Bulletin of Stomatology and Maxillofacial Surgery
ISSN 1829-006X
2025; 128–143
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TGF-β SIGNALING IN HPV-POSITIVE HEAD AND NECK CANCER: FROM EARLY TUMOR SUPPRESSION TO METASTASIS AND RESISTANCE

Gaurav Gupta*

Received: 2026-04-08 · Published: 2025-05-18

© 2025 The Author(s) and the original publisher.

CC BY-NC 4.0 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
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Original title
TGF-β SIGNALING IN HPV-POSITIVE HEAD AND NECK CANCER: FROM EARLY TUMOR SUPPRESSION TO METASTASIS AND RESISTANCE
Author
Gaurav Gupta
Source journal
Bulletin of Stomatology and Maxillofacial Surgery
Published
2025-05-18
Licence
Creative Commons Attribution-NonCommercial 4.0 International
Original
https://doi.org/10.58240/1829006X-2025.21.4-128

Abstract

The TGF-β signalling pathway is an enigmatic player with a tumor suppressor effect in HPV-positive head and neck cancer during the initial stages of cancer, but has a pro-cancer effect during later stages. Specifically, HPV-positive oropharyngeal carcinomas are characterized by the suppression of TGF-β signalling due to the virus's changes in the cells. In the initial stage of cancer, TGF-β works pro-apoptotic and anti-proliferative, while in the later stages, it is involved in immune checkpoint, metastasis, and chemoresistance. This duality presents major problems for therapeutic intervention as modulation of the tumor-promoting effects of TGF-β requires sparing its tumorsuppressing properties. However, recent studies have reported novel therapeutic approaches such as selective inhibitors, immune checkpoint blockade, and combined targeted therapy for HPV oncoproteins and the TGF-β pathway. These approaches present some promise for enhancing clinical results; however, more research is required to realize these benefits for the benefit of the patients. This review examines the complex role of TGF-β signalling in HPV-positive head and neck cancers and discusses its implications for future therapeutic development.
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