Beyond conventional therapies: immunotherapeutic strategies targeting HPV-associated cervical cancer

Cervical cancer continues to represent a significant global health challenge, primarily due to persistent infection with high-risk human papillomavirus (HPV) types. While prophylactic HPV vaccines have substantially reduced infection rates, their inability to address established infections or HPV-driven malignancies highlights a critical therapeutic gap. Conventional treatment modalities, such as chemotherapy, radiotherapy, and surgery remain the cornerstone of cervical cancer management; however, these approaches are often associated with nonspecific toxicity, diminished quality of life, treatment resistance, and elevated recurrence rates. Notably, conventional therapies are not specifically designed to target persistent HPV infection, and viral clearance may not be consistently achieved. This narrative review synthesizes studies retrieved from PubMed, Scopus, Web of Science, and Google Scholar published up to March 2026. It critically evaluates the limitations of current therapeutic strategies and emphasizes emerging non-conventional immunotherapeutic approaches designed to address HPV persistence and tumor immune evasion. Particular attention is given to nanocarrier-based therapeutic platforms, siRNA-mediated E6/E7 silencing and CRISPR-based disruption of the HPV genome, are presented as promising methods for precise molecular intervention. Additionally, advances in therapeutic vaccines, immune checkpoint inhibition, and γδ T-cell-based immunotherapy are also explored as potential strategies to restore HPV-specific immune surveillance and achieve sustained clinical responses.