HIGH-RISK HUMAN PAPILLOMAVIRUS ENHANCES THE EXPRESSION OF COX-2 VEGF, EGFR, PROEX-C, AND TERT PROTEINS IN HUMAN PAPILLOMAVIRUS-RELATED MULTIPHENOTYPIC SINONASAL CARCINOMA THROUGH ACTIVATION OF PI3K/AKT, PRB, AND TERT SIGNALLING PATHWAYS

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a new type of sinonasal tumour that frequently drops out of accurate di-agnosis. Human papillomavirus related multiphenotypic sinonasal carcinoma was previously known as HPV-related sinonasal carcinoma with adenoid cystic charac-teristics, and it is connected to high-risk HPV (HR-HPV) strains whose prognosis is unknown. We aim to evaluate PI3K/Akt, pRb, and h telomerase reverse tran-scriptase (TERT) signalling pathway activation through the expression of proteins cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), ProEx-C, and TERT and their prognostic and clinicopathological value in HMSC patients. Sections of the 40 paraffin blocks of HMSC were recovered, and all samples were evaluated for the presence of a cocktail of HR-HPV, and the absence of MYB, NFIB, and MYBL1 fusions using fluorescence in situ hybridization; the presence of myoepithelial markers; S100, actin; the presence of squamous differentiation markers; calponin, p40, and p63 using PCR-based assays; and COX-2,VEGF, ProEx-C, and TERT using immunohistochemical staining. All patients were mon-itored for around 54 months, until death, or the last known surviving data (range 20-60 months). A statistically significant relationship exists between COX-2 expression was sig-nificantly related to the old age group, tumour extent, relapse, mortality, and poor DFS; (p = 0.001), (p = 0.01), (p = 0.002), and (p = 0.035), respectively. While VEGF, ProEx-C, and TERT expression with the old age group, tumour extent, lymph node metastasis, advancedstaging, relapse, mortality, poor disease free sur-vival (DFS), and overall survival (p = 0.001). Human papillomavirus-related multiphenotypic sinonasal carcinoma is a unique sinonasal neoplasm with a strong link to HR-HPV strains. Expression of COX-2, VEGF, EGFR, ProEx-C, TERT was linked to poor prognosis, survival, and aggres-sive malignant behaviours such as proliferation, local recurrence, and lymph node metastasis, making them novel beneficial biomarkers and targeted therapies for HMSC patients.