Epigenetic mechanisms of oral leukoplakia: a systematic review / Noor Azliza Wani Abd. Aziz ... [et al.]

Objectives: Oral leukoplakia (OL) is the most common type of oral potentially malignant disorder and has a malignancy transformation rate ranging from 0.1% to 17.5%. The rates of malignant transformation of OL to oral carcinoma can reach as high as 70%. Epithelial dysplasia in OL is linked to progression toward malignant transformation. We performed a systematic review (SR) to identify the epigenetic alterations associated with OL and their role in its progression.
Methods: The study protocol was registered in PROSPERO, ID: CRD42024497161. We searched PubMed, MEDLINE, Scopus, ScienceDirect, Web of Science, ClinicalKey and Wiley databases from 2018 to 2023. This SR was conducted following PRISMA guidelines, and articles were selected based on predefined inclusion and exclusion criteria.
Results: Seven studies met the inclusion criteria. Results documented that epigenetic mechanisms underlying malignant transformation of OL involved hyper and hypo methylation of CpG promoter in tumor suppressor gene, enhancer of zeste homolog 2 (EZH2) expressing cells in both the epithelium and connective tissues, methylation in retinoic acid receptor-beta (RARβ) promoter, involvement of non-coding miRNA which correlated positively with the degree of dysplasia, while salivary miRNA demonstrated potential as biomarker for the diagnosis and follow-up of OL patients.
Conclusion: Epigenetic non-coding miRNA biomarkers have potential mechanistic role in the early diagnosis of OL and serve as prognostic markers for its malignant transformation.