Novel Therapeutic Strategies for HPV-Related Cancers

Human papillomavirus (HPV) is a DNA virus implicated in various oncogenic diseases and represents a major global public health concern. Although prophylactic vaccines are highly effective in preventing new infections, there are currently no curative therapies for persistent infections and HPV-associated malignancies. This thesis investigates innovative therapeutic strategies based on DNA immunotherapy and the use of novel pharmacological compounds, including small molecules targeting the viral E1 protein and a natural bioactive nutraceutical. The immunotherapeutic efficacy of DNA vaccines was assessed in murine models, evaluating both intratumoral administration and a linear DNA formulation. These approaches led to enhanced antigen-specific immune responses and significant tumor burden reduction. In parallel, in vitro studies evaluated the activity of in silico–selected small molecules and a standardized Tomato–Olive Bioactive Compound (TOBC), demonstrating their ability to inhibit HPV persistence and modulate key oncogenic signaling pathways. Overall, the results support the integration of immunological and pharmacological approaches as a promising strategy against HPV-driven diseases.