Recurrent Oropharyngeal Squamous Cell Carcinomas Maintain Anti-tumor Immunity and Multinucleation Levels Following Completion of Radiation

Abstract

Objective: Oropharyngeal squamous cell carcinoma (OPSCC) recurrence is almost universally fatal.Development of effective therapeutic options requires an improved understanding of recurrent OPSCC biology.Methods: We analyzed paired primary-recurrent OPSCC from Veterans treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who received curative intent radiation-based treatment (with or without chemotherapy). Patient tumors were analyzed using standard immunohistochemistry and automated imaging of in ltrating lymphocytes and multinucleated tumor cells coupled to machine learning algorithms.Results:Primary and recurrent tumors demonstrated high concordance via p16 and p53 immunohistochemistry, with comparable levels of multinucleation. In contrast, recurrent tumors demonstrated signi cantly higher levels of CD8+ tumor in ltrating lymphocytes (p<0.05) and higher levels of PD-L1 expression (p<0.05).Conclusion: Exposure to chemo-radiation and recurrence following treatment does not appear deleterious to underlying biological characteristics and anti-tumor immunity of oropharyngeal cancer, suggesting that novel treatment regimens may be as effective in the salvage setting as in the de nitive intent setting.