Pd1 and Pdl1 in Hpv + and Hpv -/Tp53 Mutated Head and Neck Squamous Cell Carcinomas

Abstract

ABSTRACT Aim: The role of the programmed death 1 (PD1) and programmed death ligand 1 (PDL1) immunomodulatory axis in head and neck squamous cell carcinoma (HNSCC), a cancer with viral and non-viral etiologies, is investigated. Determination of the impact of this testing in human papilloma virus (HPV)-positive and HPV–negative/TP53-mutated HNSCC carries great importance due to the development of new immunomodulatory agents. Methods: Thirty-four HNSCC cases, including 16 HPV + and 18 HPV -/TP53 mut, were analyzed for the PD1/PDL1 immunomodulatory axis by immunohistochemical methods. HNSCC arising in the following anatomic sites were assessed: pharynx, larynx, mouth, parotid gland, paranasal sinuses, tongue and metastatic SCC consistent with head and neck primary. Results: 8/34 (24%) HNSCC were positive for tumor cell expression of PDL1, and 13/34 (38%) HNSCC were positive for PD1+ tumor infiltrating lymphocytes (TILs). 3/34 (8.8%) were positive for both components of the PD1/PDL1 axis. Comparison of PD1 and PDL1 expression in HPV + and HPV-/TP53 mut HNSCC showed PD1 + TILs were more frequent in HPV + vs. HPV–(56% vs. 22%; p = 0.07), whereas PDL1 + tumor cells more frequent in HPV–vs. HPV + (38% vs. 13%; p = 0.14). PD1 and PDL1 were expressed in both oropharyngeal and non-oropharyngeal HNSCC: 33% vs. 39% for PD1 + TILs, and 11% and 33% for PDL-1. To examine the role of PD1 and PDL1 in progression of disease, expression was compared between metastatic and non-metastatic HNSCC. PD1 + TILs were detected in 45% of metastatic vs. 25% non-metastatic HNSCC (p = 0.29), and PDL1 was detected in 27% vs. 17% of metastatic vs. non-metastatic HNSCC. Interestingly, the three cases that were positive for both PD1 and PDL1, were metastatic HNSCC, including a tumor of the mandible which had metastasized to the bone of the arm, and two unknown primary consistent with head and neck primary, one metastatasized to the lymph nodes and the other metastasized to the lung. Conclusions: Immune evasion through the PD1/PDL1 axis is relevant to both viral (HPV) and non-viral (TP53) etiologies of HNSCC. Expression of the axis components is also prevalent across HNSCC tumor sites, and elevated expression of both PD1 and PLD1 was seen at a higher frequency in metastatic HNSCC. Disclosure: R. Feldman: I am employed by Caris Life Sciences; Z. Gatalica: Dr. Gatalica is employed by, and owns stock in Caris Life Sciences. All other authors have declared no conflicts of interest.