A 9-Valent HPV Vaccine against Infection and Intraepithelial Neoplasia in Women
N Engl J of Medic 2015 Feb 19 V.372 P.711-723
Elmar A. Joura, M.D., Anna R. Giuliano, Ph.D., Ole-Erik Iversen, M.D., Celine Bouchard, M.D., Constance Mao, M.D., Jesper Mehlsen, M.D., Edson D. Moreira, Jr., M.D., Yuen Ngan, M.D., Lone Kjeld Petersen, M.D., Eduardo Lazcano-Ponce, M.D., Punnee Pitisuttithum, M.D., Jaime Alberto Restrepo, M.D., Gavin Stuart, M.D., Linn Woelber, M.D., Yuh Cheng Yang, M.D., Jack Cuzick, Ph.D., Suzanne M. Garland, M.D., Warner Huh, M.D., Susanne K. Kjaer, M.D., Oliver M. Bautista, Ph.D., Ivan S.F. Chan, Ph.D., Joshua Chen, Ph.D., Richard Gesser, M.D., Erin Moeller, M.P.H., Michael Ritter, B.A., Scott Vuocolo, Ph.D., and Alain Luxembourg, M.D., Ph.D. for the Broad Spectrum HPV Vaccine Study
The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age.
We performed a randomized, international, double-blind, phase 2b–3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV.
The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group.
The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).
N Engl J of Medic 2015 Feb 19 V.372 P.775
From the Centers for Disease Control and Prevention, Atlanta
This issue of the Journal presents a milestone in expanding the coverage of cancers associated with the human papillomavirus (HPV). Joura and colleagues1 report the results of a randomized, controlled trial of a new 9-valent HPV vaccine versus a quadrivalent HPV vaccine in more than 14,000 young women. The authors found that the new vaccine had an efficacy of nearly 97% against high-grade cervical, vulvar, and vaginal disease related to HPV types 31, 33, 45, 52, and 58. In the intention-to-treat analysis, the 9-valent vaccine was not found to be more beneficial than the quadrivalent vaccine, presumably because so many of the study participants, who were between 16 and 26 years of age, had already been infected with the five HPV types added to the new vaccine by the time of the study’s onset. The rationale for vaccination at 11 to 12 years of age is to provide protection before exposure to HPV….