Landscape of oncoviral genotype and co-infection via human papilloma and hepatitis B viral tumor in situ profiling
Adrian Bubie,
Fabien Zoulim,
Barbara Testoni,
Brett Miles,
Marshall Posner,
Augusto Villanueva,
Bojan Losic
Affiliations
Adrian Bubie
Departments of Genetics and Genomic Sciences, New York, NY 10029, USA
Fabien Zoulim
INSERM, U1052, Cancer Research Center of Lyon (CRCL), Lyon, 69008, France
Barbara Testoni
INSERM, U1052, Cancer Research Center of Lyon (CRCL), Lyon, 69008, France
Brett Miles
Department of Otolaryngology Head and Neck Surgery, New York, NY 10029, USA
Marshall Posner
Division of Hematology Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Augusto Villanueva
Departments of Genetics and Genomic Sciences, New York, NY 10029, USA; Division of Liver Diseases, Division of Hematology/Oncology, Department of Medicine, Graduate School of Biomedical Sciences, Tisch Cancer Institute, Diabetes, Obesity, and Metabolism Institute, New York, NY 10029, USA
Bojan Losic
Departments of Genetics and Genomic Sciences, New York, NY 10029, USA; Division of Liver Diseases, Division of Hematology/Oncology, Department of Medicine, Graduate School of Biomedical Sciences, Tisch Cancer Institute, Diabetes, Obesity, and Metabolism Institute, New York, NY 10029, USA; Corresponding author
Summary: The role of oncoviral genotype and co-infection driving oncogenesis remains unclear. We have developed a scalable, high throughput tool for sensitive and precise oncoviral genotype deconvolution. Using tumor RNA sequencing data, we applied it to 537 virally infected liver, cervical, and head and neck tumors, providing the first comprehensive integrative landscape of tumor-viral gene expression, viral antigen immunogenicity, patient survival, and mutational profiling organized by tumor oncoviral genotype. We find that HBV and HPV genotype and co-infection serve as significant predictors of patient survival and immune activation. Finally, we demonstrate that HPV genotype is more associated with viral oncogene expression than cancer type, implying that expression may be similar across episomal and stochastic integration-based infections. While oncoviral infections are known risk factors for oncogenesis, viral genotype and co-infection are shown to strongly associate with disease progression, patient survival, mutational signatures, and putative tumor neoantigen immunogenicity, facilitating novel clinical associations with infections.
