The viral landscape in metastatic solid cancers

Here, we analyze the viral landscape in blood and tissue from 4918 metastatic cancer patients across 38 solid cancer types from the Hartwig Medical Foundation (HMF) cohort, the largest pan-cancer study on metastatic cancer. Using a coverage-based filtering approach, we detected 25 unique viral genera across 32 different cancer types, with a total of 747 unique virus-positive tissue samples. We detected 336 virus-positive blood samples across 29 cancer types, dominated by <i>Torque teno virus</i> and <i>Alphatorquevirus</i>. The tissue samples were dominated by <i>Alphapapillomavirus</i> and <i>Roseolovirus</i>. <i>Alphapapillomavirus</i> was significantly enriched in genital, anal, and colorectal cancers and was associated with host mutational signatures and transcriptional programs related to immunity and DNA repair. Host genes with <i>Alphapapillomavirus</i> integration tended to be more highly expressed and samples with HPV integration had higher somatic mutation rates and higher number of extrachromosomal DNA elements. <i>Alphapapillomavirus</i> was also detected in a significant proportion of blood samples from cervix and anal cancers, suggesting a potential blood-based biomarker.