CTLA4 genetic variants influence immune regulation and susceptibility of HPV associated cervical cancer

Cervical cancer remains a significant global health burden, representing one of the leading causes of morbidity and mortality among women. While persistent infection with oncogenic types of Human Papillomavirus (HPV) is the primary risk factor for cervical carcinogenesis, only a subset of infected women progress to malignancy, suggesting that host genetic factors play a critical role in disease susceptibility. This narrative review explores the influence of single nucleotide variants (SNVs) in the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) on the risk of HPV-associated cervical cancer, with a focus on the modulation of this immune checkpoint pathway. CTLA-4 is expressed on the surface of T cells and functions as a negative regulator of immune activation. Its genetic variants may influence gene transcription efficiency, protein processing and transport, and/or binding affinity to its B7 ligand, thereby affecting viral clearance and immune surveillance against HPV-transformed cells. Current evidence supports associations between specific CTLA4 SNVs, such as rs5742909 (- 318 C > T), rs231775 (+ 49 A > G) and rs3087243 (+ 6230 G > A), and increased susceptibility to cervical cancer, supporting their potential as prognostic biomarkers and therapeutic targets in cancer immunotherapy. These findings highlight the relevance of host genetics in the personalized management of cervical cancer.