Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with a mortality of more than 50%. It arises from the squamous lining of the mucosal surfaces of the upper aerodigestive tract. Despite the existence of effective available treatments, failure to cure and recurrence are common and account for the majority of deaths. Tumor microenvironment (TME) plays a critical role in tumorigenesis, that is, initiation, progression, and metastasis of HNSCC. A dynamic TME not only promotes systemic tumorigenesis but also significantly modifies therapeutic responses and prognosis. Fundamental TME factors, together with tumor-non-tumor microenvironmental interactions, represent potential points of intervention for therapeutic strategies against HNSCC.

This special issue invites authors to submit their original research and review articles that focus on the cellular and molecular components of the TME, with a particular focus on head and neck cancer. The issue aims to collect submissions employing cutting-edge science with important implications for the prevention, diagnosis, and treatment of head and neck cancer. The issue also aims to cover the characterization of the molecular profile of the TME and cytopathological changes of cancers at different tumor stages. Studies of new drugs and biological agents that target the TME will also be considered. The issue highly encourages the use of cell lines as well as animal models to support findings.

Potential topics include but are not limited to the following:

• Impact of TME on genomic stability and DNA repair in HNSCC
• Regulation of gene expression in the HNSCC microenvironment
• Innate and adaptive immunity in the HNSCC microenvironment
• Interplay between cytopathological changes and TME in HNSCC
• Targeting TME of head and neck cancer using immunotherapy and new drugs
• Advancement in natural product research targeting TME