The Evolutionary Landscape of Inflammatory and Nutritional Biomarkers in Oral Squamous Cell Carcinoma: A Comprehensive Review of Pathogenesis and Prognosis

Abstract

Oral squamous cell carcinoma (OSCC) is a major health burden with a disproportionately high incidence in regions such as India due to cultural habits like tobacco and betel nut chewing. Despite significant therapeutic advancements, low overall survival rates are encountered in advanced cases. Tobacco, alcohol, and the human papillomavirus (HPV) are the traditional risk factors. Chronic inflammation has emerged as a pivotal driver in the transition from normal epithelium to malignancy. This process is largely governed by the transcription factor nuclear factor kappa B (NF-κB), which initiates pro-inflammatory signalling cascades that promote cell proliferation, inhibit apoptosis, and facilitate angiogenesis. Key cytokines such as TNF-α and IL-6 serve as critical indicators of poor prognosis. The host’s systemic inflammatory response (SIS) can offer cost-effective prognostic insights through peripheral blood markers. Specifically, a high pre-operative Neutrophil-to-Lymphocyte Ratio (NLR) is a robust independent predictor of poor survival, while elevated C-reactive protein (CRP) levels (>15 mg/L) significantly increase the hazard of head and neck cancer. Within the local tumour microenvironment, the presence of CD68+ tumour-associated macrophages correlate with metastasis, whereas a dense lymphocytic host response (LHR) indicates superior cytotoxic T-cell activity and improved clinical outcomes. Furthermore, nutritional status is vital, particularly in aged populations. The Prognostic Nutritional Index (PNI) is a robust predictor of 5-year survival. Local oral health disorders also act as precursors of invasive malignancy, with periodontitis and impacted teeth associated with sixfold and twelvefold increases in cancer hazard, respectively. Beyond biological markers, sociodemographic factors also impact the oncological outcomes of oral cancer. Integrating these systemic markers, nutritional indices, and oral health screenings into clinical practice, alongside the updated AJCC 8th edition staging system, is essential for improving early detection and developing personalised treatment strategies for OSCC.