Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased substantially over the past three decades, and since 2017, it has been recognized in the AJCC staging system as distinct from its HPV-negative counterpart. The underlying mechanisms of...

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Main Authors: Fangdi Sun, A. Dimitrios Colevas
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/5/712
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author Fangdi Sun
A. Dimitrios Colevas
author_facet Fangdi Sun
A. Dimitrios Colevas
author_sort Fangdi Sun
collection DOAJ
description The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased substantially over the past three decades, and since 2017, it has been recognized in the AJCC staging system as distinct from its HPV-negative counterpart. The underlying mechanisms of HPV-associated carcinogenesis, tumor microenvironment, and host immune response represent opportunities for therapeutic development. While anti-PD-1 immunotherapy is now part of standard treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in general, there are no established immunotherapeutic strategies specifically for HPV-related HNSCC. In this context, multiple emerging approaches are being actively studied—among these are therapeutic vaccines with or without anti-PD-(L)1 adjuvants, peptide–HLA-based immunotherapeutic platforms, and adoptive cell therapies including tumor-infiltrating lymphocytes (TILs), T-cell receptor (TCR) therapy, and chimeric antigen receptor (CAR) T-cell therapy. Beyond further maturation of these novel immunotherapeutic strategies, additional work is needed to delineate the optimal disease state of application (localized versus recurrent/metastatic), as well as in the development of small molecule inhibitors targeting HPV-specific mechanisms of viral oncogenesis.
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spelling doaj-art-8757c64f677d4a739e33e4fe0c99411b2025-08-20T03:47:58ZengMDPI AGViruses1999-49152025-05-0117571210.3390/v17050712Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell CarcinomaFangdi Sun0A. Dimitrios Colevas1Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USADivision of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USAThe incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased substantially over the past three decades, and since 2017, it has been recognized in the AJCC staging system as distinct from its HPV-negative counterpart. The underlying mechanisms of HPV-associated carcinogenesis, tumor microenvironment, and host immune response represent opportunities for therapeutic development. While anti-PD-1 immunotherapy is now part of standard treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in general, there are no established immunotherapeutic strategies specifically for HPV-related HNSCC. In this context, multiple emerging approaches are being actively studied—among these are therapeutic vaccines with or without anti-PD-(L)1 adjuvants, peptide–HLA-based immunotherapeutic platforms, and adoptive cell therapies including tumor-infiltrating lymphocytes (TILs), T-cell receptor (TCR) therapy, and chimeric antigen receptor (CAR) T-cell therapy. Beyond further maturation of these novel immunotherapeutic strategies, additional work is needed to delineate the optimal disease state of application (localized versus recurrent/metastatic), as well as in the development of small molecule inhibitors targeting HPV-specific mechanisms of viral oncogenesis.https://www.mdpi.com/1999-4915/17/5/712human papillomavirus (HPV)head and neck canceroropharyngeal cancersquamous cell carcinomaimmunotherapyimmune checkpoint inhibitor
spellingShingle Fangdi Sun
A. Dimitrios Colevas
Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma
Viruses
human papillomavirus (HPV)
head and neck cancer
oropharyngeal cancer
squamous cell carcinoma
immunotherapy
immune checkpoint inhibitor
title Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma
title_full Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma
title_fullStr Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma
title_full_unstemmed Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma
title_short Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma
title_sort update immunotherapeutic strategies in hpv associated head and neck squamous cell carcinoma
topic human papillomavirus (HPV)
head and neck cancer
oropharyngeal cancer
squamous cell carcinoma
immunotherapy
immune checkpoint inhibitor
url https://www.mdpi.com/1999-4915/17/5/712
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