Distinct Anaerobic Microbial Signature Differentiates Anal Squamous Cell Carcinoma From High-Grade Squamous Intraepithelial Lesions: A Prospective Metagenomic Study

The study examined microbial differences between anal squamous cell carcinoma (ASCC) and high-grade squamous intraepithelial lesions (HSIL) in 121 participants (102 with HSIL and 19 with ASCC). Using metagenomic sequencing, differences in microbial diversity and community composition were identified between groups. ASCC showed lower observed species richness and enrichment of six anaerobic bacteria: Fusobacterium nucleatum, Parvimonas micra, Peptococcus niger, and three Porphyromonas species. All six species remained associated with ASCC during longitudinal follow-up, and five showed greater decline from baseline to month 6 in ASCC compared to HSIL. Twenty-six metabolic pathways were identified linked to these bacteria, involving amino acid metabolism and anaerobic metabolic processes. These findings suggest that a specific microbial signature may be associated with the development of invasive anal cancer.