Integrating Immunotherapy, Novel Agents, and Their Combinations with Standard Treatments in the Management of Head and Neck Cancers

Dear Colleagues,

Head and neck cancers are very heterogeneous, and the majority of these cancers are squamous cell carcinomas (HNSCCs) related to long-term smoking and alcohol intake. However, there has been an increasing incidence of oropharyngeal cancers due to human papillomavirus (HPV) infection. The HPV-induced oropharyngeal SCCs have a different biology to HPV-negative HNSCCs, and patients with these tumors respond better to chemoradiation and have a better prognosis. As a result, there have been several strategies to de-escalate treatments for these patients in order to reduce the long-term toxicities from chemoradiation. However, de-escalation using cetuximab replacing cisplatin chemotherapy has shown inferior survival outcomes without reducing acute and long-term toxicities. Therefore, it remains an open question how best to de-escalate treatment for these HPV oropharyngeal cancers. Could immunotherapy or other novel agents sensitize to radiotherapy to ensure equivalent or better outcomes than with chemoradiation in these patients? In addition, certain patients present with very aggressive tumors and the disease relapses or progresses soon after radiotherapy or chemoradiation, suggesting a benefit from treatment intensification.

Could immunotherapy or novel agents be integrated as part of the standard treatments, and if so, how would it be best to combine these treatments (concurrent versus sequential)? A fundamental understanding of how these tumors behave and respond to different treatments would be key to achieving optimum treatment combination with minimal toxicities.

An anti-PD1 checkpoint inhibitor is now approved as a first-line and second-line treatment in recurrent and metastatic HNSCC, and it has recently been established as a component of curative-intent treatment for patients with advanced resectable HNSCC. Nevertheless, several important questions remain unanswered, including the optimal role and duration of adjuvant immunotherapy, whether additional chemotherapy provides benefit in unresectable or inoperable disease, and whether the KEYNOTE-689 approach is appropriate for high-risk HPV-related tumors as well as for laryngeal and hypopharyngeal cancers. In addition, multiple novel agents including targeted therapies and immunotherapy are being tested in clinical trials, and how these agents would eventually fit in with the treatment pathways in HNSCC remains to be elucidated. Lastly, biomarker-driven clinical studies based on genetic aberrations have shown great promise and intensified interest, but the results have, to date, been disappointing. It is possible that an optimum treatment combination to prevent drug resistance and the incorporation of immunotherapy may improve the outcomes of patients treated with therapies targeted against specific genomic aberrations.

We are pleased to invite you to contribute to this Special Issue on the biology, rationale, and preclinical and clinical evidence on the optimum treatment combination of immunotherapy and novel agents with radiotherapy and/or chemotherapy to improve the treatment outcomes in head and neck cancers. We welcome high-quality review and original research articles covering basic, translational, and clinical studies related to these areas in head and neck cancers.

Prof. Dr. Jan B. Vermorken
Dr. Petr Szturz
Prof. Dr. Kevin Harrington
Dr. Laurent Muller
Guest Editors

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• head and neck cancer
• oropharyngeal cancer
• chemotherapy
• immunotherapy
• biomarker
• targeted therapies
• checkpoint inhibitor