Clinical and molecular responses in high-grade intraepithelial neoplasia treated with topical imiquimod 5%

Objective: To assess the clinical and molecular response of patients with r ecurrent high-grade vulvar, vaginal, or cervical intraepithelial neoplasia treated with topical 1-2(2-methylpropyl)-1H-imidazo [4,5-c] quinolin-4-amin e (imiquimod) cream 5%, an immune response modifier wit known efficacy in t he treatment of external genital warts. Methods: This is the first case series in the peer-reviewed literature repo rting the use of imiquimod in high-grade intraepithelial neoplasia of the l ower genital tract. Eight patients with high-grade intraepithelial neoplasi a were treated with imiquimod in the gynecological oncology clinic and the HIV gynecology clinic at The University of Texas Medical Branch at Galvesto n. Frozen biopsies were available for RNA extraction on four patients befor e and after therapy. Using semiquantitative reverse transcription-PCR, we m easured RNA levels of IFNs alpha and gamma, 2',5'-oligoadenylate synthetase , as well as CD4 and CD8 lymphocyte markers. Results: Of the patients treated, four had complete responses, two had part ial responses, one progressed, and one did not tolerate the therapy. Of the four complete responders, two remained disease-free (mean follow-up, 33 mo nths). 2',5'-Oligoadenylate synthetase RNA expression showed an increased t rend after therapy. Conclusions: These results obtained in this small and heterogeneous group m erit further study in the use of topical 5% imiquimod use in the treatment of intraepithelial neoplasia. An important mechanism of action of imiquimod may involve 2',5'-oligoadenylate synthetase antiviral activity.