Middeldorp Marit, Duijster Janneke W, Knol Mirjam J, van Benthem Birgit H B, Berkhof Johannes, King Audrey J, de Melker Hester E
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.
BMC Med. 2025 Jun 6;23(1):335. doi: 10.1186/s12916-025-04155-2.
The impact of human papillomavirus (HPV) vaccination programs depends on the degree of indirect protection against new infections achieved among unvaccinated women. We estimated the indirect effect of bivalent HPV vaccination by comparing the HPV-type incidence in unvaccinated female participants between a cohort offered vaccination in 2009/2010 and a cohort of similar-aged women offered vaccination in 2014.
We compared the incidence rates of HPV types in the HAVANA cohort (follow-up from 2010/2011 until 2015/2016) with those from the HAVANA-2 cohort (2017-2022) using two regression approaches to estimate the indirect effect of HPV vaccination. First, we calculated the incidence ratio (IRR) for a vaccine or cross-protective type in HAVANA-2 versus HAVANA by Poisson regression and compared it to the IRR for a non-cross-protective type. The indirect vaccine effect is defined as 1-ratio of the IRRs. Second, we performed Cox regression with infection by vaccine or cross-protective type as the endpoint and calculated the hazard ratio (HR) for HAVANA-2 versus HAVANA after adjusting for time-varying sociodemographic variables. The indirect effect is defined as 1-HR.
We included 661 unvaccinated participants in HAVANA and 927 in HAVANA-2. We observed a significant reduction in incident HPV16 infections of 70.9% (95% CI 48.3-83.7%) with Poisson regression and of 73.1% (95% CI 53.3-84.5%) with Cox regression. For HPV45, significant decreases of 67.3% (95% CI 8.8-88.3%) and 69.8% (95% CI 15.2-89.3%) were observed. For HPV18, HPV31, and HPV33, the indirect effect was not statistically significant.
Large indirect effects of the bivalent HPV vaccination program were observed for HPV16 and HPV45 infections.
人乳头瘤病毒（HPV）疫苗接种计划的影响取决于未接种疫苗的女性中实现的针对新感染的间接保护程度。我们通过比较2009/2010年提供疫苗接种的队列与2014年提供疫苗接种的同龄女性队列中未接种疫苗的女性参与者的HPV型别发病率，估计了二价HPV疫苗接种的间接效果。
我们使用两种回归方法比较了哈瓦那队列（2010/2011年至2015/2016年随访）和哈瓦那-2队列（2017 - 2022年）中HPV型别的发病率，以估计HPV疫苗接种的间接效果。首先，我们通过泊松回归计算哈瓦那-2队列与哈瓦那队列中疫苗或交叉保护型别的发病率比（IRR），并将其与非交叉保护型别的IRR进行比较。间接疫苗效果定义为IRR比值的倒数。其次，我们以疫苗或交叉保护型别的感染为终点进行Cox回归，并在调整随时间变化的社会人口学变量后计算哈瓦那-2队列与哈瓦那队列的风险比（HR）。间接效果定义为1 - HR。
我们纳入了哈瓦那队列中的661名未接种疫苗的参与者和哈瓦那-2队列中的927名未接种疫苗的参与者。通过泊松回归，我们观察到HPV16感染的发病率显著降低了70.9%（95%置信区间48.3 - 83.7%），通过Cox回归降低了73.1%（95%置信区间53.3 - 84.5%）。对于HPV45，观察到显著降低了67.3%（95%置信区间8.8 - 88.3%）和69.8%（95%置信区间15.2 - 89.3%）。对于HPV18、HPV31和HPV33，间接效果无统计学意义。
观察到二价HPV疫苗接种计划对HPV16和HPV45感染有较大的间接效果。
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