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Review

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

  • Authors:
    • Xiaojing Zhou
    • Ren An
    • Xiangjuan Li
  • View Affiliations / Copyright

    Affiliations: Department of The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, Department of Clinical Medicine, Clinical Medical College, Hangzhou Normal University, Hangzhou, Zhejiang 311121, P.R. China, Department of Obstetrics and Gynecology, Affiliated Hangzhou Women's Hospital, Hangzhou, Zhejiang 310008, P.R. China
  • Article Number: 22
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    Published online on: November 5, 2025
       https://doi.org/10.3892/ol.2025.15375
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Abstract

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.
View Figures

Figure 1

Mechanisms of HPV-mediated immune
evasion in cervical cancer. HPV oncoproteins E5, E6 and E7
orchestrate multi-level immune evasion. E6 and E7 inhibit the IRF3,
STAT1 and the STING-cGAS signaling pathways, suppressing type I
interferon signaling. E5 downregulates MHC-I while maintaining
HLA-C/E to avoid NK cells. E6 and E7 impair DC maturation and
antigen presentation. Together, these oncoproteins remodel the TIME
by upregulating IL-10, TGF-β and PD-L1, inducing Treg and M2
macrophage accumulation, enhancing IDO1-mediated tryptophan
catabolism and promoting immune tolerance. Collectively, these
processes establish an immunosuppressive TIME that facilitates
viral persistence and tumor progression (38–49,64).
IDO, indoleamine 2,3-dioxygenase; STING, stimulator of interferon
genes; HPV, human papillomavirus; IRF3, interferon regulatory
factor-3; cGAS, cyclic GMP-AMP synthase; MHC-1, major
histocompatibility complex class I; HLA, human leukocyte antigen;
NK, natural killer; PD-L1, programmed death-ligand 1; Treg,
regulatory T cell; TIME, tumor immune microenvironment; pDC,
plasmacytoid dendritic cell.
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Copy and paste a formatted citation
Spandidos Publications style
Zhou X, An R and Li X: Cervical cancer immune microenvironment: Mechanisms of HPV‑mediated immune evasion and advances in immunotherapy (Review). Oncol Lett 31: 22, 2026.
APA
Zhou, X., An, R., & Li, X. (2026). Cervical cancer immune microenvironment: Mechanisms of HPV‑mediated immune evasion and advances in immunotherapy (Review). Oncology Letters, 31, 22. https://doi.org/10.3892/ol.2025.15375
MLA
Zhou, X., An, R., Li, X."Cervical cancer immune microenvironment: Mechanisms of HPV‑mediated immune evasion and advances in immunotherapy (Review)". Oncology Letters 31.1 (2026): 22.
Chicago
Zhou, X., An, R., Li, X."Cervical cancer immune microenvironment: Mechanisms of HPV‑mediated immune evasion and advances in immunotherapy (Review)". Oncology Letters 31, no. 1 (2026): 22. https://doi.org/10.3892/ol.2025.15375
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou X, An R and Li X: Cervical cancer immune microenvironment: Mechanisms of HPV‑mediated immune evasion and advances in immunotherapy (Review). Oncol Lett 31: 22, 2026.
APA
Zhou, X., An, R., & Li, X. (2026). Cervical cancer immune microenvironment: Mechanisms of HPV‑mediated immune evasion and advances in immunotherapy (Review). Oncology Letters, 31, 22. https://doi.org/10.3892/ol.2025.15375
MLA
Zhou, X., An, R., Li, X."Cervical cancer immune microenvironment: Mechanisms of HPV‑mediated immune evasion and advances in immunotherapy (Review)". Oncology Letters 31.1 (2026): 22.
Chicago
Zhou, X., An, R., Li, X."Cervical cancer immune microenvironment: Mechanisms of HPV‑mediated immune evasion and advances in immunotherapy (Review)". Oncology Letters 31, no. 1 (2026): 22. https://doi.org/10.3892/ol.2025.15375
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