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Application of mRNA vaccines in head and neck cancer immunotherapy: Current progress and challenges

Linrong Wu1, Hongshuai Liu1, Zhikai Wang2

  • 1Department of Otolaryngology-Head and Neck Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang Province 315000, PR China; Ningbo Key Laboratory of Digital Medicine Precision Diagnosis and Treatment of Otorhinolaryngology, Head and Neck Diseases, Ningbo, Zhejiang Province 315000, PR China.

Critical Reviews in Oncology/Hematology
|July 28, 2026
PubMed

Insights

Messenger RNA (mRNA) vaccines show promise for head and neck cancer (HNC) immunotherapy by targeting tumor antigens and overcoming treatment resistance. Personalized neoantigen vaccines demonstrate improved survival, especially in HPV-positive cases.

Area of Science:

  • Oncology
  • Immunotherapy
  • Vaccine Technology

Background:

  • Head and neck cancer (HNC) presents a significant global health challenge with limited efficacy from conventional treatments due to immunosuppressive tumor microenvironments and heterogeneity.
  • While immune checkpoint inhibitors (ICIs) show some success in recurrent/metastatic HNC, modest response rates and resistance necessitate novel therapeutic strategies.
  • Messenger RNA (mRNA) vaccines offer a flexible and rapid approach to induce potent, antigen-specific immune responses, making them a promising avenue for HNC immunotherapy.

Purpose of the Study:

  • To comprehensively review the application of mRNA vaccines in head and neck cancer (HNC) immunotherapy.
  • To analyze different antigen sources (tumor-associated antigens, tumor-specific neoantigens, virus-associated antigens) and delivery platforms (lipid nanoparticles, self-amplifying RNA, dendritic cell-mRNA vaccines).
  • To discuss the integration of mRNA vaccines with other treatment modalities and identify future research directions.

Main Methods:

  • Review of preclinical and clinical data on mRNA vaccine applications in HNC.
  • Analysis of various antigen sources including TAAs, TSAs, and HPV antigens (E6/E7).
  • Evaluation of diverse delivery platforms such as LNPs, saRNA, and DC-mRNA vaccines.

Main Results:

  • Personalized neoantigen mRNA vaccines can induce robust T-cell responses and improve survival, particularly in HPV-positive head and neck squamous cell carcinoma (HNSCC).
  • Combination strategies involving mRNA vaccines with ICIs, chemotherapy, or radiation therapy are being explored.
  • Challenges include tumor heterogeneity, delivery inefficiency, immunosuppressive TME, manufacturing complexity, and lack of predictive biomarkers.

Conclusions:

  • mRNA vaccines hold significant potential to revolutionize HNC treatment by offering durable immune protection and improved clinical outcomes.
  • Further research is needed to overcome current challenges, including the development of 'off-the-shelf' vaccines, advanced delivery systems, and biomarker-guided patient selection.
  • Continued innovation in mRNA technology and translational research is crucial for the widespread clinical translation of these therapies.
Keywords:
Head and neck cancerImmune checkpoint inhibitorMRNA vaccineNeoantigenPersonalized immunotherapy

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