title: Immunogenicity of the 9-Valent HPV Vaccine Using 2-Dose Regimens in Girls and Boys vs a 3-Dose Regimen in Women.
abstract: Human papillomavirus (HPV) infections cause anogenital cancers and warts. The 9-valent HPV vaccine provides protection against 7 high-risk types of HPV responsible for 90% of cervical cancers and 2 other HPV types accounting for 90% of genital warts.
  
  
  
  To determine whether HPV type-specific antibody responses would be noninferior among girls and boys aged 9 to 14 years after receiving 2 doses of the 9-valent HPV vaccine compared with adolescent girls and young women aged 16 to 26 years receiving 3 doses.
  
  
  
  Open-label, noninferiority, immunogenicity trial conducted at 52 ambulatory care sites in 15 countries. The study was initiated on December 16, 2013, with the last participant visit for this report on June 19, 2015. Five cohorts were enrolled: (1) girls aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (2) boys aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (3) girls and boys aged 9 to 14 years to receive 2 doses 12 months apart (n = 301); (4) girls aged 9 to 14 years to receive 3 doses over 6 months (n = 301); and (5) a control group of adolescent girls and young women aged 16 to 26 years to receive 3 doses over 6 months (n = 314).
  
  
  
  Two doses of the 9-valent HPV vaccine administered 6 or 12 months apart or 3 doses administered over 6 months.
  
  
  
  The primary end point was prespecified as the antibody response against each HPV type assessed 1 month after the last dose using a competitive immunoassay. Each of the three 2-dose regimens was compared with the standard 3-dose schedule in adolescent girls and young women using a noninferiority margin of 0.67 for the ratio of the antibody geometric mean titers.
  
  
  
  Of the 1518 participants (753 girls [mean age, 11.4 years]; 451 boys [mean age, 11.5 years]; and 314 adolescent girls and young women [mean age, 21.0 years]), 1474 completed the study and data from 1377 were analyzed. At 4 weeks after the last dose, HPV antibody responses in girls and boys given 2 doses were noninferior to HPV antibody responses in adolescent girls and young women given 3 doses (P < .001 for each HPV type). Compared with adolescent girls and young women who received 3 doses over 6 months, the 1-sided 97.5% CIs for the ratio of HPV antibody geometric mean titers at 1 month after the last dose across the 9 HPV subtypes ranged from 1.36 to ∞ to 2.50 to ∞ for girls who received 2 doses 6 months apart; from 1.37 to ∞ to 2.55 to ∞ for boys who received 2 doses 6 months apart; and from 1.61 to ∞ to 5.36 to ∞ for girls and boys who received 2 doses 12 months apart.
  
  
  
  Among girls and boys aged 9 to 14 years receiving 2-dose regimens of a 9-valent HPV vaccine separated by 6 or 12 months, immunogenicity 4 weeks after the last dose was noninferior to a 3-dose regimen in a cohort of adolescent girls and young women. Further research is needed to assess persistence of antibody responses and effects on clinical outcomes.
  
  
  
  clinicaltrials.gov Identifier: NCT01984697.
authors.affiliation: Department of Obstetrics and Gynecology, Haukeland University Hospital, University of Bergen, Bergen, Norway.
authors.forename: Ole-Erik
authors.initials: OE
authors.lastname: Iversen
authors.affiliation: Instituto Chileno de Medicina Reproductiva, Santiago, Chile.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Miranda
authors.affiliation: Centre d'Atèncio Primària, EBA Centelles, Barcelona, Spain.
authors.forename: Angels
authors.initials: A
authors.lastname: Ulied
authors.affiliation: Medicus, Clinical Trials, Trondheim, Norway.
authors.forename: Terje
authors.initials: T
authors.lastname: Soerdal
authors.affiliation: Perinatal HIV Research Unit, Baragwanath Hospital, Johannesburg, South Africa.
authors.forename: Erica
authors.initials: E
authors.lastname: Lazarus
authors.affiliation: Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
authors.affiliation: Kentucky Pediatric and Adult Research, Bardstown.
authors.forename: Stan L
authors.initials: SL
authors.lastname: Block
authors.affiliation: G-CENTRUM Olomouc, Olomouc, Czech Republic.
authors.forename: Ales
authors.initials: A
authors.lastname: Skrivanek
authors.affiliation: Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Abdul Ghani
authors.initials: AG
authors.lastname: Nur Azurah
authors.affiliation: Sabah Woman's and Children's Hospital, Hospital Likas, Sabah, Malaysia.
authors.forename: Siew Moy
authors.initials: SM
authors.lastname: Fong
authors.affiliation: Centrum Ambulantní, Brno, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Dvorak
authors.affiliation: Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung-Hyo
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Women's Research Center of Redlands, Terracina Medical Center, Redlands, California.
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Cestero
authors.affiliation: Assaf-Harofeh Medical Center, Zerifin, Israel.
authors.forename: Matitiahu
authors.initials: M
authors.lastname: Berkovitch
authors.affiliation: Hacettepe Üniversitesi Beytepe Kampüsü, Ankara, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Ceyhan
authors.affiliation: Merck & Co Inc, Kenilworth, New Jersey.
authors.forename: Misoo C
authors.initials: MC
authors.lastname: Ellison
authors.affiliation: Merck & Co Inc, Kenilworth, New Jersey.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ritter
authors.affiliation: Merck & Co Inc, Kenilworth, New Jersey.
authors.forename: Shuai S
authors.initials: SS
authors.lastname: Yuan
authors.affiliation: Merck & Co Inc, Kenilworth, New Jersey.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.affiliation: Merck & Co Inc, Kenilworth, New Jersey.
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Saah
authors.affiliation: Merck & Co Inc, Kenilworth, New Jersey.
authors.forename: Alain
authors.initials: A
authors.lastname: Luxembourg
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000918:Antibody Specificity; D002648:Child; D015331:Cohort Studies; D058620:Elder Nutritional Physiological Phenomena; D005260:Female; D005838:Genotype; D006801:Humans; D007115:Immunization Schedule; D000071497:Immunogenicity, Vaccine; D008297:Male; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D012737:Sex Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D053918:Papillomavirus Vaccines