Virostatische und immunmodulatorische Lokaltherapie bei rezidivierenden HPV-assoziierten hochgradigen vulvären intraepithelialen Neoplasien: Eine Pilotstudie

Abstract

OBJECTIVES: Aim of the study was to test the efficacy of a local virostatic and immunomodulatory therapy for recurrent HPV-associated vulvar intraepithelial neoplasias (VIN) and to evaluate the effect of imiquimod on dendritic cells. METHODS: Three women with recurrent VIN treated previously with surgical excision and laser destruction developed new VIN lesions. They received local treatment with 5 % imiquimod cream for 2 weeks alternating with 1 % cidofovir gel for 2 weeks for a total period of 12 weeks. Expression surface markers on antigen-presenting dendritic cells after treatment with imiquimod were analyzed. RESULTS: All biopsies revealed HPV 16 DNA. At 1 and 5 months after completion of local therapy, all 3 patients had clinical and histological remission without detectable HPV 16 DNA. One patient was disease-free for 5 years before developing a recurrent VIN lesion again. She was treated locally with imiquimod and cidovir for a second time, which resulted in complete remission. Both other patients remained free of recurrence during the whole period. After incubation with imiquimod, dendritic cells revealed an increased expression of surface markers CD80/B7.1, CD 86/B7.2 and CD40, CD54/ICAM-1 and CD83. CONCLUSION: Virostatic and immunomodulatory local therapy is an effective noninvasive treatment alternative for recurrent HPV-associated high grade VIN. The effect of imiquimod might be based on an enhanced presentation of HPV-antigens to lymphocytes with subsequent destruction. This might be the result of an increased expression of co-stimulatory molecules and surface markers on the cell membrane of antigen presenting dendritic cells.