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

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 infiltrating 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 significantly higher levels of CD8+ tumor infiltrating lymphocytes (p<0.05) and higher levels of PD-L1 expression (p<0.05). CONCLUSION: Exposure to chemo-radiation and recurrence following treatment preserves critical features of intrinsic tumor biology and the tumor immune microenvironment suggesting that novel treatment regimens may be as effective in the salvage setting as in the definitive intent setting.