Virus-based gene therapy research Open access Peer reviewed

Oncolytic viruses in head and neck cancer: therapeutic promise and translational challenges

Haiting Wang, Hui Shen, Mingjun Zhang, Yakui Mou and 8 more

Frontiers in Immunology | Aug 28, 2026

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Developments support further exploration of OVs within biomarker-informed multimodal therapy for select patients of HNSCC, including that OVs selectively infect tumor cells, induce tumor cell lysis and immunogenic cell death, and modulate the tumor microenvironment.

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Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat, particularly in patients with HPV-negative disease. These patients often get diagnosed too late, their cancer doesn’t respond well to treatment, and they don’t live as long. Oncolytic viruses (OVs) can be used for treating cancer instead of using other cytotoxic methods since they can kill malignant cells directly and cause both local and systemic anti-cancer immune responses. In this review, we focus on current evidence of oncolytic virotherapy (OVT) in HNSCC, including that OVs selectively infect tumor cells, induce tumor cell lysis and immunogenic cell death, and modulate the tumor microenvironment. We also compare some OV platforms which were studied in HNSCC or similar solid-tumor settings: Herpes simplex virus (HSV), adenovirus, vaccinia virus, reovirus, measles virus, vesicular stomatitis virus, and Newcastle disease virus. Finally, we discuss emerging strategies to improve the efficacy and clinical translation of OVT for HNSCC, including tumor- or stimulus-responsive promoters, engineering of viral tropism and receptor specificity, modulation of both antiviral and immunosuppressive pathways, and incorporation between therapeutic payloads and advanced delivery systems. Altogether these developments support further exploration of OVs within biomarker-informed multimodal therapy for select patients of HNSCC.

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Authors

Researchers on this paper

Haiting Wang

first | Qingdao University

Hui Shen

middle | Qingdao University

Mingjun Zhang

middle | Qingdao University

Yakui Mou

middle | Qingdao University

Chao Ren

middle | Qingdao University

Yu Sun

middle | Qingdao University

Wanchen Liu

middle | Qingdao University

Caiyu Sun

middle | Qingdao University | ORCID 0000-0002-3001-5364

Dongxian Li

middle | Qingdao University | ORCID 0000-0003-0248-1584

Yumei Li

middle | Qingdao University | ORCID 0000-0003-3538-6268

Peng Qu

middle | Qingdao University | ORCID 0000-0002-0320-6288

Xicheng Song

last | Qingdao University

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Citation

BibTeX

@article{Wang2026Oncolytic,
  title = {Oncolytic viruses in head and neck cancer: therapeutic promise and translational challenges},
  author = {Haiting Wang and Hui Shen and Mingjun Zhang and Yakui Mou and Chao Ren and Yu Sun and Wanchen Liu and Caiyu Sun and Dongxian Li and Yumei Li and Peng Qu and Xicheng Song},
  journal = {Frontiers in Immunology},
  year = {2026},
  doi = {10.3389/fimmu.2026.1889008},
  url = {https://doi.org/10.3389/fimmu.2026.1889008}
}

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