Wastila Linda, Fu Yu-Hua, Tung Chih Chun, Qato Danya M
Department of Practice, Sciences, and Health Outcomes Research, University of Maryland School of Pharmacy, 220 North Arch Street, 12th Floor, Baltimore, MD, USA.
Peter Lamy Center on Drug Therapy and Aging, University of Maryland School of Pharmacy, Baltimore, MD, USA.
Drugs Real World Outcomes. 2025 Jun 16. doi: 10.1007/s40801-025-00504-y.
Limited research has addressed safety concerns related to vaccination against the human papillomavirus (HPV).
To investigate the association between receipt of HPV vaccination and autonomic dysfunction and menstrual irregularities in girls and young women.
Using a 25% random sample of IQVIA PharMetrics Plus for Academics claims database from 2016 to 2020, we conducted a self-controlled case series study in commercially insured girls and young women receiving their first HPV vaccine dose (analyses conducted between March 2024 and April 2025). Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated for two outcomes-autonomic dysfunction and menstrual irregularities. We conducted further analyses stratified by number of HPV vaccine doses received per beneficiary and by age (9-17 years vs. 18-26 years), as well as adjusted for age as a time-varying covariate. The IRRs were estimated over a maximum risk case post-vaccination period of 36 months compared to a 6-month within-person control pre-vaccination period.
There were 1654 individuals in the autonomic dysfunction cohort and 3140 individuals in the menstrual irregularities cohort. When adjusted for age, HPV vaccination was associated with elevated IRRs for autonomic dysfunction (IRR 1.23; 95% CI 1.08-1.41) and menstrual irregularities (IRR 1.30; 95% CI 1.18-1.43). IRRs for individual outcomes varied by age group, with the younger cohort showing a significantly higher age-adjusted IRR than the older cohort for menstrual irregularities (IRR 1.51; 95% CI 1.33-1.72 vs. IRR 1.15; 95% CI 0.99-1.33, respectively). Although the risk of experiencing autonomic dysfunction was not significant in the adjusted younger cohort, young women aged 18-26 years had a heightened age-adjusted risk (IRR 1.40; 95% CI 1.12-1.75). Findings from the dose-response analysis were inconclusive.
HPV vaccination is associated with elevated risks of autonomic dysfunction and menstrual irregularities, which vary by age. Further research is needed to identify additional risk factors associated with HPV vaccination safety.
针对人乳头瘤病毒（HPV）疫苗接种的安全性问题，相关研究有限。
调查女孩和年轻女性接种HPV疫苗与自主神经功能障碍及月经不调之间的关联。
利用IQVIA PharMetrics Plus for Academics索赔数据库2016年至2020年25%的随机样本，我们对首次接种HPV疫苗的商业保险女孩和年轻女性开展了一项自身对照病例系列研究（分析于2024年3月至2025年4月进行）。针对自主神经功能障碍和月经不调这两个结局估算发病率比（IRR）及95%置信区间（CI）。我们按每位受惠者接种的HPV疫苗剂量数量及年龄（9至17岁与18至26岁）进行分层进一步分析，并将年龄作为时变协变量进行校正。与接种疫苗前6个月的个体内对照期相比，在接种疫苗后最长36个月的最大风险病例期估算IRR。
自主神经功能障碍队列中有1654人，月经不调队列中有3140人。校正年龄后，HPV疫苗接种与自主神经功能障碍（IRR 1.23；95% CI 1.08 - 1.41）及月经不调（IRR 1.30；95% CI 1.18 - 1.43）的发病率比升高相关。各结局的IRR因年龄组而异，较年轻队列在月经不调方面经年龄校正后的IRR显著高于较年长队列（分别为IRR 1.51；95% CI 1.33 - 1.72与IRR 1.15；95% CI 0.99 - 1.33）。虽然在校正后的较年轻队列中出现自主神经功能障碍的风险不显著，但18至26岁的年轻女性经年龄校正后的风险有所增加（IRR 1.40；95% CI 1.12 - 1.75）。剂量反应分析的结果尚无定论。
HPV疫苗接种与自主神经功能障碍及月经不调风险增加相关，且风险因年龄而异。需要进一步研究以确定与HPV疫苗接种安全性相关的其他风险因素。
