HPV+ve/-ve oral-tongue cancer stem cells: A potential target for relapse-free therapy

Abstract

The tongue squamous cell carcinoma (TSCC) is a highly prevalent head and neck cancer often associated with tobacco and/or alcohol abuse or high-risk human papillomavirus (HR-HPV) infection. HPV positive TSCCs present a unique mechanism of tumorigenesis as compared to tobacco and alcohol-induced TSCCs and show a better prognosis when treated. The poor prognosis and/or recurrence of TSCC is due to presence of a small subpopulation of tumor-initiating tongue cancer stem cells (TCSCs) that are intrinsically resistant to conventional chemoradio-therapies enabling cancer to relapse. Therefore, targeting TCSCs may provide efficient therapeutic strategy for relapse-free survival of TSCC patients. Indeed, the development of new TCSC targeting therapeutic approaches for the successful elimination of HPV^+ve/-ve TCSCs could be achieved either by targeting the self-renewal pathways, epithelial mesenchymal transition, vascular niche, nanoparticles-based therapy, induction of differentiation, chemoradio-sensitization of TCSCs or TCSC-derived exosome-based drug delivery and inhibition of HPV oncogenes or by regulating epigenetic pathways. In this review, we have discussed all these potential approaches and highlighted several important signaling pathways/networks involved in the formation and maintenance of TCSCs, which are targetable as novel therapeutic targets to sensitize/eliminate TCSCs and to improve survival of TSCC patients.

Keywords: HPV; Prognosis; Relapse-free survival; Tongue cancer stem cells; Tongue squamous cell carcinoma.

Graphical abstract

Fig. 1

Different therapeutic strategies for tongue cancer stem cell targeting. Strategies for CSC targeting based on specific molecular characteristics including targeting the signaling network, targeting the stemness markers, inhibiting the tumor microenvironment, targeting with nanoparticle-based therapy, sensitizing cancer stem cells with natural and synthetic compounds or induction of CSC differentiation including targeting epigenomic pathways and ABC transporter cassette proteins.