The Putative Role of Mast Cells in Oral Leukoplakia-A Systematic Review and Meta-Analysis

Mast cells are believed to contribute to inflammation-associated carcinogenesis, but their specific role in the development of oral leukoplakia (OLK) and its progression to oral squamous cell carcinoma (OSCC) remains uncertain. This systematic review and meta-analysis aimed to determine whether mast cell density differs among normal oral mucosa (NOM), OLK, and OSCC.

A comprehensive literature search was conducted in PubMed, Scopus, Web of Science and Embase along with Google Scholar for studies that reported mast cell counts in OLK, OSCC, and NOM published up to September 30, 2025. Data were extracted, and the mean difference was calculated. Risk of bias was assessed using the JBI critical appraisal tool, and meta-analysis was performed using MetaAnalysisOnline.com.

Thirty-four studies were included for qualitative and 26 contributed to quantitative data synthesis. The studies opined that mast cells were highest in OSCC, followed by OLK and NOM. Mast cell density was higher in OSCC than in OLK; however, the difference was not significant. A random-effects model revealed a significant increase in mast cell density in OLK than NOM (p < 0.0001) and OSCC than NOM (p = 0.0055); however, when OLK was compared with OSCC, the difference was not significant (p = 0.2865).

The existing data validate that mast cells were increased in oral leukoplakia, indicating their potential involvement in early oral carcinogenesis; however, future studies focusing on the prognostic value of mast cells in oral leukoplakia are warranted.

PROSPERO number: CRD42024533723.