Cervical cancer immune microenvironment: Mechanisms of HPV-mediated immune evasion and advances in immunotherapy (Review).

Cervical cancer, strongly associated with persistent infection by high-risk human papillomaviruses 16/18 (HPV 16/18), remains a major global health burden. The tumor immune microenvironment (TIME) of cervical cancer plays a decisive role in tumor progression and therapeutic outcomes, where HPV oncoproteins E5, E6 and E7 disrupt antigen presentation, interfere with interferon signaling, activate immune checkpoints and induce metabolic reprogramming, thereby establishing an immunosuppressive TIME. Therapeutic advances, including immune checkpoint inhibitors (e.g., pembrolizumab in KEYNOTE-826, nivolumab in CheckMate 358), therapeutic vaccines and adoptive cell therapies, have shown promise but face challenges such as low response rates, resistance, stromal barriers and microbiome-related influences. The aim of the present review is to summarize the current understanding of the cervical cancer TIME, elucidate HPV-mediated immune evasion mechanisms, and to highlight recent advances and ongoing challenges in immunotherapy. Future directions include combination strategies, novel immune targets, and precision approaches integrating spatial multi-omics and microbiota modulation, which may improve immunotherapy efficacy and support personalized treatments for cervical cancer.