title: Clinical and molecular responses in high-grade intraepithelial neoplasia treated with topical imiquimod 5%.
abstract: OBJECTIVE
  To assess the clinical and molecular response of patients with recurrent high-grade vulvar, vaginal, or cervical intraepithelial neoplasia treated with topical 1-2(2-methylpropyl)-1H-imidazo [4,5-c] quinolin-4-amine (imiquimod) cream 5%, an immune response modifier with known efficacy in the treatment of external genital warts.
  
  
  METHODS
  This is the first case series in the peer-reviewed literature reporting the use of imiquimod in high-grade intraepithelial neoplasia of the lower genital tract. Eight patients with high-grade intraepithelial neoplasia were treated with imiquimod in the gynecological oncology clinic and the HIV gynecology clinic at The University of Texas Medical Branch at Galveston. Frozen biopsies were available for RNA extraction on four patients before and after therapy. Using semiquantitative reverse transcription-PCR, we measured 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 partial responses, one progressed, and one did not tolerate the therapy. Of the four complete responders, two remained disease-free (mean follow-up, 33 months). 2',5'-Oligoadenylate synthetase RNA expression showed an increased trend after therapy.
  
  
  CONCLUSIONS
  These results obtained in this small and heterogeneous group merit 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.
authors.affiliation: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0587, USA. carrasti@utmb.edu
authors.forename: C
authors.initials: C
authors.lastname: Diaz-Arrastia
authors.forename: I
authors.initials: I
authors.lastname: Arany
authors.forename: S C
authors.initials: SC
authors.lastname: Robazetti
authors.forename: T V
authors.initials: TV
authors.lastname: Dinh
authors.forename: Z
authors.initials: Z
authors.lastname: Gatalica
authors.forename: S K
authors.initials: SK
authors.lastname: Tyring
authors.forename: E
authors.initials: E
authors.lastname: Hannigan
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000287:Administration, Topical; D000328:Adult; D000634:Aminoquinolines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D000077271:Imiquimod; D008875:Middle Aged; D009824:Ointments; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics; D014625:Vaginal Neoplasms / Q000188:drug therapy / Q000235:genetics; D014846:Vulvar Neoplasms / Q000188:drug therapy / Q000235:genetics; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy* / Q000235:genetics
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D009824:Ointments; D012334:RNA, Neoplasm; D015088:2',5'-Oligoadenylate Synthetase; D000077271:Imiquimod