Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women.
A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine.
Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16-26 years, and an immunogenicity and safety study in girls and boys aged 9-15 years. Participants (N=5312) received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs) were also monitored in all participants.
The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6). Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99%) 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity.
The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden.
Ruiz-Sternberg ÁM
，Moreira ED Jr
，Restrepo JA
，Lazcano-Ponce E
，Cabello R
，Silva A
，Andrade R
，Revollo F
，Uscanga S
，Victoria A
，Guevara AM
，Luna J
，Plata M
，Dominguez CN
，Fedrizzi E
，Suarez E
，Reina JC
，Ellison MC
，Moeller E
，Ritter M
，Shields C
，Cashat M
，Perez G
，Luxembourg A
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Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial.
Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years.
We undertook this randomised, double-blind, efficacy, immunogenicity, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16-26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central randomisation and block sizes of 2 and 2 to receive three intramuscular injections over 6 months of 9vHPV or qHPV (control) vaccine. All participants, study investigators, and study site personnel, laboratory staff, members of the sponsor's study team, and members of the adjudication pathology panel were masked to vaccination groups. The primary outcomes were incidence of high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, invasive cervical carcinoma), vulvar disease (vulvar intraepithelial neoplasia grade 2/3, vulvar cancer), and vaginal disease (vaginal intraepithelial neoplasia grade 2/3, vaginal cancer) related to HPV 31, 33, 45, 52, and 58 and non-inferiority (excluding a decrease of 1·5 times) of anti-HPV 6, 11, 16, and 18 geometric mean titres (GMT). Tissue samples were adjudicated for histopathology diagnosis and tested for HPV DNA. Serum antibody responses were assessed by competitive Luminex immunoassay. The primary evaluation of efficacy was a superiority analysis in the per-protocol efficacy population, supportive efficacy was analysed in the modified intention-to-treat population, and the primary evaluation of immunogenicity was a non-inferiority analysis. The trial is registered with ClinicalTrials.gov, number NCT00543543.
Between Sept 26, 2007, and Dec 18, 2009, we recruited and randomly assigned 14 215 participants to receive 9vHPV (n=7106) or qHPV (n=7109) vaccine. In the per-protocol population, the incidence of high-grade cervical, vulvar and vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0·5 cases per 10 000 person-years in the 9vHPV and 19·0 cases per 10 000 person-years in the qHPV groups, representing 97·4% efficacy (95% CI 85·0-99·9). HPV 6, 11, 16, and 18 GMTs were non-inferior in the 9vHPV versus qHPV group from month 1 to 3 years after vaccination. No clinically meaningful differences in serious adverse events were noted between the study groups. 11 participants died during the study follow-up period (six in the 9vHPV vaccine group and five in the qHPV vaccine group); none of the deaths were considered vaccine-related.
The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58. Both the 9vHPV vaccine and qHPV vaccine had a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18. Vaccine efficacy was sustained for up to 6 years. The 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide.
Merck & Co, Inc.
Huh WK
，Joura EA
，Giuliano AR
，Iversen OE
，de Andrade RP
，Ault KA
，Bartholomew D
，Cestero RM
，Fedrizzi EN
，Hirschberg AL
，Mayrand MH
，Ruiz-Sternberg AM
，Stapleton JT
，Wiley DJ
，Ferenczy A
，Kurman R
，Ronnett BM
，Stoler MH
，Cuzick J
，Garland SM
，Kjaer SK
，Bautista OM
，Haupt R
，Moeller E
，Ritter M
，Roberts CC
，Shields C
，Luxembourg A
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