Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions

a combined analysis of three randomised clinical trials

Elmar A. Joura, Sepp Leodolter, Mauricio Hernandez-Avila, Cosette M. Wheeler, Gonzalo Perez, Laura A. Koutsky, Suzanne M. Garland, Diane M. Harper, Grace WK Tang, Daron Gale Ferris, Marc Steben, Ronald W. Jones, Janine Bryan, Frank J. Taddeo, Oliver M. Bautista, Mark T. Esser, Heather L. Sings, Micki Nelson, John W. Boslego, Carlos Sattler & 2 others Eliav Barr, Jorma Paavonen

Research output: Contribution to journalArticle

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Abstract

Background: Vulval and vaginal cancers among younger women are often related to infection with human papillomavirus (HPV). These cancers are preceded by high-grade vulval intraepithelial neoplasia (VIN2-3) and vaginal intraepithelial neoplasia (VaIN2-3). Our aim was to do a combined analysis of three randomised clinical trials to assess the effect of a prophylactic quadrivalent HPV vaccine on the incidence of these diseases. Methods: 18 174 women (16-26 years) were enrolled and randomised to receive either quadrivalent HPV6/11/16/18 L1 virus-like-particle vaccine or placebo at day 1, and months 2 and 6. Individuals underwent detailed anogenital examination at day 1, 1 month after dose three, and at 6-12-month intervals for up to 48 months. Suspect genital lesions were biopsied and read by a panel of pathologists and vaccine HPV type-specific DNA testing was done. The primary endpoint was the combined incidence of VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. Primary efficacy analyses were done in a per-protocol population. Findings: The mean follow-up time was 3 years. Among women naive to HPV16 or HPV18 through 1 month after dose three (per-protocol population; vaccine n=7811; placebo n=7785), the vaccine was 100% effective (95% CI 72-100) against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. In the intention-to-treat population (which included 18 174 women who, at day 1, could have been infected with HPV16 or HPV18), vaccine efficacy against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18 was 71% (37-88). The vaccine was 49% (18-69) effective against all VIN2-3 or VaIN2-3, irrespective of whether or not HPV DNA was detected in the lesion. The most common treatment-related adverse event was injection-site pain. Interpretation: Prophylactic administration of quadrivalent HPV vaccine was effective in preventing high-grade vulval and vaginal lesions associated with HPV16 or HPV18 infection in women who were naive to these types before vaccination. With time, such vaccination could result in reduced rates of HPV-related vulval and vaginal cancers.

Original languageEnglish (US)
Pages (from-to)1693-1702
Number of pages10
JournalLancet
Volume369
Issue number9574
DOIs
StatePublished - May 19 2007

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Virus-Like Particle Vaccines
Human papillomavirus 11
Human papillomavirus 6
Randomized Controlled Trials
Papillomavirus Vaccines
Vaccines
Vaginal Neoplasms
Vaccination
Placebos
Population
Neoplasms
DNA
Incidence
Infection
Pain
Injections

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions : a combined analysis of three randomised clinical trials. / Joura, Elmar A.; Leodolter, Sepp; Hernandez-Avila, Mauricio; Wheeler, Cosette M.; Perez, Gonzalo; Koutsky, Laura A.; Garland, Suzanne M.; Harper, Diane M.; Tang, Grace WK; Ferris, Daron Gale; Steben, Marc; Jones, Ronald W.; Bryan, Janine; Taddeo, Frank J.; Bautista, Oliver M.; Esser, Mark T.; Sings, Heather L.; Nelson, Micki; Boslego, John W.; Sattler, Carlos; Barr, Eliav; Paavonen, Jorma.

In: Lancet, Vol. 369, No. 9574, 19.05.2007, p. 1693-1702.

Research output: Contribution to journalArticle

Joura, EA, Leodolter, S, Hernandez-Avila, M, Wheeler, CM, Perez, G, Koutsky, LA, Garland, SM, Harper, DM, Tang, GWK, Ferris, DG, Steben, M, Jones, RW, Bryan, J, Taddeo, FJ, Bautista, OM, Esser, MT, Sings, HL, Nelson, M, Boslego, JW, Sattler, C, Barr, E & Paavonen, J 2007, 'Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials', Lancet, vol. 369, no. 9574, pp. 1693-1702. https://doi.org/10.1016/S0140-6736(07)60777-6
Joura, Elmar A. ; Leodolter, Sepp ; Hernandez-Avila, Mauricio ; Wheeler, Cosette M. ; Perez, Gonzalo ; Koutsky, Laura A. ; Garland, Suzanne M. ; Harper, Diane M. ; Tang, Grace WK ; Ferris, Daron Gale ; Steben, Marc ; Jones, Ronald W. ; Bryan, Janine ; Taddeo, Frank J. ; Bautista, Oliver M. ; Esser, Mark T. ; Sings, Heather L. ; Nelson, Micki ; Boslego, John W. ; Sattler, Carlos ; Barr, Eliav ; Paavonen, Jorma. / Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions : a combined analysis of three randomised clinical trials. In: Lancet. 2007 ; Vol. 369, No. 9574. pp. 1693-1702.
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abstract = "Background: Vulval and vaginal cancers among younger women are often related to infection with human papillomavirus (HPV). These cancers are preceded by high-grade vulval intraepithelial neoplasia (VIN2-3) and vaginal intraepithelial neoplasia (VaIN2-3). Our aim was to do a combined analysis of three randomised clinical trials to assess the effect of a prophylactic quadrivalent HPV vaccine on the incidence of these diseases. Methods: 18 174 women (16-26 years) were enrolled and randomised to receive either quadrivalent HPV6/11/16/18 L1 virus-like-particle vaccine or placebo at day 1, and months 2 and 6. Individuals underwent detailed anogenital examination at day 1, 1 month after dose three, and at 6-12-month intervals for up to 48 months. Suspect genital lesions were biopsied and read by a panel of pathologists and vaccine HPV type-specific DNA testing was done. The primary endpoint was the combined incidence of VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. Primary efficacy analyses were done in a per-protocol population. Findings: The mean follow-up time was 3 years. Among women naive to HPV16 or HPV18 through 1 month after dose three (per-protocol population; vaccine n=7811; placebo n=7785), the vaccine was 100{\%} effective (95{\%} CI 72-100) against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. In the intention-to-treat population (which included 18 174 women who, at day 1, could have been infected with HPV16 or HPV18), vaccine efficacy against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18 was 71{\%} (37-88). The vaccine was 49{\%} (18-69) effective against all VIN2-3 or VaIN2-3, irrespective of whether or not HPV DNA was detected in the lesion. The most common treatment-related adverse event was injection-site pain. Interpretation: Prophylactic administration of quadrivalent HPV vaccine was effective in preventing high-grade vulval and vaginal lesions associated with HPV16 or HPV18 infection in women who were naive to these types before vaccination. With time, such vaccination could result in reduced rates of HPV-related vulval and vaginal cancers.",
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T1 - Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions

T2 - a combined analysis of three randomised clinical trials

AU - Joura, Elmar A.

AU - Leodolter, Sepp

AU - Hernandez-Avila, Mauricio

AU - Wheeler, Cosette M.

AU - Perez, Gonzalo

AU - Koutsky, Laura A.

AU - Garland, Suzanne M.

AU - Harper, Diane M.

AU - Tang, Grace WK

AU - Ferris, Daron Gale

AU - Steben, Marc

AU - Jones, Ronald W.

AU - Bryan, Janine

AU - Taddeo, Frank J.

AU - Bautista, Oliver M.

AU - Esser, Mark T.

AU - Sings, Heather L.

AU - Nelson, Micki

AU - Boslego, John W.

AU - Sattler, Carlos

AU - Barr, Eliav

AU - Paavonen, Jorma

PY - 2007/5/19

Y1 - 2007/5/19

N2 - Background: Vulval and vaginal cancers among younger women are often related to infection with human papillomavirus (HPV). These cancers are preceded by high-grade vulval intraepithelial neoplasia (VIN2-3) and vaginal intraepithelial neoplasia (VaIN2-3). Our aim was to do a combined analysis of three randomised clinical trials to assess the effect of a prophylactic quadrivalent HPV vaccine on the incidence of these diseases. Methods: 18 174 women (16-26 years) were enrolled and randomised to receive either quadrivalent HPV6/11/16/18 L1 virus-like-particle vaccine or placebo at day 1, and months 2 and 6. Individuals underwent detailed anogenital examination at day 1, 1 month after dose three, and at 6-12-month intervals for up to 48 months. Suspect genital lesions were biopsied and read by a panel of pathologists and vaccine HPV type-specific DNA testing was done. The primary endpoint was the combined incidence of VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. Primary efficacy analyses were done in a per-protocol population. Findings: The mean follow-up time was 3 years. Among women naive to HPV16 or HPV18 through 1 month after dose three (per-protocol population; vaccine n=7811; placebo n=7785), the vaccine was 100% effective (95% CI 72-100) against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. In the intention-to-treat population (which included 18 174 women who, at day 1, could have been infected with HPV16 or HPV18), vaccine efficacy against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18 was 71% (37-88). The vaccine was 49% (18-69) effective against all VIN2-3 or VaIN2-3, irrespective of whether or not HPV DNA was detected in the lesion. The most common treatment-related adverse event was injection-site pain. Interpretation: Prophylactic administration of quadrivalent HPV vaccine was effective in preventing high-grade vulval and vaginal lesions associated with HPV16 or HPV18 infection in women who were naive to these types before vaccination. With time, such vaccination could result in reduced rates of HPV-related vulval and vaginal cancers.

AB - Background: Vulval and vaginal cancers among younger women are often related to infection with human papillomavirus (HPV). These cancers are preceded by high-grade vulval intraepithelial neoplasia (VIN2-3) and vaginal intraepithelial neoplasia (VaIN2-3). Our aim was to do a combined analysis of three randomised clinical trials to assess the effect of a prophylactic quadrivalent HPV vaccine on the incidence of these diseases. Methods: 18 174 women (16-26 years) were enrolled and randomised to receive either quadrivalent HPV6/11/16/18 L1 virus-like-particle vaccine or placebo at day 1, and months 2 and 6. Individuals underwent detailed anogenital examination at day 1, 1 month after dose three, and at 6-12-month intervals for up to 48 months. Suspect genital lesions were biopsied and read by a panel of pathologists and vaccine HPV type-specific DNA testing was done. The primary endpoint was the combined incidence of VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. Primary efficacy analyses were done in a per-protocol population. Findings: The mean follow-up time was 3 years. Among women naive to HPV16 or HPV18 through 1 month after dose three (per-protocol population; vaccine n=7811; placebo n=7785), the vaccine was 100% effective (95% CI 72-100) against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. In the intention-to-treat population (which included 18 174 women who, at day 1, could have been infected with HPV16 or HPV18), vaccine efficacy against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18 was 71% (37-88). The vaccine was 49% (18-69) effective against all VIN2-3 or VaIN2-3, irrespective of whether or not HPV DNA was detected in the lesion. The most common treatment-related adverse event was injection-site pain. Interpretation: Prophylactic administration of quadrivalent HPV vaccine was effective in preventing high-grade vulval and vaginal lesions associated with HPV16 or HPV18 infection in women who were naive to these types before vaccination. With time, such vaccination could result in reduced rates of HPV-related vulval and vaginal cancers.

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