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

Lakshmi Thangavelu*, Gaurav Gupta, Muhammad Afzal, Ghala Alnuaimi, Ahsas Goyal, Kavita Goyal, A Rekha, Mohit Rana, Rakhi Mishra, Parteek Prasher, Sachin Singh

Saveetha Medical College and Hospital ,Saveetha Institute of Medical and Technical Sciences,Saveetha University ,Chennai, India · 2Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India · Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, 21442 Jeddah, Saudi Arabia · Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates · Institute of Pharmaceutical Research, GLA University, Mathura, UP, India · Department of Biotechnology, Graphic Era (Deemed to be University), Clement Town, Dehradun 248002, India · 7Dr .D.Y.Patil Medical College Hospital and Research Centre, Pimpri, Pune, India 8Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India · Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India · 9Noida Institute of Engineering and Technology (Pharmacy Institute), 19 Knowledge Park 2,Greater Noida, India · Department of Chemistry, University of Petroleum & Energy Studies, Energy Acres, Dehradun, 248007, India · 1School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India 12Sunway Biofunctional Molecules Discovery Centre (SBMDC), School of Medical and Life Sciences, Sunway University, Sunway, Malaysia

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
Authors
Lakshmi Thangavelu, Gaurav Gupta, Muhammad Afzal, Ghala Alnuaimi, Ahsas Goyal, Kavita Goyal, A Rekha, Mohit Rana, Rakhi Mishra, Parteek Prasher, Sachin Singh
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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