Dermal dendritic cells in anogenital warty lesions unresponsive to an immune-response modifier

Background: Human papilloma viruses (HPV) are responsible for a variety of proliferative epithelial lesions including anogenital condylomas. These les ions may regress during treatment with an immune-response modifier such as imiquimod. The release of specific cytokines from the monocyte-macrophage l ineage induces a cascade of events abating the HPV replication. Method: A total of 14 persistent warty anogenital lesions were excised 4 to 7 weeks after completing a 4-month imiquimod treatment. Another series of 25 untreated condylomas and 8 bowenoid papulosis served as controls. All ex amined lesions had been excised in otherwise healthy individuals with a nor mal immune status. Lesions were examined for the presence of Langerhans cel ls and subpopulations of the monocyte/macrophage/dendrocyte lineage using i mmunohistochemical detection of L-protein, CD68, lysozyme and Factor-XIIIa. CD45R0-positive T lymphocytes were also identified. HPV capsid antigens an d genotypes were searched for using immunohistochemistry and in situ hybrid ization, respectively. Results: The persistent although treated anogenital lesions were identified as 10 viral condylomas, 3 bowenoid papulosis and 1 basal cell carcinoma. T he inflammatory cell densities and distributions were similar in the untrea ted and imiquimod-resistant condylomas with the exception of Factor-XIIIa-p ositive dendrocytes. These dermal dendritic cells were slim and rare in all imiquimod-resistant lesions. In contrast, about two-thirds of the untreate d condylomas were enriched in these cells. Conclusion: As dermal dendritic cells play a role in the immune surveillanc e, their low densities in some lesions might be a key feature responsible f or low cytokine local production and failure of imiquimod treatment. The co mbined apparent lack of Langerhans cell activation might suggest that both intraepidermal and intradermal compartments of antigen-presenting cells are affected in imiquimod-resistant lesions.