Advancing Immunotherapy in Cervical Cancer: Biological Rationale, Clinical Evidence, and Biomarker Standardization

Abstract

Cervical cancer is strongly associated with persistent infection by high-risk human papillomavirus (HPV). Recent advances in immunotherapy have redefined the therapeutic landscape of this disease. We aim to review the biological rationale, clinical evidence, and biomarker standardization supporting the use of immune checkpoint inhibitors (ICIs) in cervical cancer. A comprehensive review of recent literature and pivotal phase II–III clinical trials was performed, focusing on the PD-1/PD-L1 and CTLA-4 pathways, mechanisms of immune evasion, and predictive biomarkers. Persistent HPV infection leads to immune dysregulation and PD-L1 upregulation through E6/E7-mediated activation of the PI3K/AKT/mTOR and JAK/STAT pathways. ICIs have demonstrated significant improvements in overall survival, progression-free survival, and objective response rates in advanced and recurrent disease. PD-L1 immunohistochemistry using standardized assays such as 22C3 pharmDx and SP263 remains the key biomarker for treatment selection, while emerging molecular markers (TMB, MSI, HLA-I expression) are under investigation. Immunotherapy represents a major step forward in cervical cancer management, integrating molecular diagnostics and immune modulation into clinical practice. Continued efforts to refine biomarkers, optimize combination strategies, and expand global access will be essential to achieve equitable outcomes and disease elimination goals.