Role of inflammatory markers in oral squamous cell carcinoma - A prognostic systematic literature review with emphasis on gingival squamous cell carcinoma.

Gingival squamous cell carcinoma (GSCC) is a rare subset of oral squamous cell carcinoma (OSCC), often mimicking benign or inflammatory lesions, which complicates early diagnosis. Chronic inflammation plays a pivotal role in oral carcinogenesis, yet its molecular implications in GSCC remain underexplored. This Prognostic Systematic Literature Review (SLR) presents a case-based review of GSCC and evaluates the immunohistochemical expression of key inflammatory markers - COX-2, TNF-α, IL-6, NF-κB, VEGF, iNOS, Bcl-2/Bax ratio, and HDAC6 - in OSCC to assess their diagnostic, prognostic, and therapeutic relevance. Literature search was done (1999-2025) across PubMed, Scopus, Web of Science, Cochrane, and Google Scholar to identify studies on biomarker analysis in histopathologically confirmed cases of OSCC. Data extraction focused on clinical presentation, tumour grade, invasion, metastasis, and survival. Study quality was assessed using NOS and JBI tools. From 1055 screened records,18 studies met inclusion criteria. GSCC is often masqueraded as desquamative gingivitis or periodontal abscess, causing diagnostic delays. Immunohistochemistry revealed frequent overexpression of COX-2, TNF-α, VEGF, and Bcl-2, correlating with tumour aggressiveness, angiogenesis, higher histological grade, and poor prognosis. Temporal trends indicate a shift from apoptotic dysregulation to cytokine-driven inflammatory phenotypes as key drivers of OSCC progression. To Conclude, GSCC requires high clinical vigilance due to its deceptive presentation. Biomarkers such as COX-2, TNF-α, IL-6, NF-κB, and VEGF provide critical prognostic and therapeutic insights, emphasising the role of inflammation in tumour progression and supporting biomarker-guided early detection strategies.