Molecular and Cellular Basis of Oral Lichen Planus: Bridging Pathogenesis and Modern Clinical Paradigms

Oral lichen planus (OLP) is a chronic, T cell-mediated inflammatory disorder classified by the World Health Organization as an oral potentially malignant disorder (OPMD). Despite decades of research, its precise etiology remains incompletely understood and involves a complex interplay between genetic predisposition, environmental triggers, and autoimmune-like responses. This review provides a comprehensive update on OLP pathogenesis, emphasizing the role of CD8 positive cytotoxic T lymphocyte-driven basal keratinocyte apoptosis and the skewing of the T-cell receptor (TCR) repertoire. We highlight the significance of the epidermal growth factor receptor (EGFR) signaling pathway as a molecular bridge between chronic inflammation and epithelial proliferation. Furthermore, we discuss a stepwise therapeutic approach that prioritizes the management of the oral microenvironment—specifically Candida colonization and periodontal health—before escalating to immunosuppressive agents. Finally, we explore emerging precision medicine frontiers, including IL-17/IL-23 inhibitors and JAK inhibitors, alongside traditional Japanese Kampo medicine (Hange-shashin-to) and systemic adjuncts like Cepharanthine, offering a contemporary perspective on modern OLP management. This integrative framework redefines OLP not merely as a chronic inflammatory disorder, but as an immunologically sustained, microenvironment-driven, potentially malignant condition.