HPV vaccine against anal HPV infection and anal intraepithelial neoplasia

Joel M. Palefsky, Anna R. Giuliano, Stephen Goldstone, Edson D. Moreira, Carlos Aranda, Heiko Jessen, Richard Hillman, Daron Ferris, Francois Coutlee, Mark H. Stoler, J. Brooke Marshall, David Radley, Scott Vuocolo, Richard M. Haupt, Dalya Guris, Elizabeth I.O. Garner

Research output: Contribution to journalArticle

518 Citations (Scopus)

Abstract

Background: The rate of anal cancer is increasing among both women and men, particularly men who have sex with men. Caused by infection with human papillomavirus (HPV), primarily HPV type 16 or 18, anal cancer is preceded by high-grade anal intraepithelial neoplasia (grade 2 or 3). We studied the safety and efficacy of quadrivalent HPV vaccine (qHPV) against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 infection in men who have sex with men. Methods: In a substudy of a larger double-blind study, we randomly assigned 602 healthy men who have sex with men, 16 to 26 years of age, to receive either qHPV or placebo. The primary efficacy objective was prevention of anal intraepithelial neoplasia or anal cancer related to infection with HPV-6, 11, 16, or 18. Efficacy analyses were performed in intention-totreat and per-protocol efficacy populations. The rates of adverse events were documented. Results: Efficacy of the qHPV vaccine against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 was 50.3% (95% confidence interval [CI], 25.7 to 67.2) in the intention-to-treat population and 77.5% (95% CI, 39.6 to 93.3) in the per-protocol efficacy population; the corresponding efficacies against anal intraepithelial neoplasia associated with HPV of any type were 25.7% (95% CI, -1.1 to 45.6) and 54.9% (95% CI, 8.4 to 79.1), respectively. Rates of anal intraepithelial neoplasia per 100 person-years were 17.5 in the placebo group and 13.0 in the vaccine group in the intention-to-treat population and 8.9 in the placebo group and 4.0 in the vaccine group in the per-protocol efficacy population. The rate of grade 2 or 3 anal intraepithelial neoplasia related to infection with HPV-6, 11, 16, or 18 was reduced by 54.2% (95% CI, 18.0 to 75.3) in the intention-to-treat population and by 74.9% (95% CI, 8.8 to 95.4) in the per-protocol efficacy population. The corresponding risks of persistent anal infection with HPV-6, 11, 16, or 18 were reduced by 59.4% (95% CI, 43.0 to 71.4) and 94.9% (95% CI, 80.4 to 99.4), respectively. No vaccine-related serious adverse events were reported. Conclusions: Use of the qHPV vaccine reduced the rates of anal intraepithelial neoplasia, including of grade 2 or 3, among men who have sex with men. The vaccine had a favorable safety profile and may help to reduce the risk of anal cancer.

Original languageEnglish (US)
Pages (from-to)1576-1585
Number of pages10
JournalNew England Journal of Medicine
Volume365
Issue number17
DOIs
StatePublished - Oct 27 2011

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Papillomavirus Vaccines
Papillomavirus Infections
Human papillomavirus 11
Human papillomavirus 6
Confidence Intervals
Anus Neoplasms
Vaccines
Neoplasms
Population
Infection
Placebos
Safety
Human papillomavirus 18
Human papillomavirus 16
Double-Blind Method

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Palefsky, J. M., Giuliano, A. R., Goldstone, S., Moreira, E. D., Aranda, C., Jessen, H., ... Garner, E. I. O. (2011). HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. New England Journal of Medicine, 365(17), 1576-1585. https://doi.org/10.1056/NEJMoa1010971

HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. / Palefsky, Joel M.; Giuliano, Anna R.; Goldstone, Stephen; Moreira, Edson D.; Aranda, Carlos; Jessen, Heiko; Hillman, Richard; Ferris, Daron; Coutlee, Francois; Stoler, Mark H.; Marshall, J. Brooke; Radley, David; Vuocolo, Scott; Haupt, Richard M.; Guris, Dalya; Garner, Elizabeth I.O.

In: New England Journal of Medicine, Vol. 365, No. 17, 27.10.2011, p. 1576-1585.

