Abstract
BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent malignancy of the head and neck, often only diagnosed at advanced stages due to the limitations of conventional diagnostic tools. Early detection is crucial for improving survival rates, minimising treatment-related morbidity, and enhancing patient outcomes. Immunohistochemical (IHC) markers have emerged as potential tools for identifying early molecular changes associated with malignant transformation in oral epithelial cells. OBJECTIVE: This systematic review aims to evaluate the diagnostic performance of IHC markers in the early detection of OSCC, focusing on their sensitivity, specificity and clinical applicability. METHODS: A systematic literature search was conducted for relevant studies published between 2015 and 2025. After removing duplicates using Mendeley Software, 412 studies were identified. A total of 168 studies were excluded following title screening, and 181 were excluded based on abstract screening. Sixty-three full-text articles were reviewed for eligibility. An additional 20 studies were identified through reference list screening. After applying the inclusion and exclusion criteria, 6 studies were included in the final analysis. RESULTS: The review identified several IHC markers, including p53, Ki-67, EGFR, and p16, as frequently associated with early dysplastic changes and malignant transformation in the oral mucosa. While many markers showed high sensitivity and specificity, variability in study design, antibody clones, interpretation criteria, and staining protocols limited the generalisability of the findings. CONCLUSION: IHC markers demonstrate considerable potential for the early identification of OSCC. However, standardised protocols, large-scale multicentre validation studies, and integration with molecular diagnostics are needed to establish their clinical utility. The findings of this review support the incorporation of IHC markers into evidence-based diagnostic approaches to improve early detection and patient prognosis in OSCC.