Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection

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

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Objective: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL®/SILGARD®) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed. Results: Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrollment. Methods: 18,174 women were enrolled into three clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for ≥1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment. Conclusions: These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.

Original languageEnglish (US)
Pages (from-to)696-704
Number of pages9
JournalHuman Vaccines
Volume5
Issue number10
DOIs
StatePublished - Dec 1 2009

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Human papillomavirus 11
Human papillomavirus 6
Papillomavirus Vaccines
Vaccines
Infection
DNA
Placebos
DNA Vaccines
Serology
Population

Keywords

  • Cervical cancer
  • HPV
  • Vaccine

ASJC Scopus subject areas

  • Immunology
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection. / Olsson, Sven Eric; Kjaer, Susanne K.; Sigurdsson, Kristján; Iversen, Ole Erik; Hernandez-Avila, Mauricio; Wheeler, Cosette M.; Perez, Gonzalo; Brown, Darron R.; Koutsky, Laura A.; Tay, Eng Hseon; García, Patricia; Ault, Kevin A.; Garland, Suzanne M.; Leodolter, Sepp; Tang, Grace W.K.; Ferris, Daron Gale; Paavonen, Jorma; Lehtinen, Matti; Steben, Marc; Bosch, F. Xavier; Dillner, Joakim; Joura, Elmar A.; Majewski, Slawomir; Muñoz, Nubia; Myers, Evan R.; Villa, Luisa L.; Taddeo, Frank J.; Roberts, Christine; Tadesse, Amha; Bryan, Janine; Maansson, Roger; Vuocolo, Scott; Hesley, Teresa M.; Saah, Alfred; Barr, Eliav; Haupt, Richard M.

In: Human Vaccines, Vol. 5, No. 10, 01.12.2009, p. 696-704.

Research output: Contribution to journalArticle

Olsson, SE, Kjaer, SK, Sigurdsson, K, Iversen, OE, Hernandez-Avila, M, Wheeler, CM, Perez, G, Brown, DR, Koutsky, LA, Tay, EH, García, P, Ault, KA, Garland, SM, Leodolter, S, Tang, GWK, Ferris, DG, Paavonen, J, Lehtinen, M, Steben, M, Bosch, FX, Dillner, J, Joura, EA, Majewski, S, Muñoz, N, Myers, ER, Villa, LL, Taddeo, FJ, Roberts, C, Tadesse, A, Bryan, J, Maansson, R, Vuocolo, S, Hesley, TM, Saah, A, Barr, E & Haupt, RM 2009, 'Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection', Human Vaccines, vol. 5, no. 10, pp. 696-704. https://doi.org/10.4161/hv.5.10.9515
Olsson, Sven Eric ; Kjaer, Susanne K. ; Sigurdsson, Kristján ; Iversen, Ole Erik ; Hernandez-Avila, Mauricio ; Wheeler, Cosette M. ; Perez, Gonzalo ; Brown, Darron R. ; Koutsky, Laura A. ; Tay, Eng Hseon ; García, Patricia ; Ault, Kevin A. ; Garland, Suzanne M. ; Leodolter, Sepp ; Tang, Grace W.K. ; Ferris, Daron Gale ; Paavonen, Jorma ; Lehtinen, Matti ; Steben, Marc ; Bosch, F. Xavier ; Dillner, Joakim ; Joura, Elmar A. ; Majewski, Slawomir ; Muñoz, Nubia ; Myers, Evan R. ; Villa, Luisa L. ; Taddeo, Frank J. ; Roberts, Christine ; Tadesse, Amha ; Bryan, Janine ; Maansson, Roger ; Vuocolo, Scott ; Hesley, Teresa M. ; Saah, Alfred ; Barr, Eliav ; Haupt, Richard M. / Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection. In: Human Vaccines. 2009 ; Vol. 5, No. 10. pp. 696-704.
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TY - JOUR

T1 - Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection

AU - Olsson, Sven Eric

AU - Kjaer, Susanne K.

AU - Sigurdsson, Kristján

AU - Iversen, Ole Erik

AU - Hernandez-Avila, Mauricio

AU - Wheeler, Cosette M.

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 - Tang, Grace W.K.

AU - Ferris, Daron Gale

AU - Paavonen, Jorma

AU - Lehtinen, Matti

AU - Steben, Marc

AU - Bosch, F. Xavier

AU - Dillner, Joakim

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

AU - Maansson, Roger

AU - Vuocolo, Scott

AU - Hesley, Teresa M.

AU - Saah, Alfred

AU - Barr, Eliav

AU - Haupt, Richard M.

PY - 2009/12/1

Y1 - 2009/12/1

N2 - Objective: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL®/SILGARD®) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed. Results: Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrollment. Methods: 18,174 women were enrolled into three clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for ≥1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment. Conclusions: These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.

AB - Objective: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL®/SILGARD®) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed. Results: Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrollment. Methods: 18,174 women were enrolled into three clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for ≥1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment. Conclusions: These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.

KW - Cervical cancer

KW - HPV

KW - Vaccine

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