Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts

Randomised controlled trial

Joakim Dillner, Susanne K. Kjaer, Cosette M. Wheeler, Kristján Sigurdsson, Ole Erik Iversen, Mauricio Hernandez-Avila, Gonzalo Perez, Darron R. Brown, Laura A. Koutsky, Eng Hseon Tay, Patricia García, Kevin A. Ault, Suzanne M. Garland, Sepp Leodolter, Sven Eric Olsson, Grace W.K. Tang, Daron Gale Ferris, Jorma Paavonen, Matti Lehtinen, Marc Steben & 16 others F. Xavier Bosch, Elmar A. Joura, Slawomir Majewski, Nubia Muñoz, Evan R. Myers, Luisa L. Villa, Frank J. Taddeo, Christine Roberts, Amha Tadesse, Janine T. Bryan, Roger Maansson, Shuang Lu, Scott Vuocolo, Teresa M. Hesley, Eliav Barr, Richard Haupt

Research output: Contribution to journalArticle

265 Citations (Scopus)

Abstract

Objectives: To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). Design: Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. Setting: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants: 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. Intervention: Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. Main outcome measures: Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. Results: In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. Conclusions: Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. Trial registrations: NCT00092521 and NCT00092534.

Original languageEnglish (US)
Article numberc3493
Number of pages1
JournalBMJ (Online)
Volume341
Issue number7766
DOIs
StatePublished - Jul 31 2010

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Papillomavirus Vaccines
Warts
Randomized Controlled Trials
Vaccines
Neoplasms
Population
Placebos
Human papillomavirus 11
Human papillomavirus 6
Pregnancy Tests
Condylomata Acuminata
Vaginal Smears
Cervical Intraepithelial Neoplasia
Sexual Partners
Primary Health Care
Outcome Assessment (Health Care)
Confidence Intervals
Health

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts : Randomised controlled trial. / Dillner, Joakim; Kjaer, Susanne K.; Wheeler, Cosette M.; Sigurdsson, Kristján; Iversen, Ole Erik; Hernandez-Avila, Mauricio; Perez, Gonzalo; Brown, Darron R.; Koutsky, Laura A.; Tay, Eng Hseon; García, Patricia; Ault, Kevin A.; Garland, Suzanne M.; Leodolter, Sepp; Olsson, Sven Eric; Tang, Grace W.K.; Ferris, Daron Gale; Paavonen, Jorma; Lehtinen, Matti; Steben, Marc; Bosch, F. Xavier; Joura, Elmar A.; Majewski, Slawomir; Muñoz, Nubia; Myers, Evan R.; Villa, Luisa L.; Taddeo, Frank J.; Roberts, Christine; Tadesse, Amha; Bryan, Janine T.; Maansson, Roger; Lu, Shuang; Vuocolo, Scott; Hesley, Teresa M.; Barr, Eliav; Haupt, Richard.

In: BMJ (Online), Vol. 341, No. 7766, c3493, 31.07.2010.

