LAUSR

Human papillomaviruses (HPV) are among the most common viral causes of cancer; infections account for a majority of cervical squamous cell carcinomas and endocervical adenocarcinomas (CESCs) and oropharyngeal squamous cell carcinomas. HPV-positive cancers demonstrate well-established differences in histopathology and clinical outcome compared to HPV-negative cancers, yet the biological mechanisms underlying these differences are not fully characterized. In this analysis, we highlight key pathways and candidate targets differentially expressed in HPV-positive head and neck squamous cell carcinomas (HNSCCs) and CESCs and investigate potential contributors to these differences, including microRNA (miRNA). Methods: We conducted an analysis of mRNA and protein expression in HPV-positive and HPV-negative HNSCCs and CESCs from the Cancer Genome Atlas (TCGA) to investigate the potential pathways that are differentially expressed between HPV-positive and HPV-negative cancers. mRNA levels were measured by RNA Seq and protein levels by reverse phase protein arrays (RPPA). We also analyzed miRNA levels for both HNSCCs and CESCs, then used TargetScan to identify potential targets for miRNA that were differentially expressed. Results: Proteins involved in extracellular matrix (ECM) adherence including Paxillin and Fibronectin were higher in HPV-negative HNSCCs and CESCs (Paxillin’s p-value= 0.04 for CESCs and p-value Citation Format: Claudia Heymach, Robert Cardnell, Lixia Diao, Jing Wang, Kwok-Shing Ng, Lauren Byers. Proteomic analysis reveals alterations in apoptotic signaling machinery in HPV-associated cancers and identifies BRD4 and BCL2 as potential therapeutic targets in HPV-positive HNSCCs [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B032. doi:10.1158/1535-7163.TARG-19-B032