Tumor Infiltrating Lymphocytes (TILs) and T Cell Fraction in Human Papillomavirus (HPV) Associated Oropharyngeal Squamous Cell Carcinoma

Abstract

Purpose/Objective(s)The percentage of tumor infiltrating lymphocytes (TILs) is indicative of immune response and prognostic in many malignancies, although TILs data within HPV associated oropharyngeal cancer are limited. Our prior analyses of HPV associated malignancy revealed that both a higher fraction of T cells (TCF) to total cells present in the primary tumor specimen and a higher percentage of TILs were associated with a decreased chance of cancer recurrence. Herein, we investigated the relationship between these two immune related prognostic factors, TILs and TCF.Materials/MethodsPatients had HPV(+) oropharyngeal cancer and underwent primary surgery between 2007 and 2016. One representative H&E slide of the primary tumor was independently reviewed by two pathologists blinded to outcome for TILs count and presence/absence of desmoplastic stroma. The Brandwein-Gensler pattern of invasion (POI) score was used to grade the primary tumor. For TCF, immunosequencing of the CDR3 regions of human TCRβ chains was performed using an immunosequencing assay. TCF was determined as the proportion of T cells compared to the total number of nucleated cells in a sample. The TCF for patients by primary tumor TILs density, desmoplastic stroma, and POI were evaluated using Wilcoxon rank sum tests.ResultsTwenty-four patients were identified who had both TCF and TILs count available for comparison. Median age was 55 years (IQR 47-61), 96% were male, 42% had a > 10 pack year history of smoking, and 83% underwent adjuvant therapy. For patients with < 10% TILS, median TCF was 0.29 (IQR 0.17-0.36) as compared to TCF of 0.40 (IQR 0.34-0.57) for patients with ≥10% TILs (P = 0.09). There was no statistically significant difference (P = 0.5) in TCF for patients with desmoplastic stroma absent (median TCF 0.41; IQR 0.36-0.48) versus desmoplastic stroma present (median TCF 0.34; IQR 0.23-0.50). Patients with POI I or II had similar TCF to those with type III or IV, median TCF 0.37 (IQR 0.30-0.48) versus 0.35 (IQR 0.23-0.50), respectively (P = 0.8).ConclusionIn this series of HPV+ oropharyngeal cancer patients, TILs ≥10% was associated with a higher fraction of T cells to total cells (TCF) (n = 24, P = 0.09). Additional investigation is warranted including the relationship of TCF as characterized by sequencing and pathologist quantification of TILs, and whether the combination of these factors improves prognostication over each alone. The percentage of tumor infiltrating lymphocytes (TILs) is indicative of immune response and prognostic in many malignancies, although TILs data within HPV associated oropharyngeal cancer are limited. Our prior analyses of HPV associated malignancy revealed that both a higher fraction of T cells (TCF) to total cells present in the primary tumor specimen and a higher percentage of TILs were associated with a decreased chance of cancer recurrence. Herein, we investigated the relationship between these two immune related prognostic factors, TILs and TCF. Patients had HPV(+) oropharyngeal cancer and underwent primary surgery between 2007 and 2016. One representative H&E slide of the primary tumor was independently reviewed by two pathologists blinded to outcome for TILs count and presence/absence of desmoplastic stroma. The Brandwein-Gensler pattern of invasion (POI) score was used to grade the primary tumor. For TCF, immunosequencing of the CDR3 regions of human TCRβ chains was performed using an immunosequencing assay. TCF was determined as the proportion of T cells compared to the total number of nucleated cells in a sample. The TCF for patients by primary tumor TILs density, desmoplastic stroma, and POI were evaluated using Wilcoxon rank sum tests. Twenty-four patients were identified who had both TCF and TILs count available for comparison. Median age was 55 years (IQR 47-61), 96% were male, 42% had a > 10 pack year history of smoking, and 83% underwent adjuvant therapy. For patients with < 10% TILS, median TCF was 0.29 (IQR 0.17-0.36) as compared to TCF of 0.40 (IQR 0.34-0.57) for patients with ≥10% TILs (P = 0.09). There was no statistically significant difference (P = 0.5) in TCF for patients with desmoplastic stroma absent (median TCF 0.41; IQR 0.36-0.48) versus desmoplastic stroma present (median TCF 0.34; IQR 0.23-0.50). Patients with POI I or II had similar TCF to those with type III or IV, median TCF 0.37 (IQR 0.30-0.48) versus 0.35 (IQR 0.23-0.50), respectively (P = 0.8). In this series of HPV+ oropharyngeal cancer patients, TILs ≥10% was associated with a higher fraction of T cells to total cells (TCF) (n = 24, P = 0.09). Additional investigation is warranted including the relationship of TCF as characterized by sequencing and pathologist quantification of TILs, and whether the combination of these factors improves prognostication over each alone.