Aberrant PAX6 Expression in Cervical Cancer: Integrated Molecular Profiling and Clinical Cohort Evaluation

Abstract Background: Paired box 6 (PAX6) is a developmental transcription factor implicated in multiple malignancies, but its molecular and clinical associations in cervical cancer remain incompletely characterized. This study investigated PAX6 expression, HPV16-associated alterations, developmental gene networks, and clinical outcomes in cervical cancer. Materials & Methods: Integrated analyses of TCGA-CESC and public molecular databases evaluated PAX6 transcript expression, HPV16 status, genomic alterations, protein-expression patterns, survival outcomes, and developmental gene associations. Peripheral-blood PAX6 expression was independently assessed using quantitative real-time PCR in 103 cervical cancer patients receiving cisplatin-based chemoradiotherapy and 108 healthy controls. Results: PAX6 expression was elevated in cervical cancer tissues (GEPIA3, p = 0.000542) and HPV16-positive tumours (n = 175) compared with HPV16-negative tumours (n = 14; p = 2.2 × 10⁻⁷). Exploratory survival analyses showed divergent associations with overall survival (HR = 0.62, 95% CI 0.39–0.99) and relapse-free survival (HR = 2.32, 95% CI 1.06–5.06). In 304 primary tumours, PAX6 correlated weakly with SOX2 (ρ = 0.296) and SIX3 (ρ = 0.274), both significant after false-discovery-rate correction. Peripheral-blood PAX6 was elevated in 84/103 patients (81.6%; p = 0.001), without significant associations with chemoradiotherapy response (p = 0.804) or overall survival. Conclusions: PAX6 exhibits altered expression in cervical cancer, with associations involving HPV16 status, developmental transcriptional networks, and selected survival outcomes. Peripheral-blood findings provide complementary clinical evidence, but independent validation is required to establish prognostic utility.