Research output: Contribution to journalArticle

Palefsky, JM, Giuliano, AR, Goldstone, S, Moreira, ED, Aranda, C, Jessen, H, Hillman, R, Ferris, D, Coutlee, F, Stoler, MH, Marshall, JB, Radley, D, Vuocolo, S, Haupt, RM, Guris, D & Garner, EIO 2011, 'HPV vaccine against anal HPV infection and anal intraepithelial neoplasia', New England Journal of Medicine, vol. 365, no. 17, pp. 1576-1585. https://doi.org/10.1056/NEJMoa1010971
Palefsky JM, Giuliano AR, Goldstone S, Moreira ED, Aranda C, Jessen H et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. New England Journal of Medicine. 2011 Oct 27;365(17):1576-1585. https://doi.org/10.1056/NEJMoa1010971
Palefsky, Joel M. ; Giuliano, Anna R. ; Goldstone, Stephen ; Moreira, Edson D. ; Aranda, Carlos ; Jessen, Heiko ; Hillman, Richard ; Ferris, Daron ; Coutlee, Francois ; Stoler, Mark H. ; Marshall, J. Brooke ; Radley, David ; Vuocolo, Scott ; Haupt, Richard M. ; Guris, Dalya ; Garner, Elizabeth I.O. / HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. In: New England Journal of Medicine. 2011 ; Vol. 365, No. 17. pp. 1576-1585.
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title = "HPV vaccine against anal HPV infection and anal intraepithelial neoplasia",
abstract = "Background: The rate of anal cancer is increasing among both women and men, particularly men who have sex with men. Caused by infection with human papillomavirus (HPV), primarily HPV type 16 or 18, anal cancer is preceded by high-grade anal intraepithelial neoplasia (grade 2 or 3). We studied the safety and efficacy of quadrivalent HPV vaccine (qHPV) against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 infection in men who have sex with men. Methods: In a substudy of a larger double-blind study, we randomly assigned 602 healthy men who have sex with men, 16 to 26 years of age, to receive either qHPV or placebo. The primary efficacy objective was prevention of anal intraepithelial neoplasia or anal cancer related to infection with HPV-6, 11, 16, or 18. Efficacy analyses were performed in intention-totreat and per-protocol efficacy populations. The rates of adverse events were documented. Results: Efficacy of the qHPV vaccine against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 was 50.3{\%} (95{\%} confidence interval [CI], 25.7 to 67.2) in the intention-to-treat population and 77.5{\%} (95{\%} CI, 39.6 to 93.3) in the per-protocol efficacy population; the corresponding efficacies against anal intraepithelial neoplasia associated with HPV of any type were 25.7{\%} (95{\%} CI, -1.1 to 45.6) and 54.9{\%} (95{\%} CI, 8.4 to 79.1), respectively. Rates of anal intraepithelial neoplasia per 100 person-years were 17.5 in the placebo group and 13.0 in the vaccine group in the intention-to-treat population and 8.9 in the placebo group and 4.0 in the vaccine group in the per-protocol efficacy population. The rate of grade 2 or 3 anal intraepithelial neoplasia related to infection with HPV-6, 11, 16, or 18 was reduced by 54.2{\%} (95{\%} CI, 18.0 to 75.3) in the intention-to-treat population and by 74.9{\%} (95{\%} CI, 8.8 to 95.4) in the per-protocol efficacy population. The corresponding risks of persistent anal infection with HPV-6, 11, 16, or 18 were reduced by 59.4{\%} (95{\%} CI, 43.0 to 71.4) and 94.9{\%} (95{\%} CI, 80.4 to 99.4), respectively. No vaccine-related serious adverse events were reported. Conclusions: Use of the qHPV vaccine reduced the rates of anal intraepithelial neoplasia, including of grade 2 or 3, among men who have sex with men. The vaccine had a favorable safety profile and may help to reduce the risk of anal cancer.",
author = "Palefsky, {Joel M.} and Giuliano, {Anna R.} and Stephen Goldstone and Moreira, {Edson D.} and Carlos Aranda and Heiko Jessen and Richard Hillman and Daron Ferris and Francois Coutlee and Stoler, {Mark H.} and Marshall, {J. Brooke} and David Radley and Scott Vuocolo and Haupt, {Richard M.} and Dalya Guris and Garner, {Elizabeth I.O.}",
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TY - JOUR

T1 - HPV vaccine against anal HPV infection and anal intraepithelial neoplasia

AU - Palefsky, Joel M.

AU - Giuliano, Anna R.

AU - Goldstone, Stephen

AU - Moreira, Edson D.

AU - Aranda, Carlos

AU - Jessen, Heiko

AU - Hillman, Richard

AU - Ferris, Daron

AU - Coutlee, Francois

AU - Stoler, Mark H.

AU - Marshall, J. Brooke

AU - Radley, David

AU - Vuocolo, Scott

AU - Haupt, Richard M.

AU - Guris, Dalya

AU - Garner, Elizabeth I.O.

