Emerging Therapeutic Approaches to Head and Neck Cancer

Dear Colleagues,

Head and neck cancers comprise a heterogeneous group of tumors with diverse genetic and molecular profiles. Despite new biological insights, the global survival rate for head and neck cancers has remained unchanged over 30 years, at just over 50% at 5 years. Recently, the KEYNOTE-689 and the NIVOPOST-OP trial represented a significant step forward, exploring the potential use of immune checkpoint inhibitors in locally advanced disease to improve long-term outcomes.

In the recurrent/metastatic setting, immune checkpoint inhibitors are currently being employed, but only a minority of patients derive benefits, underscoring the need for improved patient selection and novel therapeutic strategies. The tumor microenvironment poses a challenge in immunotherapy, as it is inherently immunosuppressed. Tumor-related factors, such as the infiltration of immunosuppressive cells (e.g., MDSCs, Tregs, and CAFs), hypoxia, and host-related elements such as viral infections (e.g., HPV; EBV), tobacco use, and chronic inflammation, in addition to treatment-induced effects, contribute to immunosuppression. Among these, hypoxia plays a key role by impairing T-cell function and promoting angiogenesis through the HIF-1α and VEGF pathways, ultimately contributing to a “cold” immune environment that limits the effectiveness of immunotherapy. Recent new treatments, including less invasive surgical approaches, vaccines, antibody–drug conjugates, bispecific antibodies and immunotherapy combinations, and new heavy-particle radiotherapy, have not yet demonstrated survival benefits. The absence of reliable predictive biomarkers continues to represent a major unmet clinical need, limiting our ability to tailor these new strategies effectively.

For this Special Issue, we invite original research, reviews, and clinical trial data focused on the biology of head and neck cancer subtypes and innovative treatment strategies aimed at improving outcomes.

Prof. Dr. Laura D. D. Locati
Dr. Daria Maria Filippini
Guest Editors

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• head and neck cancer
• HPV-related head and neck cancer
• EBV-related nasopharyngeal cancer
• prognostic biomarkers
• predictive biomarkers
• novel combinations
• tumor microenvironment