The Use of Salivary Levels of Matrix Metalloproteinases as an Adjuvant Method in the Early Diagnosis of Oral Squamous Cell Carcinoma: A Narrative Literature Review

Abstract

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with increased mortality, in which the early diagnosis is the most important step in increasing patients’ survival rate. Extensive research has evaluated the role of saliva as a source of diagnostic biomarkers, among which matrix metalloproteinases (MMPs) have shown a valuable potential for detecting even early stages of OSCC. The aim of this review was to present recent clinical data regarding the significance of salivary MMPs in the detection of early malignant transformation of the oral mucosa. A narrative review was conducted on articles published in PubMed, Cochrane Library, Web of Science, EBSCO and SciELO databases, using specific terms. Our search revealed that MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-12 and MMP-13 had significantly higher levels in saliva from patients with OSCC compared to controls. However, the strength of evidence is limited, as most information regarding their use as adjuvant diagnostic tools for OSCC comes from studies with a low number of participants, variable methodologies for saliva sampling and diagnostic assays, and insufficient adjustment for all covariates. MMP-1, MMP-3 and MMP-9 were considered the most promising candidates for salivary diagnosis of OSCC, but larger studies are needed in order to validate their clinical application.

High-Multiplex Aptamer-Based Serum Proteomics to Identify Candidate Serum Biomarkers of Oral Squamous Cell Carcinoma

“…As important representatives, tissue inhibitor of matrix metalloproteinases-2 (TIMP2), interstitial collagenase MMP-1, gelsolin, peroxiredoxin 1 and glia-derived nexin were significantly up-regulated, and various components of the complement cascade, cathepsin A and angiostatin were down-regulated in the tumor vs. healthy control group. Notably, several of these proteins were previously found to be up- or down-regulated in tissue specimens or cell cultures of OSCC vs. controls [ 48 , 49 , 50 , 51 , 52 , 53 , 54 ].…”

Matrix Metalloproteinases in the Periodontium—Vital in Tissue Turnover and Unfortunate in Periodontitis

“…Capable of degrading all proteinaceous ECM components, MMPs are involved in multiple processes in the body, playing a role not only in pathological but also in physiological processes [ 5 ]. MMP activity is implicated in various pathologies of the oral cavity, for example, dental erosion, dental caries, pulpitis, periapical periodontitis, and oral cancer invasion and metastasis [ 6 , 7 ]. Moreover, being implicated in odontogenesis and tissue turnover, impaired MMP activity may result in deficient enamel mineralization or in gingival overgrowth [ 8 , 9 ].…”

Analyzing the Salivary Levels of Cathepsin B in Oral Submucous Fibosis and Oral Squamous Cell Carcinoma for Early Detection

“…Histopathological examination of biopsy samples is still required for further con rmation and is considered as the gold standard method for diagnosis of OSCC (20). Biopsy has several disadvantages as it is a very invasive, painful, lengthy and expensive procedure with fear of spread of cancer and also requires expert pathologist (21,22). This results in delayed diagnosis and as a consequence one third of OSF patients develop OSCC (23).…”

“…OSCC diagnosis by using salivary biomarkers is considered as the most optimistic and promising approach because of direct contact between oral cancer and saliva (25). The saliva can be considered a very good and reliable biological sample for diagnosis of oral cancer owing to its simple, safe, noninvasive and cost-effective nature (22). Furthermore, its ease in availability and processing makes saliva a perfect tool for oral cancer detection.…”