Hidden within cancer DNA data, researchers uncovered viruses and bacteria that may influence both diagnosis and survival.
Cancer genome sequencing is designed to read human DNA, but it also captures tiny traces of DNA from microbes that ride along in the sample. In a new study from the University of East Anglia (UEA), those microbial traces turned out to be especially revealing in one disease. The researchers report that colorectal cancer stands out from other cancers with a clear microbial “fingerprint,” a pattern distinct enough to separate colorectal tumors from other tumor types.
Colorectal cancer is the fourth most common cancer in the UK and the second deadliest. Because many patients already undergo genetic testing as part of cancer care, the team says this kind of microbial readout could eventually add another layer of insight without requiring an entirely new test.
Their analysis drew on whole genome sequencing (WGS) data from more than 9,000 cancer patients and used Genomics England DNA sequence information from 11,735 cancer samples spanning 22 cancer types. The results also push back on a popular idea in the field, namely that every cancer carries its own unique microbial signature.
“This study changes how we think about the role of microbes in cancer,” said lead researcher Dr. Abraham Gihawi, from UEA’s Norwich Medical School.
How the research happened
Rather than swabbing for pathogens or running a separate infection panel, the approach mines what is already present in sequencing files. That matters because human DNA vastly outweighs microbial DNA in most tumor samples, so teasing out genuine microbial signals requires careful filtering and quality controls to reduce the risk of confusing contamination with biology.
“When you collect cancer DNA sequences, you also gain information from the DNA of microbes contained within the samples,” said Dr. Gihawi.
“We wanted to determine the precise DNA composition of microbes present in each sample. So, we developed computer programs to remove human DNA and analyze the remaining microbe DNA.
“We then correlated this information with clinical data from the patients about their cancer type and clinical outcome.
“What we found challenges previous claims that each cancer type has a distinct microbiological signature or fingerprint.
“But importantly, as whole genome sequencing becomes more common in hospitals, we show that looking at the microbes in tumor samples could become a powerful tool for improving cancer care at little extra cost.”
A breakthrough for colorectal and oral cancers
The colon is one of the most microbe-dense environments in the body, so it is a plausible place for tumor tissue to carry a more consistent microbial pattern than cancers arising in relatively sterile organs. In this dataset, the colorectal signal was not subtle.
“Our results show that only colorectal tumors possess distinctly identifiable microbial communities,” Dr. Gihawi says.
“We found that these microbial signatures were so specific that they could accurately distinguish colorectal tumors from other tumors. We hope that this could help doctors diagnose the disease more precisely and researchers to study the microbes found in colorectal cancer.”
If validated further, that kind of specificity could become useful in tricky diagnostic situations, such as when doctors are trying to determine where a metastatic tumor originally started, or when biopsy samples are small and ambiguous.
The same sequencing-based approach flagged clinically relevant viruses in other cancers, including oral cancers. The study reports accurate detection of HPV (human papillomavirus) compared with current medical tests, which is notable because HPV status can influence how clinicians classify disease and consider treatment options.
The team also detected Human T-Lymphotropic Virus-1 (HTLV-1), a rare virus that can persist silently for years and is linked to certain cancers. Finding such infections incidentally through existing sequencing could be valuable in settings where the virus might otherwise remain undiagnosed.
Better survival rates
Beyond detection, the analysis connected microbial signals to patient outcomes in some sarcoma cases, pointing to a possible future where microbes help refine prognosis or guide treatment strategies.
“We found that certain types of bacteria were associated with poorer survival rates in some cases of sarcoma. This might lead to additional research and treatment options for these types of cancer,” said Dr. Gihawi.
“One of the most exciting things we found was that in some sarcoma cases, the presence of specific bacteria was linked to better survival rates.
“This suggests that microbes might one day help doctors predict how well a patient will respond to treatment and open up new approaches to treatment,” he added.
An indispensable tool
Prof Daniel Brewer, from UEA’s Norwich Medical School, said: “This study highlights the growing clinical value of whole genome sequencing in identifying pathogenic organisms such as HTLV-1 and papillomavirus, which may otherwise go undetected.
“By revealing these hidden infections and providing insight into cancer prognosis – particularly in sarcomas – it demonstrates how genomic analysis is becoming an indispensable tool in precision medicine.
“The findings also suggest that oral cancer, in some cases, may be a close diagnostic consideration, further emphasizing the importance of comprehensive genomic profiling in clinical decision-making.”
Reference: “The landscape of microbial associations in human cancer” by Abraham Gihawi, Henry M. Wood, Jeremy Clark, Justin O’Grady, Rosalind A. Eeles, David C. Wedge, G. Maria Jakobsdottir, Gkikas Magiorkinis, Andrew G. Schache, Liam Masterson, Matt Lechner, Tim R. Fenton, Terry M. Jones, Adrienne M. Flanagan, Solange De Noon, Alex Rubinsteyn, Rachel Hurst, Colin S. Cooper and Daniel S. Brewer, 3 September 2025, Science Translational Medicine.
DOI: 10.1126/scitranslmed.ads6166
This work was funded by the Big C Cancer Charity and Prostate Cancer UK, with further support from The Bob Champion Cancer Trust, The Alan Boswell Group, Masonic Charitable Foundation Successor to the Grand Charity, Movember, Prostate Cancer Research, the King Family, the Hargrave Foundation, NIHR Manchester Biomedical Research Centre and Sarcoma UK.
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