Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years

被引：292

作者：

Romanowski, B. ^{[1
]}

de Borba, P. Colares ^{[2
]}

Naud, P. S. ^{[3
]}

Roteli-Martins, C. M. ^{[4
]}

De Carvalho, N. S. ^{[5
,6
]}

Teixeira, J. C. ^{[7
]}

Aoki, F. ^{[8
]}

Ramjattan, B. ^{[9
]}

Shier, R. M. ^{[10
]}

Somani, R. ^{[11
]}

Barbier, S. ^{[12
]}

Blatter, M. M. ^{[13
]}

Chambers, C. ^{[14
]}

Ferris, D. ^{[15
]}

Gall, S. A. ^{[16
]}

Guerra, F. A. ^{[17
]}

Harper, D. M. ^{[18
]}

Hedrick, J. A. ^{[19
]}

Henry, D. C. ^{[20
]}

Korn, A. P. ^{[21
]}

Kroll, R. ^{[22
]}

Moscicki, A-B ^{[23
]}

Rosenfeld, W. D. ^{[24
]}

Sullivan, B. J. ^{[25
]}

Thoming, C. S. ^{[26
]}

Tyring, S. K. ^{[27
]}

Wheeler, C. M. ^{[28
]}

Dubin, G. ^{[29
]}

Schuind, A. ^{[29
]}

Zahaf, T. ^{[30
]}

机构：

[1] Univ Alberta, Edmonton, AB T6G 2C8, Canada

[2] Ceara Canc Prevent Inst, Fortaleza, Ceara, Brazil

[3] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil

[4] Leonor Mendes de Barros Hosp, Hlth State Dept, Sao Paulo, Brazil

[5] Univ Fed Parana, Dept Obstet & Gynaecol, BR-80060000 Curitiba, Parana, Brazil

[6] Clin Hosp, Obstetr Gynecol & Infect Dis Sector, Curitiba, Parana, Brazil

[7] Univ Estadual Campinas, CAISM, Dept Gynaecol, Div Oncol, Campinas, SP, Brazil

[8] Univ Manitoba, Winnipeg, MB, Canada

[9] Cowan Ave Med Clin, St John, NF, Canada

[10] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada

[11] Glover Med Clin, Langley, BC, Canada

[12] Womens Clin Res Ctr, Seattle, WA USA

[13] Primary Phys Res, Pittsburgh, PA USA

[14] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA

[15] Med Coll Georgia, Augusta, GA 30912 USA

[16] Univ Louisville, Sch Med, Louisville, KY 40292 USA

[17] San Antonio Metropolitan Hlth Dist, San Antonio, TX USA

[18] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA

[19] Kentucky Pediat & Adult Res, Bardstow, KY USA

[20] J Lewis Res, Salt Lake City, UT USA

[21] San Francisco Gen Hosp, San Francisco, CA 94110 USA

[22] Womens Clin Res Ctr, Seattle, WA USA

[23] Univ Calif San Francisco, San Francisco, CA 94143 USA

[24] Goryeb Childrens Hosp, Atlantic Hlth, Dept Pediat, Morristown, NJ USA

[25] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA

[26] Westover Hts Clin, Portland, OR USA

[27] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA

[28] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA

[29] GSK Biol, King Of Prussia, PA USA

[30] GSK Biol, Rixensart, Belgium

来源：

LANCET | 2009年 / 374卷 / 9706期

关键词：

SUBSEQUENT HPV INFECTION; PARTICLE VACCINE; CERVICAL-CANCER; YOUNG-WOMEN; NATURAL-HISTORY; ANTIBODY-LEVELS; DOUBLE-BLIND; HEPATITIS-B; TYPE-16; RISK;

D O I：

10.1016/S0140-6736(09)61567-1

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. Methods Women aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848. Findings For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% C1 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. Interpretation Our findings show excellent long-term efficacy, high and sustained immunogenicity and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years.

引用

页码：1975 / 1985

页数：11