The virome of HPV-positive tonsil squamous cell carcinoma and neck metastasis

// Ryan M. Carey 1 , * , Karthik Rajasekaran 1 , * , Tyler Seckar 1 , Xiang Lin 2 , Zhi Wei 2 , Charles C.L. Tong 1 , Viran J. Ranasinghe 1 , Jason G. Newman 1 , Bert W. O'Malley Jr. 1 , Gregory S. Weinstein 1 , Michael D. Feldman 3 and Erle S. Robertson 1 1 Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA 2 Department of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA 3 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA * Co-first authors Correspondence to: Erle S. Robertson, email: erle@pennmedicine.upenn.edu Keywords: HPV; cancer; virus; virome; oropharyngeal squamous cell carcinoma Received: November 06, 2019     Accepted: December 29, 2019     Published: January 21, 2020 ABSTRACT Oropharyngeal squamous cell carcinoma (OPSCC) represents the most common HPV-related malignancy in the United States with increasing incidence. There is heterogeneity between the behavior and response to treatment of HPV-positive oropharyngeal squamous cell carcinoma that may be linked to the tumor virome. In this prospective study, a pan-pathogen microarray (PathoChip) was used to determine the virome of early stage, p16-positive OPSCC and neck metastasis treated with transoral robotic surgery (TORS) and neck dissection. The virome findings of primary tumors and neck lymph nodes were correlated with clinical data to determine if specific organisms were associated with clinical outcomes. A total of 114 patients were enrolled in the study. Double-stranded DNA viruses, specifically Papillomaviridae, showed the highest hybridization signal (viral copies) across all viral families in the primary and positive lymph node samples. High hybridization signals were also detected for signatures of Baculoviridae, Reoviridae, Siphoviridae, Myoviridae, and Polydnaviridae in most of the cancer specimens, including the lymph nodes without cancer present. Across all HPV signatures, HPV16 and 18 had the highest average hybridization signal index and prevalence. To our knowledge, this is the first study that has identified the viral signatures of OPSCC tumors. This will serve as a foundation for future research investigating the role of the virome in OPSCC. Further investigation into the OPSCC microbiome and its variations may allow for improved appreciation of the impact of microbial dysbiosis on risk stratification, oncologic outcomes, and treatment response which has been shown in other cancer sites.