Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: A randomized controlled trial

Constance Mao, Laura A. Koutsky, Kevin A. Ault, Cosette M. Wheeler, Darron Brown, Dorothy J. Wiley, Frances B. Alvarez, Oliver M. Bautista, Kathrin U. Jansen, Eliav Barr

Research output: Contribution to journalArticle

412 Citations (Scopus)

Abstract

OBJECTIVE: Human papillomavirus (HPV) virus-like particle (VLP) vaccines have demonstrated effectiveness in preventing persistent HPV infections. Whether protection lasts longer than 18 months and, thus, impacts rates of cervical intraepithelial neoplasia (CIN) 2-3 has not yet been established. We present results from an HPV16 L1 VLP vaccine trial through 48 months. METHODS: A total of 2,391 women, aged 16-23 years, participated in a randomized, double-blind, placebo-controlled trial. Either 40 μg HPV16 L1 VLP vaccine or placebo was given intramuscularly at day 1, month 2, and month 6. Genital samples for HPV16 DNA and Pap tests were obtained at day 1, month 7, and then 6-monthly through month 48. Colposcopy and cervical biopsies were performed if clinically indicated and at study exit. Serum HPV16 antibody titer was measured by radioimmunoassay. RESULTS: Among 750 placebo recipients in the per protocol population, 12 women developed HPV16-related CIN2-3 (6 CIN2 and 6 CIN3). Among 755 vaccine recipients, there were no cases (vaccine efficacy 100%, 95% confidence interval [CI] 65-100%). There were 111 cases of persistent HPV16 infection in placebo recipients and 7 cases in vaccine recipients (vaccine efficacy 94%, 95% CI 88-98%). After immunization, HPV16 serum antibody geometric mean titers peaked at month 7 (1,519 milliMerck units [mMU]/mL), declined through month 18 (202 mMU/mL), and remained relatively stable between month 30 and month 48 (128-150 mMU/mL). CONCLUSION: The vaccine HPV16 L1 VLP provides high-level protection against persistent HPV16 infection and HPV16-related CIN2-3 for at least 3.5 years after immunization. Administration of L1 VLP vaccines targeting HPV16 is likely to reduce risk for cervical cancer.

Original languageEnglish (US)
Pages (from-to)18-27
Number of pages10
JournalObstetrics and Gynecology
Volume107
Issue number1
StatePublished - Jan 2006
Externally publishedYes

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Papillomavirus Vaccines
Virus-Like Particle Vaccines
Cervical Intraepithelial Neoplasia
Human papillomavirus 16
Vaccines
Randomized Controlled Trials
Placebos
Papillomaviridae
Immunization
Confidence Intervals
Papanicolaou Test
Colposcopy
Papillomavirus Infections
Antibodies
Infection
Serum
Uterine Cervical Neoplasms
Virion
Radioimmunoassay
Biopsy

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Mao, C., Koutsky, L. A., Ault, K. A., Wheeler, C. M., Brown, D., Wiley, D. J., ... Barr, E. (2006). Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: A randomized controlled trial. Obstetrics and Gynecology, 107(1), 18-27.

Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia : A randomized controlled trial. / Mao, Constance; Koutsky, Laura A.; Ault, Kevin A.; Wheeler, Cosette M.; Brown, Darron; Wiley, Dorothy J.; Alvarez, Frances B.; Bautista, Oliver M.; Jansen, Kathrin U.; Barr, Eliav.

In: Obstetrics and Gynecology, Vol. 107, No. 1, 01.2006, p. 18-27.

Research output: Contribution to journalArticle

Mao, C, Koutsky, LA, Ault, KA, Wheeler, CM, Brown, D, Wiley, DJ, Alvarez, FB, Bautista, OM, Jansen, KU & Barr, E 2006, 'Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: A randomized controlled trial', Obstetrics and Gynecology, vol. 107, no. 1, pp. 18-27.
Mao, Constance ; Koutsky, Laura A. ; Ault, Kevin A. ; Wheeler, Cosette M. ; Brown, Darron ; Wiley, Dorothy J. ; Alvarez, Frances B. ; Bautista, Oliver M. ; Jansen, Kathrin U. ; Barr, Eliav. / Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia : A randomized controlled trial. In: Obstetrics and Gynecology. 2006 ; Vol. 107, No. 1. pp. 18-27.
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abstract = "OBJECTIVE: Human papillomavirus (HPV) virus-like particle (VLP) vaccines have demonstrated effectiveness in preventing persistent HPV infections. Whether protection lasts longer than 18 months and, thus, impacts rates of cervical intraepithelial neoplasia (CIN) 2-3 has not yet been established. We present results from an HPV16 L1 VLP vaccine trial through 48 months. METHODS: A total of 2,391 women, aged 16-23 years, participated in a randomized, double-blind, placebo-controlled trial. Either 40 μg HPV16 L1 VLP vaccine or placebo was given intramuscularly at day 1, month 2, and month 6. Genital samples for HPV16 DNA and Pap tests were obtained at day 1, month 7, and then 6-monthly through month 48. Colposcopy and cervical biopsies were performed if clinically indicated and at study exit. Serum HPV16 antibody titer was measured by radioimmunoassay. RESULTS: Among 750 placebo recipients in the per protocol population, 12 women developed HPV16-related CIN2-3 (6 CIN2 and 6 CIN3). Among 755 vaccine recipients, there were no cases (vaccine efficacy 100{\%}, 95{\%} confidence interval [CI] 65-100{\%}). There were 111 cases of persistent HPV16 infection in placebo recipients and 7 cases in vaccine recipients (vaccine efficacy 94{\%}, 95{\%} CI 88-98{\%}). After immunization, HPV16 serum antibody geometric mean titers peaked at month 7 (1,519 milliMerck units [mMU]/mL), declined through month 18 (202 mMU/mL), and remained relatively stable between month 30 and month 48 (128-150 mMU/mL). CONCLUSION: The vaccine HPV16 L1 VLP provides high-level protection against persistent HPV16 infection and HPV16-related CIN2-3 for at least 3.5 years after immunization. Administration of L1 VLP vaccines targeting HPV16 is likely to reduce risk for cervical cancer.",
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AU - Koutsky, Laura A.

