An enigmatic pathogenetic mechanism of hypoxia inducible factor - 1/2 alpha in the progression of fibrosis of oral submucous fibrosis and its malignant transformation: A systematic review and meta-analysis

Abstract

Objective: Oral submucous fibrosis is a frequently reported potentially malignant disorder characterized by fibrosis and a malignant transformation rate of 7-30%. The role of hypoxia-inducible factor-1/2α in malignant transformation mechanisms of oral submucous fibrosis remains uncharted territory owing to a scarcity of studies. Thus the present systematic review and meta-analysis aimed to determine the role of hypoxia-inducible factor-1/2α in the progression of fibrosis of oral submucous fibrosis and its malignant transformation.

Material and methods: Using PubMed, Google Scholar, and Cochrane Library databases, full-text articles that investigated hypoxia-inducible factor-1/2α in oral submucous fibrosis were entailed for review. A modified Newcastle-Ottawa scale was employed to evaluate risk of bias in all articles and Review Manager was utilized for meta-analysis.

Results: Eighteen and eight qualified articles respectively were included for qualitative and quantitative data synthesis. Progressive upregulation of hypoxia-inducible factor-1/2α in oral submucous fibrosis is associated with fibrosis-induced carcinogenesis. A Random-effects model uncloaked that oral submucous fibrosis cases with significantly increased expression of hypoxia-inducible factor-1α had an increased associated risk of malignant transformation compared with controls (combined odds ratio 523.83, 95% confidence interval 125.74- 2182.28, p < 0.00001).

Conclusion: The existing evidence substantiates the notion that hypoxia-inducible factor-1/2α, a fundamental pathogenetic mechanism of progression and malignant transformation of oral submucous fibrosis in the background of fibrosis.

Keywords: HIF-1/2α, Hypoxia-inducible factor; Malignant transformation; OSMF; Oral submucous fibrosis.