A Review of Immunotherapy for Head and Neck Cancer

Abstract

The introduction of immune checkpoint inhibitors (ICIs) to oncological care has transformed the management of various malignancies, including head and neck squamous cell carcinoma (HNSCC), offering improved outcomes. The first-line treatment of recurrent and malignant HNSCC for many years was combined platinum, 5-fluorouracil, and cetuximab. Recently, the ICI pembrolizumab was approved as a first-line treatment, with or without chemotherapy, based on tumor and immune cell percentage of programmed-death ligand 1 (PD-L1). Multiple head and neck (HN) cancer trials have subsequently explored immunotherapies in combination with surgery, chemotherapy, and/or radiation. Immunotherapy regimens may be personalized by tumor biomarker, including PD-L1 content, tumor mutational burden, and microsatellite instability. However, further clinical trials are needed to refine biomarker-driven protocols and standardize pathological methods to guide combined regimen timing, sequencing, and deescalation. Gaps remain for protocols using immunotherapy to reverse oral premalignant lesions, particularly high-risk leukoplakias. A phase II nonrandomized controlled trial, using the ICI nivolumab, showed a 2-y cancer-free survival of 73%, although larger trials are needed. Guidelines are also needed to standardize the role of dental evaluation and care before, during, and after immunotherapy, specifically in regard to oral immune-related adverse events and their impact on cancer recurrence. Standardized diagnostic and oral care coordination strategies to close these gaps are needed to ensure continued success of HN cancer immunotherapy.

Keywords: biomarkers; cancer vaccines; human papillomavirus viruses; immune checkpoint inhibitors; precision medicine; tumor microenvironment.

Figure 1.

Immune checkpoint inhibitors and associated adverse events. Abbreviations: CD80, cluster of differentiation 80; CTLA-4, cytotoxic T lymphocyte–associated protein 4; IL-10, interleukin 10; MHC I, major histocompatibility complex 1; PD-1, programmed death protein 1; PD-L1, programmed death protein ligand 1; SS, Sjögren’s syndrome; TCR, t-cell receptor; T-reg cell, T-regulatory cell; TGF-β, transforming growth factor–beta.