title: Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6 L2E7 vaccine: infection of external anogenital warts with multiple HPV types and failure of therapeutic vaccination.
abstract: BACKGROUND
  Cellular immunity is involved in spontaneous clearance of anogenital warts caused, most typically, by human papillomavirus (HPV) type 6 or 11, supporting the concept of therapeutic vaccination. A therapeutic vaccine composed of HPV-6 L2E7 fusion protein and AS02A adjuvant was evaluated in conjunction with conventional therapies in subjects with anogenital warts.
  
  
  METHODS
  A total of 457 subjects with anogenital warts were screened, of which 320 with HPV-6 and/or HPV-11 infection were enrolled into 2 double-blind, placebo-controlled substudies. Three doses of vaccine or placebo were administered along with either ablative therapy or podophyllotoxin.
  
  
  RESULTS
  Although a positive trend toward clearance was seen in patients infected with only HPV-6, in neither substudy did the vaccine significantly increase the efficacy of conventional therapies, despite induction of adequate immune responses. Extensive HPV typing by polymerase chain reaction demonstrated that a majority of screened subjects (73.7%) were infected with HPV-6 and/or HPV-11 and that a large proportion (40.1%) were infected with multiple HPV types. HPV types that put subjects at high risk of development of cervical cancer were detected in 39.8% of subjects.
  
  
  CONCLUSIONS
  Infection with multiple HPV types, including high-risk types, is common in anogenital wart disease. Therapeutic vaccination failed to increase the efficacy of conventional therapies.
authors.affiliation: GlaxoSmithKline Biologicals, Rixensart, Belgium. pierre.vandepapeliere@gskbio.com
authors.forename: Pierre
authors.initials: P
authors.lastname: Vandepapeliere
authors.forename: Renzo
authors.initials: R
authors.lastname: Barrasso
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Jan M M
authors.initials: JM
authors.lastname: Walboomers
authors.forename: Martine
authors.initials: M
authors.lastname: Wettendorff
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Stanberry
authors.forename: Charles J N
authors.initials: CJ
authors.lastname: Lacey
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D003218:Condylomata Acuminata / Q000276:immunology / Q000628:therapy* / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005838:Genotype; D052163:Human papillomavirus 6 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D027383:Papillomaviridae / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D053918:Papillomavirus Vaccines; D010919:Placebos; D011034:Podophyllotoxin / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use*; D014765:Viral Vaccines / Q000627:therapeutic use*
chemical_list: C501939:ASO2A adjuvant; D000276:Adjuvants, Immunologic; D036022:Capsid Proteins; D004279:DNA, Viral; D004338:Drug Combinations; C082746:L2 oncogene viral capsid protein, Human papillomavirus type 6; D008050:Lipid A; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D010919:Placebos; D012503:Saponins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C062495:oncogene protein E7, Human papillomavirus type 6; D011034:Podophyllotoxin