Mao Constance, Koutsky Laura A, Ault Kevin A, Wheeler Cosette M, Brown Darron R, Wiley Dorothy J, Alvarez Frances B, Bautista Oliver M, Jansen Kathrin U, Barr Eliav
Department of Obstetrics and Gynecology and Epidemiology, University of Washington, Seattle, Washington 98104-2499, USA.
Obstet Gynecol. 2006 Jan;107(1):18-27. doi: 10.1097/01.AOG.0000192397.41191.fb.
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.
A total of 2,391 women, aged 16-23 years, participated in a randomized, double-blind, placebo-controlled trial. Either 40 mug 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.
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 milli-Merck units [mMU]/mL), declined through month 18 (202 mMU/mL), and remained relatively stable between month 30 and month 48 (128-150 mMU/mL).
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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人乳头瘤病毒（HPV）病毒样颗粒（VLP）疫苗已证明在预防持续性HPV感染方面有效。其保护作用是否能持续超过18个月，进而影响宫颈上皮内瘤变（CIN）2 - 3的发生率尚未明确。我们展示了一项HPV16 L1 VLP疫苗试验48个月的结果。
共有2391名年龄在16 - 23岁的女性参与了一项随机、双盲、安慰剂对照试验。在第1天、第2个月和第6个月时，分别肌肉注射40μg HPV16 L1 VLP疫苗或安慰剂。在第1天、第7个月，随后每6个月直至第48个月采集HPV16 DNA和巴氏试验的生殖道样本。如有临床指征且在研究结束时进行阴道镜检查和宫颈活检。通过放射免疫测定法测量血清HPV16抗体滴度。
在意向性分析人群中的750名安慰剂接受者中，12名女性发生了HPV16相关的CIN2 - 3（6例CIN2和6例CIN3）。在755名疫苗接受者中，无病例发生（疫苗效力100%，95%置信区间[CI] 65 - 100%）。安慰剂接受者中有111例持续性HPV16感染病例，疫苗接受者中有7例（疫苗效力94%，95% CI 88 - 98%）。免疫后，HPV16血清抗体几何平均滴度在第7个月达到峰值（1519毫默克单位[mMU]/mL），在第18个月下降至（202 mMU/mL），并在第30个月至第48个月之间保持相对稳定（128 - 150 mMU/mL）。
HPV16 L1 VLP疫苗在免疫后至少3.5年内为持续性HPV16感染和HPV16相关的CIN2 - 3提供高水平保护。接种针对HPV16的L1 VLP疫苗可能会降低宫颈癌风险。
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