Differences in Imiquimod treatment outcome in two patients with Bowenoid Papulosis containing either episomal or integrated HPV 16.

A61 Bowenoid papulosis (BP) is an intraepithelial neoplasia presenting with multiple, small, well-demarcated papillomatous papules or small patches on the vulva or penile shaft, glans or foreskin. High-risk mucosal HPV types are associated with BP, with HPV 16 most frequently detected. Common treatment modalities of BP include excision, circumcision, electrodessication, laser ablation, cryotherapy, photodynamic therapy, and local administration of 5-fluorouracil. Recurrence rates, however, are high and therefore improvement of therapies is needed. Imiquimod has proven effective in combating viral infections as well as UV-induced (pre) malignant lesions, and seems also effective in the treatment of BP.Because so far imiquimod treatment has not been related to the physical status of HPV, we present here two cases of intraepithelial neoplasia with papillomatous papules or small patches on the penile shaft, glans or foreskin with the clinical diagnosis of BP.For the first patient, histological examination revealed full-thickness epithelial dysplasia, supporting the clinical diagnosis of BP. Because these lesions may be associated with HPV, PCR amplification was performed on extracted DNA from these lesions. Infection with oncogenic HPV has been demonstrated, which turned out to be type 16 after EIA typing. FISH analyses showed diffuse staining of the cell nuclei suggesting the presence of the episomal form of the HPV virus in the lesion. Histology performed 1 month after treatment showed complete absence of epidermal dysplasia. These finding coincided with disappearance of the virus in the lesion, as revealed by PCR and FISH analysis. Nine months after discontinuations treatment no relapse was observed.For the second patient, histological examination of a skin biopsy revealed epithelial hyperplasia and dysplasia. This clinical and histological picture supports the diagnosis of BP. PCR amplification on genomic DNA from this lesion showed also infection with HPV type 16. Interestingly FISH analysis revealed two punctate signals per nucleus.In conclusion, imiquimod treatment provides a promising alternative therapy for BP. Complete cure might be expected when imiquimod treatment is applied to lesions in which HPV is still episomal and not integrated into the cellular genome. The recurrence risk, however, remains to be established and BP patients unresponsive to imiquimod should be evaluated carefully for the development of squamous cell carcinoma.