AU - Ault, Kevin A.

AU - Wheeler, Cosette M.

AU - Brown, Darron

AU - Wiley, Dorothy J.

AU - Alvarez, Frances B.

AU - Bautista, Oliver M.

AU - Jansen, Kathrin U.

AU - Barr, Eliav

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N2 - OBJECTIVE: Human papillomavirus (HPV) virus-like particle (VLP) vaccines have demonstrated effectiveness in preventing persistent HPV infections. Whether protection lasts longer than 18 months and, thus, impacts rates of cervical intraepithelial neoplasia (CIN) 2-3 has not yet been established. We present results from an HPV16 L1 VLP vaccine trial through 48 months. METHODS: A total of 2,391 women, aged 16-23 years, participated in a randomized, double-blind, placebo-controlled trial. Either 40 μg HPV16 L1 VLP vaccine or placebo was given intramuscularly at day 1, month 2, and month 6. Genital samples for HPV16 DNA and Pap tests were obtained at day 1, month 7, and then 6-monthly through month 48. Colposcopy and cervical biopsies were performed if clinically indicated and at study exit. Serum HPV16 antibody titer was measured by radioimmunoassay. RESULTS: Among 750 placebo recipients in the per protocol population, 12 women developed HPV16-related CIN2-3 (6 CIN2 and 6 CIN3). Among 755 vaccine recipients, there were no cases (vaccine efficacy 100%, 95% confidence interval [CI] 65-100%). There were 111 cases of persistent HPV16 infection in placebo recipients and 7 cases in vaccine recipients (vaccine efficacy 94%, 95% CI 88-98%). After immunization, HPV16 serum antibody geometric mean titers peaked at month 7 (1,519 milliMerck units [mMU]/mL), declined through month 18 (202 mMU/mL), and remained relatively stable between month 30 and month 48 (128-150 mMU/mL). CONCLUSION: The vaccine HPV16 L1 VLP provides high-level protection against persistent HPV16 infection and HPV16-related CIN2-3 for at least 3.5 years after immunization. Administration of L1 VLP vaccines targeting HPV16 is likely to reduce risk for cervical cancer.

AB - OBJECTIVE: Human papillomavirus (HPV) virus-like particle (VLP) vaccines have demonstrated effectiveness in preventing persistent HPV infections. Whether protection lasts longer than 18 months and, thus, impacts rates of cervical intraepithelial neoplasia (CIN) 2-3 has not yet been established. We present results from an HPV16 L1 VLP vaccine trial through 48 months. METHODS: A total of 2,391 women, aged 16-23 years, participated in a randomized, double-blind, placebo-controlled trial. Either 40 μg HPV16 L1 VLP vaccine or placebo was given intramuscularly at day 1, month 2, and month 6. Genital samples for HPV16 DNA and Pap tests were obtained at day 1, month 7, and then 6-monthly through month 48. Colposcopy and cervical biopsies were performed if clinically indicated and at study exit. Serum HPV16 antibody titer was measured by radioimmunoassay. RESULTS: Among 750 placebo recipients in the per protocol population, 12 women developed HPV16-related CIN2-3 (6 CIN2 and 6 CIN3). Among 755 vaccine recipients, there were no cases (vaccine efficacy 100%, 95% confidence interval [CI] 65-100%). There were 111 cases of persistent HPV16 infection in placebo recipients and 7 cases in vaccine recipients (vaccine efficacy 94%, 95% CI 88-98%). After immunization, HPV16 serum antibody geometric mean titers peaked at month 7 (1,519 milliMerck units [mMU]/mL), declined through month 18 (202 mMU/mL), and remained relatively stable between month 30 and month 48 (128-150 mMU/mL). CONCLUSION: The vaccine HPV16 L1 VLP provides high-level protection against persistent HPV16 infection and HPV16-related CIN2-3 for at least 3.5 years after immunization. Administration of L1 VLP vaccines targeting HPV16 is likely to reduce risk for cervical cancer.

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