Purohit Bharathi M, Kanga Uma, Singh Abhinav, Priya Harsh
Asssociate Professor, Division of Public Health Dentistry, Centre for Dental Education and Research, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
Asssociate Professor, Division of Public Health Dentistry, Centre for Dental Education and Research, All India Institute of Medical Sciences (AIIMS), New Delhi, India; Additional Professor, Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
Hum Immunol. 2025 Jun 18;86(4):111335. doi: 10.1016/j.humimm.2025.111335.
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.
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.
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.
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.
人类白细胞抗原（HLA）基因位于6号染色体p21的主要组织相容性复合体中，具有高度多态性，在免疫中起关键作用，且与自身免疫性疾病密切相关。然而，其在包括口腔癌和口腔潜在恶性疾病（OPMD）在内的癌症中的作用仍在探索中，目前尚无有力证据支持这种关联。因此，本系统综述旨在综合目前关于HLA等位基因在OPMD发生中起保护或易感性作用的遗传倾向的现有证据。
截至2024年6月，在Medline、PubMed、Cochrane、Scopus、Web of Science、EMBASE数据库中对相关文章进行了全面检索。遵循PRISMA指南进行系统综述。在选定进行综述的9项研究中，5项评估了HLA与扁平苔藓的关联，3项研究针对口腔黏膜下纤维化（OSF）患者开展，其余1项研究涉及包括OPMD在内的所有口腔病变。9项研究中的6493名参与者符合系统综述条件，比较了757名经诊断的OPMD患者与5736名对照组之间的HLA关联。使用纽卡斯尔-渥太华工具评估偏倚风险，大多数研究表明质量为中等至良好。
不同种族群体的研究表明，在口腔扁平苔藓中更频繁观察到HLA-DR2和包括DRB1*14等位基因的HLA-DR6抗原组，而据报道HLA-B7、HLA-A10和HLA-DR3与口腔黏膜下纤维化有关。
某些HLA等位基因对口腔癌前病变的发生更具偏好性。因此，建议未来开展多民族大规模人群研究，以了解OPMD发生背后的分子机制，从而将HLA开发为OPMD诊断和/或治疗中的潜在生物标志物。
