Increased Detection of Merkel Cell Polyomavirus in Non-Melanoma Skin Cancer and Its Association with Host Immunogenetic Profile

Background: Merkel cell polyomavirus (MCPyV) has been established as an etiological agent in Merkel cell carcinoma (MCC), yet its role in other cutaneous neoplasms re-mains under investigation. In the context of non-melanoma skin cancer (NMSC), the influence of host immunogenetics on MCPyV persistence is poorly understood. Objec-tive: To investigate the presence of MCPyV in various skin lesions, particularly NMSC, and its association with cytokine gene polymorphisms related to immune regulation. Methods: We analyzed 274 skin biopsies (lesional, perilesional, and healthy skin) from 84 patients undergoing dermatological evaluation. MCPyV DNA and polymorphisms in IL-6, IL-10, IFN-γ, and TNF-α genes were detected using PCR-based assays. Results: MCPyV was significantly more prevalent in NMSC and non-malignant lesions than in surgical margins or healthy skin (p = 0.050 and 0.048, respectively). Concordance be-tween lesion and margin samples was low (κ = 0.305), suggesting microenviron-ment-specific viral persistence. Notably, high-expression IL-10 genotypes (-1082GG) and low-expression IL-6 genotypes (-174AA) were significantly associated with MCPyV detection (p = 0.048 and p = 0.015, respectively). Conclusion: MCPyV prefer-entially localizes to NMSC lesions, particularly in individuals with immunogenetic profiles favoring viral persistence. Given the unclear role of MCPyV in NMSC patho-genesis, our findings call for comprehensive studies to determine whether the lesional environment facilitates viral persistence or reflects a more complex viral–host interac-tion with potential implications in cutaneous oncogenesis.