PY - 2011/10/27

Y1 - 2011/10/27

N2 - Background: The rate of anal cancer is increasing among both women and men, particularly men who have sex with men. Caused by infection with human papillomavirus (HPV), primarily HPV type 16 or 18, anal cancer is preceded by high-grade anal intraepithelial neoplasia (grade 2 or 3). We studied the safety and efficacy of quadrivalent HPV vaccine (qHPV) against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 infection in men who have sex with men. Methods: In a substudy of a larger double-blind study, we randomly assigned 602 healthy men who have sex with men, 16 to 26 years of age, to receive either qHPV or placebo. The primary efficacy objective was prevention of anal intraepithelial neoplasia or anal cancer related to infection with HPV-6, 11, 16, or 18. Efficacy analyses were performed in intention-totreat and per-protocol efficacy populations. The rates of adverse events were documented. Results: Efficacy of the qHPV vaccine against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 was 50.3% (95% confidence interval [CI], 25.7 to 67.2) in the intention-to-treat population and 77.5% (95% CI, 39.6 to 93.3) in the per-protocol efficacy population; the corresponding efficacies against anal intraepithelial neoplasia associated with HPV of any type were 25.7% (95% CI, -1.1 to 45.6) and 54.9% (95% CI, 8.4 to 79.1), respectively. Rates of anal intraepithelial neoplasia per 100 person-years were 17.5 in the placebo group and 13.0 in the vaccine group in the intention-to-treat population and 8.9 in the placebo group and 4.0 in the vaccine group in the per-protocol efficacy population. The rate of grade 2 or 3 anal intraepithelial neoplasia related to infection with HPV-6, 11, 16, or 18 was reduced by 54.2% (95% CI, 18.0 to 75.3) in the intention-to-treat population and by 74.9% (95% CI, 8.8 to 95.4) in the per-protocol efficacy population. The corresponding risks of persistent anal infection with HPV-6, 11, 16, or 18 were reduced by 59.4% (95% CI, 43.0 to 71.4) and 94.9% (95% CI, 80.4 to 99.4), respectively. No vaccine-related serious adverse events were reported. Conclusions: Use of the qHPV vaccine reduced the rates of anal intraepithelial neoplasia, including of grade 2 or 3, among men who have sex with men. The vaccine had a favorable safety profile and may help to reduce the risk of anal cancer.

AB - Background: The rate of anal cancer is increasing among both women and men, particularly men who have sex with men. Caused by infection with human papillomavirus (HPV), primarily HPV type 16 or 18, anal cancer is preceded by high-grade anal intraepithelial neoplasia (grade 2 or 3). We studied the safety and efficacy of quadrivalent HPV vaccine (qHPV) against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 infection in men who have sex with men. Methods: In a substudy of a larger double-blind study, we randomly assigned 602 healthy men who have sex with men, 16 to 26 years of age, to receive either qHPV or placebo. The primary efficacy objective was prevention of anal intraepithelial neoplasia or anal cancer related to infection with HPV-6, 11, 16, or 18. Efficacy analyses were performed in intention-totreat and per-protocol efficacy populations. The rates of adverse events were documented. Results: Efficacy of the qHPV vaccine against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 was 50.3% (95% confidence interval [CI], 25.7 to 67.2) in the intention-to-treat population and 77.5% (95% CI, 39.6 to 93.3) in the per-protocol efficacy population; the corresponding efficacies against anal intraepithelial neoplasia associated with HPV of any type were 25.7% (95% CI, -1.1 to 45.6) and 54.9% (95% CI, 8.4 to 79.1), respectively. Rates of anal intraepithelial neoplasia per 100 person-years were 17.5 in the placebo group and 13.0 in the vaccine group in the intention-to-treat population and 8.9 in the placebo group and 4.0 in the vaccine group in the per-protocol efficacy population. The rate of grade 2 or 3 anal intraepithelial neoplasia related to infection with HPV-6, 11, 16, or 18 was reduced by 54.2% (95% CI, 18.0 to 75.3) in the intention-to-treat population and by 74.9% (95% CI, 8.8 to 95.4) in the per-protocol efficacy population. The corresponding risks of persistent anal infection with HPV-6, 11, 16, or 18 were reduced by 59.4% (95% CI, 43.0 to 71.4) and 94.9% (95% CI, 80.4 to 99.4), respectively. No vaccine-related serious adverse events were reported. Conclusions: Use of the qHPV vaccine reduced the rates of anal intraepithelial neoplasia, including of grade 2 or 3, among men who have sex with men. The vaccine had a favorable safety profile and may help to reduce the risk of anal cancer.

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