Reassessment of microbial DNA in cancer genomes: addressing contamination controversies

The proposed existence of a widespread "tumor microbiome" has sparked considerable interest, yet recent evidence suggests many microbial DNA signals in cancer genomes arise from contamination rather than true colonization. A September 2025 Science Translational Medicine analysis of over 5700 cancer genomes demonstrated that most detected sequences reflected artifacts, underscoring earlier concerns about low-biomass sequencing studies. While enthusiasm for a universal tumor microbiome must be tempered, robust associations remain in specific cancers, including Helicobacter pylori in gastric carcinoma, Fusobacterium nucleatum in colorectal cancer, and human papillomavirus in cervical malignancies. This reassessment highlights the urgent need for rigorous methodological standards, such as robust negative controls, contamination-aware pipelines, and transparent reporting, to ensure reproducibility. Rather than discouragement, this represents an opportunity to refocus research on biologically plausible, clinically relevant cancer-microbe interactions.