Assessment of Programmed Cell Death Ligand-1 Expression in Oral Potentially Malignant Disorders and Tumor-Free Surgical Margins of Oral Squamous Cell Carcinoma: Protocol for a Retrospective Cross-Sectional Study

Background: Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy of the oral cavity, frequently preceded by oral potentially malignant disorder (OPMD). Despite therapeutic advances, survival rates remain unsatisfactory, primarily due to late diagnosis, recurrence, and molecular alterations in histologically tumor-free surgical margins. Programmed cell death ligand-1 (PD-L1), an immune checkpoint molecule, contributes to tumor immune evasion and has been implicated in cancer progression. Its expression in OPMDs and OSCC surgical margins may serve as an early indicator of malignant transformation and recurrence risk. Objective: This study aims to assess PD-L1 expression in OPMDs and histologically negative surgical margins of OSCC and evaluate their association with 3-year survival outcomes. Methods: This retrospective cross-sectional study will be conducted over 12 months at a tertiary care hospital in Sawangi Meghe, Wardha, India. Archived formalin-fixed, paraffin-embedded samples of OPMDs and tumor-free surgical margins from OSCC cases (2018-2020) will be retrieved. Immunohistochemistry for PD-L1 will be performed using the SP263 clone, and expression will be evaluated using the combined positive score. Demographic, clinical, and survival data will be collected from patient records. Statistical analysis will determine correlations among PD-L1 expression, clinicopathological variables, and 3-year survival. Results: The study is expected to provide insights into the role of PD-L1 as a biomarker for early detection, prognostication, and risk stratification in patients with OPMDs and OSCC. Data collection and immunohistochemical analysis have not yet commenced at the time of submission. Conclusions: By evaluating PD-L1 expression in premalignant lesions and histologically negative margins, this study aims to identify molecular predictors of OSCC progression and survival. The findings may help establish PD-L1 as a prognostic biomarker and support its integration into precision oncology and immunotherapy strategies.