Eleven pathogens have been classified as carcinogenic agents in humans by the International Agency for Research on Cancer (IARC) 3. Cancers that are attributable to infections have a greater incidence than any individual type of cancer worldwide. The World Health Organization estimates that 15.4% of all cancers are attributable to infections and 9.9% are linked to viruses 1, 2. High levels of endogenous retrovirus (ERV1) expression were linked to a worse survival outcome in patients with kidney cancer. Integrations at the TERT promoter were associated with high telomerase expression evidently activating this tumor-driving process. For HBV, HPV16, HPV18 and adeno-associated virus-2 (AAV2), viral integration was associated with local variations in genomic copy numbers. The study revealed significant exclusivity of HPV and driver mutations in head-and-neck cancer and the association of HPV with APOBEC mutational signatures, which suggests that impaired antiviral defense is a driving force in cervical, bladder and head-and-neck carcinoma. We found a high prevalence of known tumor-associated viruses such as Epstein–Barr virus (EBV), hepatitis B virus (HBV) and human papilloma virus (HPV for example, HPV16 or HPV18).
Viruses were detected in 382 genome and 68 transcriptome datasets. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, for which whole-genome and-for a subset-whole-transcriptome sequencing data from 2,658 cancers across 38 tumor types was aggregated, we systematically investigated potential viral pathogens using a consensus approach that integrated three independent pipelines.
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