Abstract A07: Improved prognosis of HPV-positive oropharyngeal cancers is associated with a suppression of TGF-β-mediated immune evasion

Abstract

Abstract Among head and neck squamous carcinoma (HNSC), human papilloma virus (HPV)-driven tumors are known to enjoy more favorable prognostic outcomes compared to non-HPV-driven disease. This is especially true of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), which is associated with significantly improved outcomes compared to HPV-positive non-OPSCC and HPV-negative HNSC. Previous reports have suggested that increased immune infiltration and expression of the estrogen receptor α (ERα) may play a role in conferring improved prognosis to HPV-positive OPSCC. However, the underlying signaling pathways specifically driven by HPV in the oropharynx have remained elusive. Here we analyzed HPV-positive OPSCC and non-OPSCC tumors from The Cancer Genome Atlas (TCGA) and found that HPV-positive OPSCC is associated with significantly improved overall and disease-specific survival and progression-free interval compared to HPV-positive non-OPSCC. Among HPV-positive HNSC, we observed a distinct separation of OPSCC from non-OPSCC tumors based on unsupervised clustering of gene expression, microRNA, and methylation profiling data. Separation based on anatomic site was not observed among HPV-negative HNSC, suggesting that common biology drives the carcinogenesis of HPV-negative HNSC across subsites. In line with a recent report that ERα mRNA expression is elevated HPV-positive OPSCC, we found significantly higher ERα mRNA levels in HPV-positive OPSCC compared to HPV-positive non-OPSCC, where ERα mRNA expression mirrored that in HPV-negative HNSC. We also found that HPV induces downregulation of TGF-β signaling and extracellular matrix (ECM)-associated genes while upregulating a T-cell and dendritic cell-associated immune response signature in an OPSCC-specific manner. Our analyses suggest that HPV induces downregulation of TGF-β signaling and ECM components in OPSCC to improve immune access to these tumors, facilitating tumor clearance and improved patient survival. These findings are in line with our recent report establishing TGF-β-mediated immunosuppression through ECM deregulation and its negative effect on patient prognosis. Citation Format: Anthony Bolyos, Pinaki Bose. Improved prognosis of HPV-positive oropharyngeal cancers is associated with a suppression of TGF-β-mediated immune evasion [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A07.