title: Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls.
abstract: BACKGROUND
  To evaluate co-administration of GlaxoSmithKline Biologicals' human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB).
  
  
  METHODS
  This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV (n=247), HepB (n=247) or HPV co-administered with HepB (HPV+HepB; n=247) at Months 0, 1 and 6. Antibodies against hepatitis B surface antigen (HBs), HPV-16 and HPV-18 were measured, and reactogenicity and safety monitored. Co-primary objectives were to demonstrate non-inferiority of hepatitis B and HPV-16/18 immune responses at Month 7 for co-administered vaccines, compared with vaccines administered alone, in the according-to-protocol cohort.
  
  
  RESULTS
  The pre-defined criteria for non-inferiority were met for all co-primary immunogenicity endpoints at Month 7. Anti-HBs seroprotection rates ≥10mIU/mL were achieved by 97.9% and 100% of girls, respectively, following co-administration or HepB alone. Anti-HBs geometric mean titers (GMTs) (95% confidence interval) were 1280.9 (973.3-1685.7) and 3107.7 (2473.1-3905.1) milli-international units/mL, respectively. Anti-HPV-16 and -18 seroconversion rates were achieved by ≥99% of girls following co-administration or HPV alone. Anti-HPV-16 GMTs were 19819.8 (16856.9-23303.6) and 21712.6 (19460.2-24225.6) ELISA units (ELU)/mL, respectively. Anti-HPV-18 GMTs were 8835.1 (7636.3-10222.1) and 8838.6 (7948.5-9828.4) ELU/mL, respectively. Co-administration was generally well tolerated.
  
  
  CONCLUSIONS
  The study results support the co-administration of HPV-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine in adolescent girls aged 9-15 years.
  
  
  BACKGROUND
  ClinicalTrials.gov registration number NCT00652938.
authors.affiliation: Department of Obstetrics/Gynecology 791, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, Netherlands. C.Schmeink@obgyn.umcn.nl
authors.forename: Channa E
authors.initials: CE
authors.lastname: Schmeink
authors.forename: Ruud L M
authors.initials: RL
authors.lastname: Bekkers
authors.forename: Ann
authors.initials: A
authors.lastname: Josefsson
authors.forename: Jan H
authors.initials: JH
authors.lastname: Richardus
authors.forename: Katarina
authors.initials: K
authors.lastname: Berndtsson Blom
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: David
authors.forename: Kurt
authors.initials: K
authors.lastname: Dobbelaere
authors.forename: Dominique
authors.initials: D
authors.lastname: Descamps
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D002648:Child; D005260:Female; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D009426:Netherlands; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D013548:Sweden
chemical_list: D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D053918:Papillomavirus Vaccines