A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women

Elmar A Joura; Anna R Giuliano; Ole-Erik Iversen; Celine Bouchard; Constance Mao; Jesper Mehlsen; Edson D Moreira; Yuen Ngan; Lone Kjeld Petersen; Eduardo Lazcano-Ponce; Punnee Pitisuttithum; Jaime Alberto Restrepo; Gavin Stuart; Linn Woelber; Yuh Cheng Yang; Jack Cuzick; Suzanne M Garland; Warner Huh; Susanne K Kjaer; Oliver M Bautista; Ivan S F Chan; Joshua Chen; Richard Gesser; Erin Moeller; Michael Ritter; Scott Vuocolo; Alain Luxembourg; Broad Spectrum HPV Vaccine Study

doi:10.1056/nejmoa1405044

A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women

Elmar A Joura, Anna R Giuliano, Ole-Erik Iversen, Celine Bouchard, Constance Mao, Jesper Mehlsen, Edson D Moreira, Yuen Ngan, Lone Kjeld Petersen, Eduardo Lazcano-Ponce, Punnee Pitisuttithum, Jaime Alberto Restrepo, Gavin Stuart, Linn Woelber, Yuh Cheng Yang, Jack Cuzick, Suzanne M Garland, Warner Huh, Susanne K Kjaer, Oliver M BautistaIvan S F Chan, Joshua Chen, Richard Gesser, Erin Moeller, Michael Ritter, Scott Vuocolo, Alain Luxembourg, Broad Spectrum HPV Vaccine Study

Department of Clinical Medicine

759 Citations (Scopus)

Abstract

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).

Original language	English
Journal	New England Journal of Medicine
Volume	372
Issue number	8
Pages (from-to)	711-23
Number of pages	13
ISSN	0028-4793
DOIs	https://doi.org/10.1056/nejmoa1405044
Publication status	Published - 19 Feb 2014

Keywords

Adolescent
Adult
Alphapapillomavirus
Antibodies, Viral
Cervical Intraepithelial Neoplasia
Double-Blind Method
Female
Genital Diseases, Female
Humans
Incidence
Intention to Treat Analysis
Papillomavirus Infections
Papillomavirus Vaccines
Uterine Cervical Neoplasms
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1056/nejmoa1405044

https://www.arca.fiocruz.br/bitstream/icict/13256/2/Joura%20EA%20A%209-valent....pdf

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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., ... Broad Spectrum HPV Vaccine Study (2014). A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. New England Journal of Medicine, 372(8), 711-23. https://doi.org/10.1056/nejmoa1405044

Joura, EA, Giuliano, AR, Iversen, O-E, Bouchard, C, Mao, C, Mehlsen, J, Moreira, ED, Ngan, Y, Petersen, LK, Lazcano-Ponce, E, Pitisuttithum, P, Restrepo, JA, Stuart, G, Woelber, L, Yang, YC, Cuzick, J, Garland, SM, Huh, W, Kjaer, SK, Bautista, OM, Chan, ISF, Chen, J, Gesser, R, Moeller, E, Ritter, M, Vuocolo, S, Luxembourg, A & Broad Spectrum HPV Vaccine Study 2014, 'A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women', New England Journal of Medicine, vol. 372, no. 8, pp. 711-23. https://doi.org/10.1056/nejmoa1405044

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title = "A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women",

abstract = "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).",

keywords = "Adolescent, Adult, Alphapapillomavirus, Antibodies, Viral, Cervical Intraepithelial Neoplasia, Double-Blind Method, Female, Genital Diseases, Female, Humans, Incidence, Intention to Treat Analysis, Papillomavirus Infections, Papillomavirus Vaccines, Uterine Cervical Neoplasms, Young Adult",

author = "Joura, {Elmar A} and Giuliano, {Anna R} and Ole-Erik Iversen and Celine Bouchard and Constance Mao and Jesper Mehlsen and Moreira, {Edson D} and Yuen Ngan and Petersen, {Lone Kjeld} and Eduardo Lazcano-Ponce and Punnee Pitisuttithum and Restrepo, {Jaime Alberto} and Gavin Stuart and Linn Woelber and Yang, {Yuh Cheng} and Jack Cuzick and Garland, {Suzanne M} and Warner Huh and Kjaer, {Susanne K} and Bautista, {Oliver M} and Chan, {Ivan S F} and Joshua Chen and Richard Gesser and Erin Moeller and Michael Ritter and Scott Vuocolo and Alain Luxembourg and {Broad Spectrum HPV Vaccine Study}",

year = "2014",

month = feb,

day = "19",

doi = "10.1056/nejmoa1405044",

language = "English",

volume = "372",

pages = "711--23",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "8",

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TY - JOUR

T1 - A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women

AU - Joura, Elmar A

AU - Giuliano, Anna R

AU - Iversen, Ole-Erik

AU - Bouchard, Celine

AU - Mao, Constance

AU - Mehlsen, Jesper

AU - Moreira, Edson D

AU - Ngan, Yuen

AU - Petersen, Lone Kjeld

AU - Lazcano-Ponce, Eduardo

AU - Pitisuttithum, Punnee

AU - Restrepo, Jaime Alberto

AU - Stuart, Gavin

AU - Woelber, Linn

AU - Yang, Yuh Cheng

AU - Cuzick, Jack

AU - Garland, Suzanne M

AU - Huh, Warner

AU - Kjaer, Susanne K

AU - Bautista, Oliver M

AU - Chan, Ivan S F

AU - Chen, Joshua

AU - Gesser, Richard

AU - Moeller, Erin

AU - Ritter, Michael

AU - Vuocolo, Scott

AU - Luxembourg, Alain

AU - Broad Spectrum HPV Vaccine Study

PY - 2014/2/19

Y1 - 2014/2/19

N2 - 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).

AB - 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).

KW - Adolescent

KW - Adult

KW - Alphapapillomavirus

KW - Antibodies, Viral

KW - Cervical Intraepithelial Neoplasia

KW - Double-Blind Method

KW - Female

KW - Genital Diseases, Female

KW - Humans

KW - Incidence

KW - Intention to Treat Analysis

KW - Papillomavirus Infections

KW - Papillomavirus Vaccines

KW - Uterine Cervical Neoplasms

KW - Young Adult

U2 - 10.1056/nejmoa1405044

DO - 10.1056/nejmoa1405044

M3 - Journal article

C2 - 25693011

SN - 0028-4793

VL - 372

SP - 711

EP - 723

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 8

ER -

A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women

Abstract

Keywords

UN SDGs

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