Targeted Therapeutic Strategies for HPV-Associated Cancers: Molecular Mechanisms and Promising Approaches

Human papillomaviruses (HPVs) infect epithelial cells, causing transient or persistent infections, potentially leading to cancer. They evade immune surveillance by inhibiting pattern recognition receptors (PRRs) and antiviral signaling pathways. Current treatments for HPV-associated cancers have significant side effects, urging the need for alternative therapies. RIG-I agonist M8 shows promising anti-cancer activity in HPV- transformed cells, especially in combination with cisplatin, by inducing cell death and activating immune responses. Another approach involves the inhibition of SIRT1, a cellular deacetylase involved in HPV- induced transformation. SIRT1 inhibition resulted in restored p53 activity, impaired clonogenicity, and enhanced sensitivity to genotoxic agents in HPV+ cells. These findings suggest drug-targeted approaches against HPV-associated cancers, focusing on PRR activation or SIRT1 inhibition, as feasible alternatives to conventional therapies.