Genome Editing Against HPV-Driven Cancers: From Bench to Clinic

Genome editing technologies including CRISPR/Cas9, TALENs, and ZFNs offer a unique opportunity to eradicate HPV by directly disrupting its oncogenes E6 and E7, thereby restoring tumour‑suppressor pathways. In this review, we provide a comprehensive overview of recent advances in HPV‑targeted genome editing, summarising key preclinical findings that demonstrate tumour regression and apoptosis in HPV‑positive models, as well as the first‑in‑human clinical trials assessing safety and feasibility of local CRISPR‑based therapies. We also compare the relative strengths and limitations of each editing platform, discuss delivery strategies, and highlight their potential integration with immunotherapy and standard cancer treatments. While genome editing shows unprecedented precision and durability in targeting viral oncogenes, challenges such as efficient delivery, minimising off‑target effects, and navigating regulatory and ethical considerations remain. Continued optimisation of high‑fidelity nucleases, tissue‑specific delivery vehicles, and personalised guide design will be essential to translate these promising approaches into routine oncology practice. Genome editing thus represents a paradigm shift in HPV therapy, with the potential to transform management of both persistent infections and established cancers.