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 G Ferris; Jorma Paavonen; Matti Lehtinen; Marc Steben; 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; FUTURE I/II Study Group

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 G Ferris, Jorma Paavonen, Matti Lehtinen, Marc StebenF 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, FUTURE I/II Study Group

Department of Clinical Medicine

288 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 language	English
Journal	BMJ - British Medical Journal - Clinical Research Edition
Volume	341
Pages (from-to)	c3493
ISSN	0959-8138
Publication status	Published - 31 Jul 2010

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Dillner, J., Kjaer, S. K., Wheeler, C. M., Sigurdsson, K., Iversen, O-E., Hernandez-Avila, M., Perez, G., Brown, D. R., Koutsky, L. A., Tay, E. H., García, P., Ault, K. A., Garland, S. M., Leodolter, S., Olsson, S-E., Tang, G. W. K., Ferris, D. G., Paavonen, J., Lehtinen, M., ... FUTURE I/II Study Group (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 - British Medical Journal - Clinical Research Edition, 341, c3493.

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 et al.

In: BMJ - British Medical Journal - Clinical Research Edition, Vol. 341, 31.07.2010, p. c3493.

Research output: Contribution to journal › Journal article › Research › peer-review

Dillner, J, Kjaer, SK, Wheeler, CM, Sigurdsson, K, Iversen, O-E, Hernandez-Avila, M, Perez, G, Brown, DR, Koutsky, LA, Tay, EH, García, P, Ault, KA, Garland, SM, Leodolter, S, Olsson, S-E, 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 & FUTURE I/II Study Group 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 - British Medical Journal - Clinical Research Edition, vol. 341, pp. c3493.

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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 Ole-Erik Iversen 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 Sven-Eric Olsson and Tang, {Grace W K} and Ferris, {Daron G} 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 and Brown, {Peter De Nully}",

year = "2010",

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day = "31",

language = "English",

volume = "341",

pages = "c3493",

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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: 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 G

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

AU - FUTURE I/II Study Group

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.

M3 - Journal article

SN - 0959-8138

VL - 341

SP - c3493

JO - B M J (Clinical Research Edition)

JF - B M J (Clinical Research Edition)

ER -

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

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