Several studies have reported resident microbes in tumors that may shape tumor biology. But a new study suggests that many of these reported microbial signals may be contamination. 

The findings, published in Cell, suggest that tumor microbiotas appear mainly in cancers of the mouth and digestive tract, and their makeup is linked to the number of DNA mutations in a tumor’s cells.

Some microbes have been linked to specific cancers, such as HPV in cervical and oral cancers, Epstein-Barr virus in some gastric and nasopharyngeal cancers, Helicobacter pylori in stomach cancer, and several bacteria in colorectal cancer. But past studies have disagreed about whether other tumor types also contain resident microbes. 

Anders Dohlman at Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues built a pipeline to detect microbial DNA in tumor genome sequencing data while removing human DNA and other contamination.

Rigorous pipeline

The pipeline removes human DNA as thoroughly as possible, identifies any remaining microbial DNA, and estimates how much microbial material is present. 

The researchers tested the pipeline on mixtures of human and microbial DNA and found that it detected microbial DNA even when it was present at extremely low levels.

Then, the team applied the pipeline to more than 16,000 tumor genomes. As expected, colorectal tumors had stronger microbial signals than blood and brain tumors. But blood and brain samples still showed some microbes that looked like environmental or lab contaminants, the researchers found.

Microbial colonization 

Most cancer types did not contain convincing tumor microbiotas, except for cancers of the mouth, throat, esophagus, stomach, and colon-rectum. These tumors often hosted diverse microbes, including bacteria, fungi, viruses, and archaea. 

Tumor mutation burden—the number of DNA mutations in a tumor’s cells—was a stronger predictor of microbial levels than tumor subtype. Tumors with more mutations tended to contain more microbial DNA, likely because their altered immune environments make them easier for microbes to colonize, the researchers say.

Although some microbes may have been missed or misclassified, the authors add, “our analysis helps resolve persistent uncertainty stemming from conflicting reports about the scope and distribution of microbial colonization across cancer sites.”