Integrative metabolomic and single-cell transcriptomic analysis of recurrent condyloma acuminatum in humans.

Condyloma acuminatum (CA), primarily caused by low-risk HPV6/11, is a benign proliferative disease that is difficult to cure and prone to recurrence. However, the molecular and immune mechanisms underlying relapse remain unclear. We combined metabolomic profiling with single-cell RNA sequencing to investigate recurrence-associated changes. Metabolomics revealed dysregulation of ascorbate and aldarate, glycerophospholipid, purine, and arginine/proline metabolism in recurrent CA. Single-cell analysis identified altered expression of metabolism-related genes (AMD1, GSTM3, ALDH3A1, GPX1, GPX4) in keratinocytes, associated with hyperproliferation, impaired differentiation, and ferroptosis resistance. Immune profiling identified transcriptionally distinct myeloid subpopulations in recurrent CA lesions, including M2 macrophages and dendritic cells. KEGG analysis indicated enrichment of antigen processing, phagosome, and endocytosis pathways in M2 macrophages, and antigen processing and viral carcinogenesis in dendritic cells, suggesting altered immune regulatory states. Notably, the key polyamine biosynthesis regulator AMD1 was downregulated in both M2 macrophages and dendritic cells in recurrent lesions, paralleling metabolic evidence of altered arginine-polyamine pathways. These findings suggest that recurrent CA involves coordinated metabolic dysregulation across keratinocytes and immune cells, highlighting potential targets for immunometabolic intervention.