Immunotherapy in head and neck squamous cell carcinoma: An updated review

Highlights

• There are growing efforts to characterize the tumor microenvironment of head and neck squamous cell carcinoma (HNSCC) in order to carefully select patients and use feasible biomarkers to gain maximum benefit from available therapies.

• Immune checkpoint inhibitors (ICI) are used not only in the second-line recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) setting, but also recently based on results from KEYNOTE-048, ICI has been approved in the first line setting for R/M HNSCC. Their role in locally advanced HNSCC in neoadjuvant setting to allow reduced chemotherapy/radiotherapy is promising.

• It has been postulated that the improved outcomes in HPV-positive cancers may be related to increased sensitivity to therapy or enhanced anti-tumor immunity. In KEYNOTE-012 and HAWK trials, patients with HPV1 disease had higher response rates than patients with HPV negative disease when treated with ICI therapy. Conversely, in KEYNOTE-040, KEYNOTE 055 HPV- cancers appeared to have greater benefit. Optimal patient selection for de‐escalation strategy is therefore critically important.

• Data on other novel forms of immunotherapy like CAR-T cell, oncolytic virus therapy, and vaccines is emerging in HNSCC either alone or in combination with other therapies.

Abstract

Squamous cell cancer of the head and neck (HNSCC) is the sixth most common cancer and is associated with significant morbidity and mortality. The tumor microenvironment for HNSCC is a complex interplay of immune cells, stromal cells, and cytokines amongst others. Immunotherapy acts as an effective antineoplastic agent by influencing this complex environment and includes immune checkpoint inhibitors (ICI). ICI have been approved in the frontline setting for recurrent and metastatic (R/M) HNSCC as well as platinum-refractory (second line) R/M HNSCC. However, recent clinical studies highlight that the response to immunotherapy varies, and different ICI, as well as different combination strategies play a crucial role in augmenting the efficacy of immunotherapy. An in-depth analysis and focused study of the immune contexture in patients with HNSCC receiving ICI remains critical. Many novel immunotherapies including CAR-T cell therapy, oncolytic virus therapy, and vaccines are underway. Ongoing trials are testing ICI in the neoadjuvant and adjuvant settings. Furthermore, identifying better biomarkers to target population that benefits from immunotherapy is of paramount importance. Pioneering the optimal combination regimen utilizing new novel immunotherapy has recently become a paradigm shift in the HNSCC treatment landscape. Herein, we summarize the clinical development with all ongoing clinical trials of immunotherapy in HNSCC.