HPV E6 oncoprotein in cancer pathogenesis and therapeutic targeting: molecular mechanisms and emerging strategies

Certain high-risk strains of human papillomavirus (HPV), particularly HPV16 and HPV18, are closely linked to cancer development. Understanding how the E6 oncoprotein interacts with host cell factors, particularly tumor suppressors like p53, can shed light on the mechanisms of malignant transformation and help identify potential biomarkers for early detection. Biochemical and cellular studies suggest genotype-dependent differences in the interaction of E6 with p53 and E6AP; however, the magnitude and biological significance of these differences appear to depend on the experimental system. E6 promotes uncontrolled cell growth by targeting tumor suppressors, particularly p53, disrupting cell cycle control, inhibiting apoptosis, and impairing multiple tumor-suppressive pathways. Current medical strategies to aim to halt disease progression and enhance immune recognition by neutralizing E6. This review explores the molecular functions of E6, focusing on its role in tumorigenesis and the ability to disrupt key tumor-suppressor pathways. We also highlight therapeutic strategies that target these oncogenic mechanisms for the prevention and treatment of HPV-driven malignancies.