Programmed Cell Death Ligand 1 Immunoexpression in Head and Neck Squamous Cell Carcinoma: A Narrative Review of Considerations for the Histopathologist

Abstract

Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common malignancies worldwide with most of the patients presenting in advanced stage. The associated high mortality and poor prognosis of the tumour has rendered the search for better therapeutic options than the traditional modalities of surgery, radiotherapy and chemotherapy. Immunotherapy targeting Programmed Cell Death Protein 1 / Programmed Cell Death Ligand 1 (PD-1/PD-L1) has been approved in recurrent/ metastatic HNSCC cases. PD-L1 expressing HNSCCs are likely to respond to immunotherapy. PD-L1 expression has been studied in peripheral blood utilising Circulating Tumour Cells (CTC) and soluble exosomes. Despite these non invasive techniques, PD-L1 expression has been most frequently assessed by immunohistochemistry (IHC) application on the Formalin Fixed Paraffin Embedded (FFPE) tissue of the tumour. Currently, many antibody clones and various IHC platforms are available for PD-L1, but only 22c3 has been approved by the Food and Drug Administration (FDA). Although, the availability of multiple options has made PD-L1 assessment possible and affordable at many centres worldwide, but various procedural, pre-analytical, and analytic issues have to be considered prior to the interpretation of immunoexpression of PD-L1. In this review, the authors aim to highlight the problem areas, and to understand the implications of PD-L1 expression in HNSCC. The authors propose recommendations for the optimal assessment of PD-L1 expression in HNSCC on IHC.