Expression of CDKN2A Gene for Early Detection of Head and Neck Squamous Cell Carcinoma - An Evaluative Study

Oral squamous cell carcinoma (OSCC) is difficult to detect at an early stage using routine imaging or biopsy. Cyclin-dependent kinase inhibitor 2A ( CDKN2A ) is a major tumour-suppressor gene in OSCC, and alterations in its gene expression reflect early molecular changes during carcinogenesis. This study aims to evaluate CDKN2A gene expression in untreated early-stage OSCC patients and assess its potential relevance for early disease detection.

Sixty participants (30 early-stage OSCC patients and 30 matched healthy controls) were included. From OSCC patients, ribonucleic acid (RNA) was isolated from matched tumour and adjacent normal mucosal tissues. CDKN2A gene expression levels were quantified using quantitative reverse-transcription polymerase chain reaction with normalisation to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Human papillomavirus status and clinical features were assessed to interpret biomarker performance. Statistical analysis used the Wilcoxon signed-rank test for paired tissue data, with P < 0.05 considered significant.

CDKN2A mRNA expression was significantly lower in OSCC tumour tissue than in adjacent normal mucosa in the present cohort (median 0.65 vs 1.15, P < 0.05). The Cancer Genome Atlas head and neck squamous cell carcinoma (HNSCC) data ( n = 520) showed higher CDKN2A transcript levels in tumours compared with normal tissues. However, oral cavity-specific analysis showed no significant difference ( P = 0.693), which was similar to the findings observed in HPV-negative oral tumours in the present study.

CDKN2A mRNA is significantly downregulated in early-stage HPV-negative OSCC tissue and may serve as a tissue-based molecular marker. Biofluid CDKN2A mRNA shows low sensitivity for non-invasive screening. Larger cohorts and multi-marker panels may improve its diagnostic performance and clinical utility in early detection.