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二价人乳头瘤病毒疫苗对荷兰浸润性宫颈癌和宫颈上皮内瘤变3级(CIN3+)的影响:一项基于人群的关联研究。

The effect of bivalent HPV vaccination against invasive cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3+) in the Netherlands: a population-based linkage study.

作者信息

Middeldorp Marit, Brouwer Jesca G M, Duijster Janneke W, Knol Mirjam J, van Kemenade Folkert J, Siebers Albert G, Berkhof Johannes, de Melker Hester E

机构信息

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.

Department of Epidemiology and Data Science, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands.

出版信息

Lancet Reg Health Eur. 2025 May 26;54:101327. doi: 10.1016/j.lanepe.2025.101327. eCollection 2025 Jul.

Abstract

BACKGROUND

The protective effect of HPV vaccination against cervical cancer has been demonstrated in registry linkage studies. The start age of screening in those studies was lower than 25 years. We aimed to estimate the effectiveness of bivalent HPV16/18 vaccination against invasive cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3+) in the Netherlands, where routine screening starts at age 30 years.

METHODS

We linked the vaccination status of women born in 1993 who were eligible for HPV vaccination at age 16 years with histopathological results recorded until April 1, 2024, in the nationwide pathology databank (Palga). Cumulative risks of invasive cervical cancer and CIN3+ were estimated for fully vaccinated (3 doses or 2 doses ≥150 days apart), partially vaccinated, and unvaccinated women. Cumulative risk ratios (CRRs) were adjusted for differences in screening participation between vaccine groups.

FINDINGS

A total of 103,059 women were included, of whom 47,130 were fully vaccinated, 5098 partially vaccinated, and 50,831 unvaccinated. Five cancers (0·011%) were observed in fully vaccinated, two (0·039%) in partially vaccinated, and 42 (0·083%) in unvaccinated women. The CRR for fully vaccinated women compared with unvaccinated women was 0·085 (95% confidence interval 0·025, 0·24) for cancer and 0·19 (0·16, 0·23) for CIN3+. The CRR for partially vaccinated women was 0·52 (0·12, 1·71) for cancer and 0·42 (0·30, 0·57) for CIN3+.

INTERPRETATION

The risk of cervical cancer and CIN3+ was strongly reduced in vaccinated women indicating that vaccine protection extends at least until age 30.

FUNDING

The Dutch Ministry of Health, Welfare, and Sport.

摘要

背景

人乳头瘤病毒(HPV)疫苗对宫颈癌的保护作用已在登记关联研究中得到证实。这些研究中的筛查起始年龄低于25岁。我们旨在评估二价HPV16/18疫苗在荷兰预防浸润性宫颈癌和宫颈上皮内瘤变3级(CIN3+)的有效性,在荷兰常规筛查从30岁开始。

方法

我们将1993年出生、16岁时符合HPV疫苗接种条件的女性的疫苗接种状况与截至2024年4月1日在全国病理数据库(Palga)中记录的组织病理学结果相联系。估计完全接种(3剂或2剂且间隔≥150天)、部分接种和未接种疫苗女性发生浸润性宫颈癌和CIN3+的累积风险。对疫苗组之间筛查参与率的差异调整累积风险比(CRR)。

结果

共纳入103,059名女性,其中47,130名完全接种,5098名部分接种,50,831名未接种。完全接种疫苗的女性中观察到5例癌症(0.011%),部分接种疫苗的女性中观察到2例(0.039%),未接种疫苗的女性中观察到42例(0.083%)。完全接种疫苗的女性与未接种疫苗的女性相比,癌症的CRR为0.085(95%置信区间0.025,0.24),CIN3+的CRR为0.19(0.16,0.23)。部分接种疫苗的女性癌症的CRR为0.52(0.12,1.71),CIN3+的CRR为0.42(0.30,0.57)。

解读

接种疫苗的女性患宫颈癌和CIN3+的风险大幅降低,表明疫苗保护作用至少持续到30岁。

资助

荷兰卫生、福利和体育部。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92a3/12153372/1d9501c56b57/gr1.jpg

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