title: Prime-boost vaccination strategy in women with high-grade, noncervical anogenital intraepithelial neoplasia: clinical results from a multicenter phase II trial.
abstract: The objective of this study was to determine the clinical effectiveness of a prime-boost human papillomavirus (HPV) vaccine regimen. A nonrandomized phase II prime-boost vaccine trial was conducted. Women with biopsy-proven anogenital intraepithelial neoplasia (AGIN) 3 were vaccinated with three doses of a recombinant fusion protein comprising HPV 16, E6/E7/L2 (TA-CIN) followed by one dose of a recombinant vaccinia virus encoding HPV 16 and 18 E6/E7 (TA-HPV). Clinical responses were evaluated by serial photographs, symptomatology, and biopsies before and after vaccination. Twenty-nine women were vaccinated; 27 with vulval intraepithelial neoplasia 3 and 2 with vaginal intraepithelial neoplasia grade 3. Clinical responses were seen in five women (17%), with one complete and five partial responses. Fifteen women (62%) had symptomatic improvement. No serious adverse effects were recorded. This is the first trial of a prime-boost vaccination regimen using heterologous HPV vaccines (TA-CIN followed by TA-HPV) in the management of AGIN. Since the prime-boost approach in this cohort offered no significant advantages over single TA-HPV vaccination, there are no further studies planned using this protocol. Future studies are warranted to define responders to immunotherapy.
authors.affiliation: Academic Department of Obstetrics and Gynaecology, Wales College of Medicine, Cardiff University, Heath Park, Cardiff, UK. fianderan@cf.ac.uk
authors.forename: A N
authors.initials: AN
authors.lastname: Fiander
authors.forename: A J
authors.initials: AJ
authors.lastname: Tristram
authors.forename: E J
authors.initials: EJ
authors.lastname: Davidson
authors.forename: A E
authors.initials: AE
authors.lastname: Tomlinson
authors.forename: S
authors.initials: S
authors.lastname: Man
authors.forename: P J
authors.initials: PJ
authors.lastname: Baldwin
authors.forename: J C
authors.initials: JC
authors.lastname: Sterling
authors.forename: H C
authors.initials: HC
authors.lastname: Kitchener
mesh_terms: D000328:Adult; D001005:Anus Neoplasms / Q000628:therapy; D002278:Carcinoma in Situ / Q000628:therapy*; D005260:Female; D005833:Genital Neoplasms, Female / Q000628:therapy*; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods*; D008875:Middle Aged; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D014614:Vaccines, Synthetic / Q000627:therapeutic use; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D053918:Papillomavirus Vaccines; D014614:Vaccines, Synthetic; C100344:human papillomavirus vaccine, TA