BACKGROUND: Human papilloma viruses (HPV) are responsible for a variety of proliferative epithelial lesions including anogenital condylomas. These lesions may regress during treatment with an immune-response modifier such as imiquimod. The release of specific cytokines from the monocyte-macrophage lineage 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 examined lesions had been excised in otherwise healthy individuals with a normal immune status. Lesions were examined for the presence of Langerhans cells and subpopulations of the monocyte/macrophage/dendrocyte lineage using immunohistochemical detection of L1-protein, CD68, lysozyme and Factor-XIIIa. CD45R0-positive T lymphocytes were also identified. HPV capsid antigens and genotypes were searched for using immunohistochemistry and in situ hybridization, respectively. RESULTS: The persistent although treated anogenital lesions were identified as 10 viral condylomas, 3 bowenoid papulosis and 1 basal cell carcinoma. The inflammatory cell densities and distributions were similar in the untreated and imiquimod-resistant condylomas with the exception of Factor XIIIa-positive dendrocytes. These dermal dendritic cells were slim and rare in all imiquimod-resistant lesions. In contrast, about two-thirds of the untreated condylomas were enriched in these cells. CONCLUSION: As dermal dendritic cells play a role in the immune surveillance, their low densities in some lesions might be a key feature responsible for low cytokine local production and failure of imiquimod treatment. The combined apparent lack of Langerhans cell activation might suggest that both intraepidermal and intradermal compartments of antigen-presenting cells are affected in imiquimod-resistant lesions.
BACKGROUND:Humanpapilloma viruses (HPV) are responsible for a variety of proliferative epithelial lesions including anogenital condylomas. These lesions may regress during treatment with an immune-response modifier such as imiquimod. The release of specific cytokines from the monocyte-macrophage lineage 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 examined lesions had been excised in otherwise healthy individuals with a normal immune status. Lesions were examined for the presence of Langerhans cells and subpopulations of the monocyte/macrophage/dendrocyte lineage using immunohistochemical detection of L1-protein, CD68, lysozyme and Factor-XIIIa. CD45R0-positive T lymphocytes were also identified. HPV capsid antigens and genotypes were searched for using immunohistochemistry and in situ hybridization, respectively. RESULTS: The persistent although treated anogenital lesions were identified as 10 viral condylomas, 3 bowenoid papulosis and 1 basal cell carcinoma. The inflammatory cell densities and distributions were similar in the untreated and imiquimod-resistant condylomas with the exception of Factor XIIIa-positive dendrocytes. These dermal dendritic cells were slim and rare in all imiquimod-resistant lesions. In contrast, about two-thirds of the untreated condylomas were enriched in these cells. CONCLUSION: As dermal dendritic cells play a role in the immune surveillance, their low densities in some lesions might be a key feature responsible for low cytokine local production and failure of imiquimod treatment. The combined apparent lack of Langerhans cell activation might suggest that both intraepidermal and intradermal compartments of antigen-presenting cells are affected in imiquimod-resistant lesions.
Authors: Michael H Goldschmidt; Jeffrey S Kennedy; Douglas R Kennedy; Hang Yuan; David E Holt; Margret L Casal; Anne M Traas; Elizabeth A Mauldin; Peter F Moore; Paula S Henthorn; Brian J Hartnett; Kenneth I Weinberg; Richard Schlegel; Peter J Felsburg Journal: J Virol Date: 2006-07 Impact factor: 5.103