BACKGROUND: The 9-valent human papillomavirus (HPV) (9vHPV) vaccine targets the four HPV types (6/11/16/18) covered by the licensed quadrivalent HPV (qHPV) vaccine and five additional types (31/33/45/52/58). A large outcome trial of 9vHPV vaccine was conducted. METHODS: An active control (qHPV vaccine) was used because a placebo is not ethically acceptable. Since qHPV vaccine is (and 9vHPV vaccine was anticipated to be) highly efficacious against HPV 6/11/16/18, low incidence of HPV 6/11/16/18-associated disease was expected. Consequently, an efficacy comparison of 9vHPV versus qHPV vaccine for HPV 6/11/16/18 would have been prohibitively large in size. Moreover, no minimum antibody level predicting protection against infection or disease is defined for HPV vaccination. As an alternative approach, the two vaccines were compared using immunogenicity bridging for HPV 6/11/16/18 and clinical efficacy for HPV 31/33/45/52/58. RESULTS: The two co-primary objectives were to demonstrate: (1) non-inferior anti-HPV 6/11/16/18 antibody response; and (2) superior efficacy in HPV 31/33/45/52/58-related clinical outcome, for 9vHPV vaccine versus qHPV vaccine. For HPV 6/11/16/18, supportive analyses included a non-inferiority assessment of the percent risk reduction (compared to historical placebo) for 9vHPV versus qHPV vaccine. CONCLUSIONS: A Phase III study of 9vHPV vaccine was successfully implemented. Experience from this study design may be applicable when developing a multivalent vaccine covering the same serotypes as an existing vaccine plus additional serotypes and there is no immune correlate of protection. Also, this study established that efficacy of a new HPV vaccine may be demonstrated using immunogenicity endpoints, which may open new options in HPV vaccine development.
BACKGROUND: The 9-valent human papillomavirus (HPV) (9vHPV) vaccine targets the four HPV types (6/11/16/18) covered by the licensed quadrivalent HPV (qHPV) vaccine and five additional types (31/33/45/52/58). A large outcome trial of 9vHPV vaccine was conducted. METHODS: An active control (qHPV vaccine) was used because a placebo is not ethically acceptable. Since qHPV vaccine is (and 9vHPV vaccine was anticipated to be) highly efficacious against HPV 6/11/16/18, low incidence of HPV 6/11/16/18-associated disease was expected. Consequently, an efficacy comparison of 9vHPV versus qHPV vaccine for HPV 6/11/16/18 would have been prohibitively large in size. Moreover, no minimum antibody level predicting protection against infection or disease is defined for HPV vaccination. As an alternative approach, the two vaccines were compared using immunogenicity bridging for HPV 6/11/16/18 and clinical efficacy for HPV 31/33/45/52/58. RESULTS: The two co-primary objectives were to demonstrate: (1) non-inferior anti-HPV 6/11/16/18 antibody response; and (2) superior efficacy in HPV 31/33/45/52/58-related clinical outcome, for 9vHPV vaccine versus qHPV vaccine. For HPV 6/11/16/18, supportive analyses included a non-inferiority assessment of the percent risk reduction (compared to historical placebo) for 9vHPV versus qHPV vaccine. CONCLUSIONS: A Phase III study of 9vHPV vaccine was successfully implemented. Experience from this study design may be applicable when developing a multivalent vaccine covering the same serotypes as an existing vaccine plus additional serotypes and there is no immune correlate of protection. Also, this study established that efficacy of a new HPV vaccine may be demonstrated using immunogenicity endpoints, which may open new options in HPV vaccine development.
Authors: Julia M L Brotherton; Mark Jit; Patti E Gravitt; Marc Brisson; Aimée R Kreimer; Sara I Pai; Carole Fakhry; Joseph Monsonego; Silvia Franceschi Journal: Int J Cancer Date: 2016-03-22 Impact factor: 7.396
Authors: Hanna Bergman; Brian S Buckley; Gemma Villanueva; Jennifer Petkovic; Chantelle Garritty; Vittoria Lutje; Alina Ximena Riveros-Balta; Nicola Low; Nicholas Henschke Journal: Cochrane Database Syst Rev Date: 2019-11-22
Authors: Susanne K Kjaer; Mari Nygård; Karin Sundström; Christian Munk; Sophie Berger; Mensur Dzabic; Katrin Elisabeth Fridrich; Marianne Waldstrøm; Sveinung Wergeland Sørbye; Oliver Bautista; Thomas Group; Alain Luxembourg Journal: Hum Vaccin Immunother Date: 2020-12-16 Impact factor: 3.452
Authors: Ángela María Ruiz-Sternberg; Edson D Moreira; Jaime A Restrepo; Eduardo Lazcano-Ponce; Robinson Cabello; Arnaldo Silva; Rosires Andrade; Francisco Revollo; Santos Uscanga; Alejandro Victoria; Ana María Guevara; Joaquín Luna; Manuel Plata; Claudia Nossa Dominguez; Edison Fedrizzi; Eugenio Suarez; Julio C Reina; Misoo C Ellison; Erin Moeller; Michael Ritter; Christine Shields; Miguel Cashat; Gonzalo Perez; Alain Luxembourg Journal: Papillomavirus Res Date: 2017-12-19
Authors: S M Garland; P Pitisuttithum; H Y S Ngan; C-H Cho; C-Y Lee; C-A Chen; Y C Yang; T-Y Chu; N-F Twu; R Samakoses; Y Takeuchi; T H Cheung; S C Kim; L-M Huang; B-G Kim; Y-T Kim; K-H Kim; Y-S Song; S Lalwani; J-H Kang; M Sakamoto; H-S Ryu; N Bhatla; H Yoshikawa; M C Ellison; S R Han; E Moeller; S Murata; M Ritter; M Sawata; C Shields; A Walia; G Perez; A Luxembourg Journal: J Infect Dis Date: 2018-06-05 Impact factor: 5.226
Authors: C Signorelli; A Odone; V Ciorba; P Cella; R A Audisio; A Lombardi; L Mariani; F S Mennini; S Pecorelli; G Rezza; G V Zuccotti; A Peracino Journal: Epidemiol Infect Date: 2017-04-27 Impact factor: 4.434