Human leukocyte antigen and its association with oral potentially malignant disorders - a Systematic review and Meta-analysis

Background: The Human Leukocyte Antigen (HLA) genes, located within the Major Histocompatibility Complex on chromosome 6p21, are highly polymorphic and play a vital role in immunity and has strong associations with autoimmune disorders. However, its role in cancers including oral cancers and oral potentially malignant disorders (OPMD) is still being explored and there is no strong evidence available for this association. Hence the present systematic review was performed to synthesize the current available evidence of genetic propensity of HLA alleles in protective or susceptibility role in occurrence of OPMD. Methods: A thorough search was conducted in Medline, PubMed, Cochrane, Scopus, Web of Science, EMBASE databases for relevant articles until June 2024. PRISMA guidelines were followed for conducting the systematic review. Of the nine studies selected for review, five evaluated the association of HLA with Lichen Planus, three studies were conducted in oral submucous fibrosis (OSF) patients and remaining one study dealt with all oral lesions including OPMDs. A total of 6493 participants from 9 studies were eligible for the systematic review, HLA association was compared between 757 diagnosed patients of OPMD and 5736 control group. The risk of bias was assessed using the Newcastle-Ottawa tool, with most of the studies indicating fair to good quality. Results: Studies across varied ethnic groups showed that HLA-DR2 and HLA-DR6 antigen group which includes DRB1*14 alleles were observed more frequently in oral lichen planus while HLA-B7, HLA-A10 and HLA-DR3 were reported to be associated with oral submucous fibrosis. Conclusion: Certain HLA alleles have more predilection towards occurrence of oral premalignant disorders. Hence, future multiethnic large scale population studies are recommended to understand the molecular mechanism behind the occurrence OPMD, so that HLA can be developed as potential biomarker in diagnosis and/or treatment of OPMD.