DEK associates with tumor stage and outcome in HPV16 positive oropharyngeal squamous cell carcinoma

// Eric A. Smith 1, * , Bhavna Kumar 2, 3, * , Kakajan Komurov 1 , Stephen M. Smith 4 , Nicole V. Brown 5 , Songzhu Zhao 5 , Pawan Kumar 2, 3 , Theodoros N. Teknos 2, 3 , Susanne I. Wells 1 1 Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA 2 Department of Otolaryngology–Head and Neck Surgery, The Ohio State University, Columbus, OH, 43210, USA 3 The Ohio State University, Comprehensive Cancer Center, Columbus, OH 43210, USA 4 Department of Pathology, The Ohio State University, Columbus, OH, 43210, USA 5 Center for Biostatistics, The Ohio State University, Columbus, OH, 43210, USA * Co-first author Correspondence to: Susanne I. Wells, email: Susanne.Wells@cchmc.org Theodoros N. Teknos, email: ted.teknos@osumc.edu Keywords: DEK, oropharyngeal squamous cell carcinoma, human papillomavirus, IL6, p16 Received: July 18, 2016      Accepted: February 12, 2017      Published: February 21, 2017 ABSTRACT Oropharyngeal squamous cell carcinomas (OPSCC) are common, have poor outcomes, and comprise two biologically and clinically distinct diseases. While OPSCC that arise from human papillomavirus infections (HPV+) have better overall survival than their HPV- counterparts, the incidence of HPV+ OPSCC is increasing dramatically, affecting younger individuals which are often left with life-long co-morbidities from aggressive treatment. To identify patients which do poorly versus those who might benefit from milder regimens, risk-stratifying biomarkers are now needed within this population. One potential marker is the DEK oncoprotein, whose transcriptional upregulation in most malignancies is associated with chemotherapy resistance, advanced tumor stage, and worse outcomes. Herein, a retrospective case study was performed on DEK protein expression in therapy-naive surgical resections from 194 OPSCC patients. We found that DEK was associated with advanced tumor stage, increased hazard of death, and interleukin IL6 expression in HPV16+ disease. Surprisingly, DEK levels in HPV16- OPSCC were not associated with advanced tumor stage or increased hazard of death. Overall, these findings mark HPV16- OPSCC as an exceptional malignancy were DEK expression does not correlate with outcome, and support the potential prognostic utility of DEK to identify aggressive HPV16+ disease.