# MMP-9 as a diagnostic salivary biomarker for early detection of oral cancers: systematic review and meta-analysis

**Authors:** Aqsa Shaukat, Saleha Nisar, Mehmood Asghar, Muhammad Kaleem, Muhammad Sohail Zafar

PMC · DOI: 10.1186/s12903-025-07513-x · BMC Oral Health · 2026-01-03

## TL;DR

This study reviews and analyzes the effectiveness of using salivary MMP-9 as a diagnostic biomarker for early-stage oral cancer.

## Contribution

The study provides a systematic review and meta-analysis of salivary MMP-9's diagnostic accuracy for early-stage oral cancer.

## Key findings

- Salivary MMP-9 showed high pooled sensitivity and specificity for detecting early-stage oral cancer.
- The study found a high area under the curve (0.97) for salivary MMP-9 as a diagnostic biomarker.
- The study highlights the need for further research due to high heterogeneity and risk of bias.

## Abstract

The intention of this investigation was to evaluate the diagnostic performance of salivary MMP-9 enzyme for rapid point of care testing of early stage (I, II) oral cancer. Diagnosis at early pre-malignant stages will help in making clinical decisions for timely intervention.

Original diagnostic test accuracy (DTA) studies of any design, on patients with lip and oral cavity cancers investigating salivary MMP-9 levels as an index test and histopathological confirmation via biopsy as a reference test were eligible for inclusion. Similar studies on serum or blood were excluded. Besides, the case reports/case series, reviews, letters, book chapters, conference abstracts, in vitro, and animal studies were all excluded. Non-English papers were not excluded. The databases searched from Jan 2014 to Aug 2024 were PubMed, SCOPUS, Cochrane Library, Science Direct, and Google Scholar, without language restrictions. QUADAS-2 was used to assess the risk of bias and concerns regarding applicability. Meta-analyses were performed using a bivariate random-effects model.

Out of 18 articles identified, 7 studies with 795 patients were included. The pooled sensitivity, specificity, mean salivary MMP-9 levels, and the Summary Receivers Operating Curve were done using REVMAN 5.4 and a web application (Meta-DiSc 2.0). Overall, the pooled sensitivity, specificity, and Area under the curve were 0.98, 0.96, and 0.97, respectively with 95% confidence interval between 0.85 and 1. However, with high heterogeneity and risk of bias together with low applicability concern we need additional pragmatic designed research to back up its use in screening and diagnostic applications.

Within the limitations of the study, salivary MMP-9 has merit as a biomarker for identification of early-stage (I, II) oral cancer.

The online version contains supplementary material available at 10.1186/s12903-025-07513-x.

## Linked entities

- **Proteins:** MMP9 (matrix metallopeptidase 9)
- **Diseases:** oral cancer (MONDO:0023644)

## Full-text entities

- **Genes:** MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}
- **Diseases:** (I, II) (MESH:D056829), oral cancer (MESH:D009062), lip and oral cavity cancers (MESH:D008048)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12866002/full.md

## References

8 references — full list in the complete paper: https://tomesphere.com/paper/PMC12866002/full.md

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Source: https://tomesphere.com/paper/PMC12866002