四价人乳头瘤病毒（HPV；6、11、16和18型）L1病毒样颗粒疫苗对16至26岁通常未感染HPV的女性因致癌性非疫苗型HPV引起的感染和疾病的影响。

The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years.

作者信息

Brown Darron R, Kjaer Susanne K, Sigurdsson Kristján, Iversen Ole-Erik, Hernandez-Avila Mauricio, Wheeler Cosette M, Perez Gonzalo, Koutsky Laura A, Tay Eng Hseon, Garcia Patricía, Ault Kevin A, Garland Suzanne M, Leodolter Sepp, Olsson Sven-Eric, Tang Grace W K, Ferris Daron G, Paavonen Jorma, Steben Marc, Bosch F Xavier, Dillner Joakim, Joura Elmar A, Kurman Robert J, Majewski Slawomir, Muñoz Nubia, Myers Evan R, Villa Luisa L, Taddeo Frank J, Roberts Christine, Tadesse Amha, Bryan Janine, Lupinacci Lisa C, Giacoletti Katherine E D, Sings Heather L, James Margaret, Hesley Teresa M, Barr Eliav

机构信息

Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

出版信息

J Infect Dis. 2009 Apr 1;199(7):926-35. doi: 10.1086/597307.

DOI:10.1086/597307

PMID:19236279

Abstract

BACKGROUND

Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated.

METHODS

We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotyping was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types.

RESULTS

Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31.

CONCLUSIONS

HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for approximately 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type.

TRIAL REGISTRATION

ClinicalTrials.gov identifiers: NCT00092521 , NCT00092534 , and NCT00092482.

摘要

背景

人乳头瘤病毒（HPV）-6/11/16/18疫苗可降低HPV-6/11/16/18相关的宫颈上皮内瘤变（CIN）1-3或原位腺癌（AIS）的风险。在此，评估了其对与非疫苗致癌HPV类型相关的CIN1-3/AIS的影响。

方法

我们招募了17622名年龄在16-26岁的女性。所有人都定期进行宫颈阴道采样和巴氏试验，长达4年。对活检样本进行HPV基因分型，并由病理专家小组确定组织学诊断。在第1天14种HPV类型呈阴性的受试者中进行分析。预先设定的分析包括持续6个月的感染以及由宫颈癌中HPV 16和18之后的2种和5种最常见HPV类型以及所有检测的非疫苗类型导致的CIN1-3/AIS。

结果

接种疫苗分别使HPV-31/45感染率降低40.3%（95%置信区间[CI]，13.9%至59.0%），CIN1-3/AIS发生率降低43.6%（95%CI，12.9%至64.1%）。HPV-31/33/45/52/58感染率和CIN1-3/AIS的降低率分别为25.0%（95%CI，5.0%至40.9%）和29.2%（95%CI，8.3%至45.5%）。与10种非疫苗HPV类型相关的CIN2-3/AIS的疗效为32.5%（95%CI，6.0%至51.9%）。HPV-31的降低最为显著。