TY - JOUR
T1 - Long-term immunogenicity, effectiveness, and safety of nine-valent human papillomavirus vaccine in girls and boys 9 to 15 years of age
T2 - Interim analysis after 8 years of follow-up
AU - Olsson, Sven Eric
AU - Restrepo, Jaime Alberto
AU - Reina, Julio Cesar
AU - Pitisuttithum, Punnee
AU - Ulied, Angels
AU - Varman, Meera
AU - Van Damme, Pierre
AU - Moreira, Edson Duarte
AU - Ferris, Daron
AU - Block, Stanley
AU - Bautista, Oliver
AU - Gallagher, Nancy
AU - McCauley, Jennifer
AU - Luxembourg, Alain
N1 - Funding Information:
Medical writing support, under the direction of the authors, was provided by Erin Bekes, PhD, of CMC AFFINITY, McCann Health Medical Communications, and funded by Merck Sharp & Dohme Corp. , a subsidiary of Merck & Co., Inc. , Kenilworth, NJ, USA , in accordance with Good Publication Practice (GPP3) guidelines.
Funding Information:
Pierre Van Damme has received a grant to his institution (University of Antwerp) from Merck & Co., Inc., Kenilworth, NJ, USA for the conduct of this vaccine trial; his institution also received grants from GSK Biologicals, Pfizer, SANOFI, Merck, Takeda, Baxter, CanSino China, Themis, Osivax, J&J, Abbott, The Bill & Melinda Gates Foundation, PATH, Flemish Government, and European Union, outside the submitted work.
Funding Information:
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. The authors and other employees of the sponsor were directly involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and the preparation and review of the manuscript. The opinions expressed in the manuscript represent the collective views of the authors and do not necessarily reflect the official position of the sponsor.The authors would like to thank the study participants and investigators. Medical writing support, under the direction of the authors, was provided by Erin Bekes, PhD, of CMC AFFINITY, McCann Health Medical Communications, and funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA, in accordance with Good Publication Practice (GPP3) guidelines.
Publisher Copyright:
© 2020
PY - 2020/12
Y1 - 2020/12
N2 - Background: The nine-valent human papillomavirus (9vHPV) vaccine protects against infection and disease related to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The pivotal 36-month Phase III immunogenicity study of 9vHPV vaccine in 9- to 15-year-old girls and boys was extended to assess long-term immunogenicity and effectiveness through approximately 10 years after vaccination. We describe results of an interim analysis based on approximately 8 years of follow-up after vaccination. Methods: Participants aged 9–15 years who received three doses of 9vHPV vaccine (at day 1, month 2, and month 6) in the base study and consented to follow-up were enrolled in the long-term follow-up study extension (N = 1272 [females, n = 971; males, n = 301]). Serum was collected at months 66 and 90 to assess antibody responses. For effectiveness analysis, genital swabs were collected (to assess HPV DNA by polymerase chain reaction [PCR]) and external genital examination was conducted (to detect external genital lesions) every 6 months starting when the participant reached 16 years of age. Cervical cytology tests were conducted annually when female participants reached 21 years of age; participants with cytological abnormalities were triaged to colposcopy based on a protocol-specified algorithm. External genital and cervical biopsies of abnormal lesions were performed, and histological diagnoses were adjudicated by a pathology panel. Specimens were tested by PCR to detect HPV DNA. Results: Geometric mean titers for each 9vHPV vaccine HPV type peaked around month 7 and gradually decreased through month 90. Seropositivity rates remained >90% through month 90 for each of the 9vHPV vaccine types by HPV immunoglobulin Luminex Immunoassay. No cases of HPV6/11/16/18/31/33/45/52/58-related high-grade intraepithelial neoplasia or genital warts were observed in the per-protocol population (n = 1107) based on a maximum follow-up of 8.2 years (median 7.6 years) post-Dose 3. Incidence rates of HPV6/11/16/18/31/33/45/52/58-related 6-month persistent infection in females and males were 49.2 and 37.3 per 10,000 person-years, respectively, which were within ranges expected in vaccinated cohorts. There were no vaccine-related SAEs or deaths during the period covered by this interim analysis. Conclusions: The 9vHPV vaccine provided sustained immunogenicity and durable effectiveness through approximately 7 and 8 years, respectively, following vaccination of girls and boys aged 9–15 years.
AB - Background: The nine-valent human papillomavirus (9vHPV) vaccine protects against infection and disease related to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The pivotal 36-month Phase III immunogenicity study of 9vHPV vaccine in 9- to 15-year-old girls and boys was extended to assess long-term immunogenicity and effectiveness through approximately 10 years after vaccination. We describe results of an interim analysis based on approximately 8 years of follow-up after vaccination. Methods: Participants aged 9–15 years who received three doses of 9vHPV vaccine (at day 1, month 2, and month 6) in the base study and consented to follow-up were enrolled in the long-term follow-up study extension (N = 1272 [females, n = 971; males, n = 301]). Serum was collected at months 66 and 90 to assess antibody responses. For effectiveness analysis, genital swabs were collected (to assess HPV DNA by polymerase chain reaction [PCR]) and external genital examination was conducted (to detect external genital lesions) every 6 months starting when the participant reached 16 years of age. Cervical cytology tests were conducted annually when female participants reached 21 years of age; participants with cytological abnormalities were triaged to colposcopy based on a protocol-specified algorithm. External genital and cervical biopsies of abnormal lesions were performed, and histological diagnoses were adjudicated by a pathology panel. Specimens were tested by PCR to detect HPV DNA. Results: Geometric mean titers for each 9vHPV vaccine HPV type peaked around month 7 and gradually decreased through month 90. Seropositivity rates remained >90% through month 90 for each of the 9vHPV vaccine types by HPV immunoglobulin Luminex Immunoassay. No cases of HPV6/11/16/18/31/33/45/52/58-related high-grade intraepithelial neoplasia or genital warts were observed in the per-protocol population (n = 1107) based on a maximum follow-up of 8.2 years (median 7.6 years) post-Dose 3. Incidence rates of HPV6/11/16/18/31/33/45/52/58-related 6-month persistent infection in females and males were 49.2 and 37.3 per 10,000 person-years, respectively, which were within ranges expected in vaccinated cohorts. There were no vaccine-related SAEs or deaths during the period covered by this interim analysis. Conclusions: The 9vHPV vaccine provided sustained immunogenicity and durable effectiveness through approximately 7 and 8 years, respectively, following vaccination of girls and boys aged 9–15 years.
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U2 - 10.1016/j.pvr.2020.100203
DO - 10.1016/j.pvr.2020.100203
M3 - Article
C2 - 32659510
AN - SCOPUS:85088951670
VL - 10
JO - Papillomavirus Research
JF - Papillomavirus Research
SN - 2405-8521
M1 - 100203
ER -