TGF-β SIGNALING IN HPV-POSITIVE HEAD AND NECK CANCER: FROM EARLY TUMOR SUPPRESSION TO METASTASIS AND RESISTANCE

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.