A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women
Open accessAbstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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).
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HPV vaccines are safe and highly effective against vaccine-type persistent infection and cervical precancerous lesions in women, with vaccine efficacy ≥93%.
“Large international randomised control clinical trials have shown that HPV vaccines are safe and highly effective against vaccine-type persistent infection and cervical precancerous lesions in women (with vaccine efficacy ≥93%).6, 7, 8”
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- Authors
- Joura, E. A., Giuliano, A. R., Iversen, O.-E., Bouchard, C., Mao, C., Mehlsen, J., Moreira, E. D., Ngan, Y., Petersen, L. K., Lazcano-Ponce, E., Pitisuttithum, P., Restrepo, J. A., Stuart, G., Woelber, L., Yang, Y. C., Cuzick, J., Garland, S. M., Huh, W., Kjaer, S. K., Bautista, O. M., Chan, I. S. F., Chen, J., Gesser, R., Moeller, E., Ritter, M., Vuocolo, S., & Luxembourg, A.
- Affiliations
- University of Copenhagen (DK)
- Moffitt Cancer Center (US)
- Haukeland University Hospital (NO)
- University of Washington (US)
- University of Vienna (AT)
- University of Hong Kong (HK)
- Aarhus University Hospital (DK)
- Instituto Nacional de Salud Pública (MX)
- Mahidol University (TH)
- Clínica Medellín SAS (CO)
- University of British Columbia (CA)
- University Medical Center Hamburg-Eppendorf (DE)
- Mackay Memorial Hospital (TW)
- Royal Women's Hospital (AU)
- University of Alabama (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-02-19
- Volume
- 372
- Issue
- 8
- Pages
- 711-723
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1981725818
- Cited by
- 1,433
- References
- 0
- Citations by year
- 2026: 90 · 2025: 115 · 2024: 90 · 2023: 106 · 2022: 101 · 2021: 104 · 2020: 106 · 2019: 121 · 2018: 128 · 2017: 179 · 2016: 169 · 2015: 119 · 2014: 3
- FWCI
- 155.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, other-oa)
- Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
- KUMeL Repository (Keimyung University) (submittedVersion, cc-by-nc-nd)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Funders
- Cancer Research UK (16891)
- Topics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Health Sciences › Medicine › Surgery › Genital Health and Disease
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Keywords
- 9-valent HPV vaccine, human papillomavirus, quadrivalent HPV vaccine, cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, vaccine efficacy, immunogenicity, antibody response, young women
- MeSH terms
- Adolescent, Adult, Antibodies, Viral, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms, Double-Blind Method, Female, Genital Diseases, Female, Humans, Incidence, Papillomavirus Infections, Alphapapillomavirus, Papillomavirus Vaccines, Young Adult, Intention to Treat Analysis
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