Research output: Contribution to journalArticle

Dillner, J, Kjaer, SK, Wheeler, CM, Sigurdsson, K, Iversen, OE, Hernandez-Avila, M, Perez, G, Brown, DR, Koutsky, LA, Tay, EH, García, P, Ault, KA, Garland, SM, Leodolter, S, Olsson, SE, Tang, GWK, Ferris, DG, Paavonen, J, Lehtinen, M, Steben, M, Bosch, FX, Joura, EA, Majewski, S, Muñoz, N, Myers, ER, Villa, LL, Taddeo, FJ, Roberts, C, Tadesse, A, Bryan, JT, Maansson, R, Lu, S, Vuocolo, S, Hesley, TM, Barr, E & Haupt, R 2010, 'Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: Randomised controlled trial', BMJ (Online), vol. 341, no. 7766, c3493. https://doi.org/10.1136/bmj.c3493
Dillner, Joakim ; Kjaer, Susanne K. ; Wheeler, Cosette M. ; Sigurdsson, Kristján ; Iversen, Ole Erik ; Hernandez-Avila, Mauricio ; Perez, Gonzalo ; Brown, Darron R. ; Koutsky, Laura A. ; Tay, Eng Hseon ; García, Patricia ; Ault, Kevin A. ; Garland, Suzanne M. ; Leodolter, Sepp ; Olsson, Sven Eric ; Tang, Grace W.K. ; Ferris, Daron Gale ; Paavonen, Jorma ; Lehtinen, Matti ; Steben, Marc ; Bosch, F. Xavier ; Joura, Elmar A. ; Majewski, Slawomir ; Muñoz, Nubia ; Myers, Evan R. ; Villa, Luisa L. ; Taddeo, Frank J. ; Roberts, Christine ; Tadesse, Amha ; Bryan, Janine T. ; Maansson, Roger ; Lu, Shuang ; Vuocolo, Scott ; Hesley, Teresa M. ; Barr, Eliav ; Haupt, Richard. / Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts : Randomised controlled trial. In: BMJ (Online). 2010 ; Vol. 341, No. 7766.
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title = "Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: Randomised controlled trial",
abstract = "Objectives: To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). Design: Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. Setting: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants: 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. Intervention: Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. Main outcome measures: Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. Results: In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96{\%} for cervical intraepithelial neoplasia grade I (95{\%} confidence interval 91{\%} to 98{\%}), 100{\%} for both vulvar and vaginal intraepithelial neoplasia grade I (95{\%} CIs 74{\%} to 100{\%}, 64{\%} to 100{\%} respectively), and 99{\%} for condyloma (96{\%} to 100{\%}). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30{\%} (17{\%} to 41{\%}), 75{\%} (22{\%} to 94{\%}), and 48{\%} (10{\%} to 71{\%}) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83{\%} (74{\%} to 89{\%}) for condyloma. Conclusions: Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. Trial registrations: NCT00092521 and NCT00092534.",
author = "Joakim Dillner and Kjaer, {Susanne K.} and Wheeler, {Cosette M.} and Kristj{\'a}n Sigurdsson and Iversen, {Ole Erik} and Mauricio Hernandez-Avila and Gonzalo Perez and Brown, {Darron R.} and Koutsky, {Laura A.} and Tay, {Eng Hseon} and Patricia Garc{\'i}a and Ault, {Kevin A.} and Garland, {Suzanne M.} and Sepp Leodolter and Olsson, {Sven Eric} and Tang, {Grace W.K.} and Ferris, {Daron Gale} and Jorma Paavonen and Matti Lehtinen and Marc Steben and Bosch, {F. Xavier} and Joura, {Elmar A.} and Slawomir Majewski and Nubia Mu{\~n}oz and Myers, {Evan R.} and Villa, {Luisa L.} and Taddeo, {Frank J.} and Christine Roberts and Amha Tadesse and Bryan, {Janine T.} and Roger Maansson and Shuang Lu and Scott Vuocolo and Hesley, {Teresa M.} and Eliav Barr and Richard Haupt",
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TY - JOUR

T1 - Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts

T2 - Randomised controlled trial

AU - Dillner, Joakim

AU - Kjaer, Susanne K.

AU - Wheeler, Cosette M.

AU - Sigurdsson, Kristján

AU - Iversen, Ole Erik

AU - Hernandez-Avila, Mauricio

AU - Perez, Gonzalo

AU - Brown, Darron R.

AU - Koutsky, Laura A.

AU - Tay, Eng Hseon

AU - García, Patricia

AU - Ault, Kevin A.

AU - Garland, Suzanne M.

AU - Leodolter, Sepp

AU - Olsson, Sven Eric

AU - Tang, Grace W.K.

AU - Ferris, Daron Gale

AU - Paavonen, Jorma

AU - Lehtinen, Matti

AU - Steben, Marc

AU - Bosch, F. Xavier

AU - Joura, Elmar A.

AU - Majewski, Slawomir

AU - Muñoz, Nubia

AU - Myers, Evan R.

AU - Villa, Luisa L.

AU - Taddeo, Frank J.

AU - Roberts, Christine

AU - Tadesse, Amha

AU - Bryan, Janine T.

AU - Maansson, Roger

AU - Lu, Shuang

AU - Vuocolo, Scott

AU - Hesley, Teresa M.

AU - Barr, Eliav

AU - Haupt, Richard

PY - 2010/7/31

Y1 - 2010/7/31

N2 - Objectives: To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). Design: Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. Setting: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants: 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. Intervention: Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. Main outcome measures: Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. Results: In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. Conclusions: Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. Trial registrations: NCT00092521 and NCT00092534.

AB - Objectives: To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). Design: Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. Setting: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants: 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. Intervention: Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. Main outcome measures: Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. Results: In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. Conclusions: Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. Trial registrations: NCT00092521 and NCT00092534.

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