Immunotherapy in Head and Neck Cancer When, How, and Why?

Head and neck cancer (HNC) is one of the most common cancers worldwide. Alcohol and tobacco consumption, besides viral infections, are the main risk factors associated with this cancer. When diagnosed in advanced stages, HNC patients present a higher probability of recurrence or metastasising. The complexity of therapeutic options and post-treatment surveillance is associated with poor prognosis and reduced overall survival (OS). This review aims to explore immunotherapy (immune checkpoint inhibitors (ICI), therapeutic vaccines, and oncolytic viruses) in HNC patients' treatment, and to explore when, how, and why patients can benefit from it. The monotherapy with ICI or in combination with chemotherapy (QT) shows the most promising results. Compared to standard therapy, ICI are able to increase OS and patients' quality of life. QT in combination with ICI demonstrates significant response rates and considerable long-term clinical benefits. However, the toxicity associated with this approach is still a hurdle to overcome. In parallel, the therapeutic vaccines directed to the Human Papilloma Virus are also efficient in increasing the antitumour response, inducing cellular and humoral immunity. Although these results demonstrate clinical benefits compared to standard therapy, it is also important to unravel the resistance mechanisms in order to predict the clinical benefit of immunotherapy.