designs | Diagnostic accuracy studies: case-control, cross-sectional, cohort | Case-control (majority), cross-sectional, prospective cohort (n=18) |
| Timing | Not specified | Not specified |