Abstract
Introduction: Oral leukoplakia (OLK) and oral lichen planus (OLP) are recognized as potentially malignant disorders with varying risks of progression to oral squamous cell carcinoma (OSCC). Immunohistochemical (IHC) biomarkers have been extensively studied to identify predictive markers for malignant transformation in these lesions.
Objectives: This systematic review synthesizes current evidence on IHC biomarkers associated with malignant progression in OLK and OLP. Materials and
Methods: In this systematic review study, a systematic literature search was conducted across databases, including PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar search engine up to April 2025. Studies included were those investigating IHC biomarkers in OLK and OLP with reported malignant transformation outcomes.
Results: This systematic review included 10 studies with a total of 549 participants. The most frequently assessed IHC markers were B-cell lymphoma 2 (Bcl-2), p53, Ki-67, Bcl-2-associated X protein (Bax), survivin, mouse double minute 2 homolog (MDM2), and proliferating cell nuclear antigen (PCNA). Bcl-2 was the predominant marker, evaluated in 9 studies, followed by p53 was examined in 7, Ki-67 in 4, and Bax in 3 studies. Less commonly studied markers included survivin, MDM2, PCNA, and p21, each reported in a single study.
Conclusion: Although Bcl-2 and p53 emerge as the most significant IHC markers for predicting malignant transformation in oral premalignant lesions due to their roles in apoptosis and tumor suppression, the Ki-67 and Bax biomarkers contribute important information on cell proliferation and apoptotic balance, while markers like survivin, MDM2, PCNA, and p21 are less commonly studied but may have specialized roles. Overall, a panel of these biomarkers, especially Bcl-2 and p53, shows strong potential for improving risk assessment and guiding clinical management of OLK and OLP.
Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD420251063588) and Research Registry (UIN: reviewregistry2021) websites.