The landscape of microbial associations in human cancer

Gihawi, Abraham, Wood, Henry M., Clark, Jeremy, O'Grady, Justin, Eeles, Rosalind A., Wedge, David C., Jakobsdottir, G. Maria, Magiorkinis, Gkikas, Schache, Andrew G., Masterson, Liam, Lechner, Matt, Fenton, Tim R., Jones, Terry M., Flanagan, Adrienne M., De Noon, Solange, Rubinsteyn, Alex, Hurst, Rachel, Cooper, Colin S. and Brewer, Daniel S. (2025) The landscape of microbial associations in human cancer. Science Translational Medicine, 17 (814). ISSN 1946-6234

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Abstract

Oncomicrobes are estimated to cause 15% of cancers worldwide. When cancer whole-genome sequencing (WGS) data are collected, the microbes present are also sequenced, allowing the investigation of potential etiological and clinical associations. Interrogating the microbial community for 8908 patients encompassing 22 cancer types from the Genomics England WGS dataset revealed that only colorectal tumors exhibited unmistakably distinct microbial communities that can reliably be used to distinguish anatomical site [positive predictive value (PPV) = 0.95]. This pattern was validated in two independent datasets. Potential clinical relevance uncovered by our analyses included accurate detection of alphapapillomaviruses [human papillomavirus (HPV)] in oral cancers, when compared with current clinical standards, and the detection of rare, highly pathogenic viruses such as human T-lymphotropic virus–1. Biomarker investigations demonstrated statistically significant associations (P < 0.05) between a subset of anaerobic bacteria and survival in certain subtypes of sarcoma. Our results contradict previous claims that each cancer type has a distinct microbiological signature but highlight the potential value of microbial analysis for certain cancers as WGS of tumor samples becomes common in the clinic.

Item Type:	Article
Additional Information:	Data and materials availability: All data associated with this study are present in the paper or the Supplementary Materials. The Kraken database consists of GRCh38 and all bacterial, viral (which includes bacteriophages), fungal, and protozoal genomes at the scaffold level and above (constituent genomes can be found at https://doi.org/10.5281/zenodo.15739381). Community matrices, analysis scripts, and DNA reads unmapped to the human genome are available within the Genomics England research environment for researchers to access. The community matrix used is located at the file path: /re_gecip/shared_all_GeCIPs/Abe/all_kraken_community.tsv. Funding: This work was funded by the Big C Cancer Charity (ref 16-09R, recipient: D.S.B.) and Prostate Cancer UK (research grant ref. MA-ETNA19-003, recipient: D.S.B.; RIA15-ST2-029, recipients: D.S.B. and C.S.C.; and TLD-CAF22-011, recipient: A.G.). We are grateful for and acknowledge support from the Masonic Charitable Foundation Successor to the Grand Charity (recipient: C.S.C.), Movember (C.S.C.), Prostate Cancer Research (D.S.B.), the King Family (C.S.C), and the Stephen Hargrave Trust (recipient: C.S.C.). D.C.W. and G.M.J. were supported by the NIHR Manchester Biomedical Research Centre (NIHR203308). A.M.F. is supported by Sarcoma UK (SUKG01.2018).
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Depositing User:	LivePure Connector
Date Deposited:	08 Sep 2025 10:30
Last Modified:	11 Sep 2025 23:58
URI:	https://ueaeprints.uea.ac.uk/id/eprint/100295
DOI:	10.1126/scitranslmed.ads6166

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