Genoprevalence of cutavirus in benign and malignant intestinal and breast tissues

Cutavirus (CuV), the newest human protoparvovirus (PPV), has gained attention due to its significant association with cutaneous T-cell lymphoma (CTCL) and its precursor, parapsoriasis, whereas the other human PPVs, bufavirus and tusavirus, show no such link. Given this association, it is important to investigate the prevalence of CuV DNA in other tissues, particularly those affected by malignancy or inflammation. This study assessed, by multiplex quantitative PCR, the genoprevalences of all three PPVs in 427 fresh-frozen intestinal biopsies from inflammatory bowel disease (IBD), colorectal cancer, adenomas or healthy mucosa of 185 individuals, as well as in 94 formalin-fixed paraffin-embedded (FFPE) biopsies from malignant and non-malignant breast conditions of 85 patients. The study also compared the DNA prevalences of human herpesvirus (HHV)-6A, -6B and -7 in the breast tissues. CuV mRNA was assayed with reverse-transcription PCR, and corresponding FFPE sections underwent in situ hybridization. CuV DNA was detected in intestinal IBD or healthy mucosa from 6/185 (3.2%) subjects, but no CuV mRNA or in situ signals were detected. In breast biopsies, HHV-6B and HHV-7 DNAs were present in 20.3 and 5.1%, respectively, while all PPVs and HHV-6A were absent. Overall, CuV was absent in all 70 cancer tissues, underscoring its association with CTCL. The low CuV DNA loads and prevalences in intestinal and breast morbidities, and lack of activity, suggest that CuV is unlikely to play a role in these malignancies or inflammatory conditions. In contrast, HHV-6B may be more relevant to breast pathology, even though it is also widely detected in healthy tissues. Nevertheless, our study provides insight into persistent DNA viruses implicated in cancer and highlights their occurrence across various disease manifestations, laying a foundation for future studies.