Neoangiogenesis in oral submucous fibrosis in the Indian population: a systematic review and meta-analysis of CD105 (Endoglin) expression

Oral submucous fibrosis (OSMF) is a chronic, progressive, potentially malignant oral disorder characterized by progressive mucosal fibrosis and restricted mouth opening, predominantly affecting populations in the Indian subcontinent. Persistent fibrosis and tissue remodeling may create a hypoxic microenvironment that promotes neoangiogenesis during disease progression. CD105 (Endoglin), a marker preferentially expressed by activated and proliferating endothelial cells, may therefore indicate active neoangiogenesis in OSMF. This systematic review and meta-analysis evaluated CD105-assessed microvessel density (CD105-MVD) in OSMF compared with normal oral mucosa and examined its association with disease severity, including differences between early and advanced OSMF. Systematic literature search was performed in electronic databases like PubMed, Scopus, and Web of Science from inception to April 2026, following the PRISMA 2020 protocol. The review protocol was prospectively registered with PROSPERO (CRD420261284900). Studies evaluating CD105-MVD in tissue samples of histopathologically and clinically diagnosed OSMF cases were included. Risk of bias in the studies was evaluated using the Newcastle-Ottawa Scale. Random effects meta-analysis was performed using standardized mean difference (SMD) to compare OSMF with normal oral mucosa (NOM) and advanced with early OSMF stages. Seven cross-sectional studies from India were included in this review. The meta-analysis of three studies showed that CD105-MVD was significantly higher in OSMF than in NOM (SMD = 1.81; 95% CI: 0.65–2.96; p = 0.002), with substantial heterogeneity (I² = 87.6%). Although CD105-MVD was found to be higher in advanced OSMF than in early OSMF, this difference was not statistically significant (SMD = 1.08, 95% CI: −0.36–2.51; p = 0.143), with substantial heterogeneity (I² = 91.0%). Given the small number of studies contributing to each comparison, these pooled estimates were considered exploratory. The results of the narrative synthesis revealed progressive increases in CD105-MVD from NOM to Dysplastic OSMF and OSCC. The majority of the studies had moderate methodological quality. CD105-MVD is associated with hypoxia-related neoangiogenic alterations in OSMF and may have potential as an auxiliary biomarker for risk assessment of malignant transformation. However, the present findings are based on cross-sectional studies only, and longitudinal studies are needed for the predictive role of CD105-MVD.