Stott-Miller et al., 2011 [26]MMP-1, MMP-360 primary OSCC cases, 15 cases of oral dysplastic lesions and 25 controlsELISAHigher salivary concentration of MMPs in OSCC cases compared to controls (6.2 times higher for MMP-1 and 14.8 times higher for MMP-3);
Stronger results for both MMP-1 and MMP-3 in oral cavity cancer versus controls, rather than in oropharyngeal cancer versus controls;
Salivary concentrations of MMP-1 and MMP-3 correlated with tumor stage.MMPs may be very useful in monitoring dysplasia progression to OSCC;
Salivary MMP-1 can be an important biomarker of OSCC development. Chang et al., 2020 [27]MMP-1269 primary OSCC cases, 578 PMOLs and 313 healthy controlsELISAHigher salivary concentration of MMP-1 in OSCC cases than in non-cancerous patients (PMOLs and healthy controls);
Satisfactory reliability of MMP-1 in distinguishing OSCC from non-tumor lesions;
Good power of discrimination between OSCC located on the tongue, cheek mucosa, gum and multiple sites of the oral cavity from non-tumor lesions;
Higher salivary concentrations of MMP-1 in high-risk PMOLs compared to low-risk PMOLs and healthy controls;
Correlation of the salivary levels of MMP-1 with tumor size and lymph node metastasis.Useful salivary biomarker in evaluating malignant transformation;
Promising potential in early-stage screening of patients with increased risk for OSCC development;
Important biomarker of poor prognosis.Yu et al., 2016 [28]MMP-1, MMP-3, MMP-9, annexin-2 (ANXA2), Heat Shock Protein Family A (Hsp70) Member 5 (HSPA5) and other salivary proteins131 OSCC cases, 233 PMOLs and 96 healthy controlsLiquid chromatography–multiple reaction monitoring-mass spectrometryMMP-1 and kininogen 1 (KNG 1) had the highest salivary concentrations in OSCC patients among the analyzed salivary proteins;
The sensitivity and specificity of the analyzed MMPs in differentiating OSCC from healthy controls and low-risk PMOLs were: 69.5% and 95% for MMP-1, 62.6% and 76.9% for MMP-3 and 75.6% and 60.3% for MMP-9;An identified panel of 4 salivary biomarkers (MMP-1, KNG 1, ANXA2 and HSPA5) may represent a promising tool in the diagnosis of OSCC and in the monitoring of malignant transformation occurring in high-risk PMOLs.Feng et al., 2019 [29]MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, MMP-13 and other salivary proteins20 OSCC cases, 20 oral benign masses (OBM), 20 mild chronic periodontal disease (CPD) and 20 healthy controlsELISAMMP-1, MMP-2, MMP-3, MMP-10, MMP-12, MMP-13 were detected only in the saliva of patients with OSCC;
MMP-1, MMP-2, MMP-10, MMP-12 along with cathepsin V, A disintegrin and a metalloprotease 9 (ADAM9) and kallikrein 5 has higher salivary concentration in OSCC patients compared to OBM, CPD and healthy controls.By evaluating the combined sensitivity and specificity, the concomitant use of ADAM9, cathepsin V and kallikrein 5 was the most promising candidate for diagnosing OSCC.Cai et al., 2022 [30] MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, Hepatocyte growth factor (HGF) and other salivary proteins8 OSCC cases and 8 healthy controlsProtein chip
arrayHigher salivary concentrations of MMP-1, MMP-3, MMP-8, MMP-9, MMP-10 and MMP-13 in OSCC patients compared to controls, the most significant increases being observed for MMP-1, MMP-3 and MMP-13;
No difference between salivary concentration of MMP-2 in OSCC compared to controls; MMP-1, MMP-3 and MMP-13 were not detected in the saliva of healthy controls.
The salivary levels of HGF and MMP-9 significantly differed between OSCC patients and healthy subjects.Both HGF and MMP-9 can be useful biomarkers for the diagnosis and prognosis of OSCC.Agha-Hosseini et al., 2015 [31]MMP-1320 OSCC cases and 30 oral lichen planus (OLP)ELISANo differences between salivary concentrations of MMP-13 in OSCC patients compared to OLP.Salivary MMP-13 may not be a valuable adjuvant in the diagnosis and screening of OSCC.Ghallab and Shaker, 2017 [32]MMP-9 and chemerin15 early-stage OSCC cases, 15 PMOLs and 15 healthy controlsELISAHigher salivary levels of MMP-9 and chemerin in patients with OSCC compared to those with PMOLs and healthy subjects;
Higher salivary levels of MMP-9 and chemerin in PMOLs compared to healthy subjects;
Salivary MMP-9 had the greatest accuracy in distinguishing PMOLs from OSCC (sensitivity 100% and specificity 93%). Salivary MMP-9 and chemerin can be used as adjuvant tools in the early diagnosis of OSCC and PMOLs.Peisker et al., 2017 [33]MMP-930 OSCC cases and 30 healthy controlsELISAHigher salivary levels of MMP-9 in OSCC patients compared to healthy controls.
Salivary MMP-9 had 100% sensitivity and 26.7% specificity in diagnosing OSCC.Salivary MMP-9 may be a complementary tool for the early diagnosis of OSCC.Shin et al., 2021 [34]MMP-9 and 8-hydroxydeoxy-
guanosine (8-OHdG)106 OSCC cases and 212 healthy controlsELISAThe salivary levels of MMP-9 in OSCC patients were 17 times higher than those of healthy controls;
After surgical excision of the tumor, salivary MMP-9 decreased by 80% in the first nine months but was still higher in comparison with the value in healthy controls;
The diagnostic ability of salivary MMP-9 after adjusting covariates showed 97.2% sensitivity and 94.2% specificity;Salivary MMP-9 may be used in the early diagnosis and screening of OSCC.Smriti et al., 2020 [35]MMP-924 OSCC cases, 20 PMOLs, 22 subjects consuming tobacco and 22 healthy controlsELISAHigher levels of MMP-9 in the saliva of patients with OSCC and PMOLs compared to tobacco users and healthy controls;
Salivary levels of MMP-9 increased according to tumor stage and were higher in poorly differentiated tumors;Salivary MMP-9 can aid in the diagnosis of OSCC and PMOLs. Saleem et al., 2021 [36]MMP-1230 OSCC cases, 30 patients with oral submucous fibrosis (OSF) and 30 healthy controlsELISAHigher levels of MMP-12 in the saliva of patients with OSCC and OSF compared to healthy controls and also in OSCC group compared to OSF group;
Salivary MMP-12 had 100% sensitivity and 100% specificity in detecting OSF and OSCC.Salivary MMP-12 can be an adjuvant method in the early diagnosis of OSF and OSCC.