Hviid Anders, Myrup Thiesson Emilia
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Pharmacovigilance Research Center, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
JAMA Netw Open. 2021 Aug 2;4(8):e2120391. doi: 10.1001/jamanetworkopen.2021.20391.
Anecdotal case reports have suggested an association between human papillomavirus (HPV) vaccination and primary ovarian insufficiency, but observational studies of HPV and primary ovarian insufficiency are rare, and their findings do not support an association. However, available studies have been limited by statistical power, and concerns about infertility after vaccination are associated with lower levels of uptake of the cancer-preventing vaccine in many countries.
To evaluate the risk of primary ovarian insufficiency after quadrivalent human papillomavirus (4HPV) vaccination.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study with follow-up from 2007 to 2016 used nationwide data for 996 300 Danish-born girls and women aged 11 to 34 years. Cox proportional hazards regression was used to estimate hazard ratios (HRs) of primary ovarian insufficiency diagnoses by 4HPV vaccination status with adjustment for age, calendar period, and a propensity score summarizing health care use. Data were analyzed from October 2020 to January 2021.
Receiving 4HPV vaccination compared with receiving no vaccination.
The main outcome was hospital contacts for primary ovarian insufficiency, and the main outcome measures were HRs comparing rates of primary ovarian insufficiency among vaccinated and unvaccinated individuals.
During 6 781 166 person-years of follow-up among 996 300 girls and women aged 11 to 34 years (505 829 vaccinated individuals [50.8%] and 490 471 unvaccinated individuals [49.2%]), 144 individuals were diagnosed with primary ovarian insufficiency, including 54 individuals diagnosed after 4HPV vaccination. The median (interquartile range) age of primary ovarian insufficiency diagnosis was 26.94 (12.68) years. The adjusted HR of primary ovarian insufficiency comparing 4HPV vaccination to no vaccination was 0.96 (95% CI, 0.55-1.68).
This study found no association between HPV vaccination and primary ovarian insufficiency. However, given the rarity of the outcome in this study, the presence of a clinically relevant increase in rate of diagnosis cannot be excluded.
轶事性病例报告提示人乳头瘤病毒（HPV）疫苗接种与原发性卵巢功能不全之间存在关联，但关于HPV与原发性卵巢功能不全的观察性研究较少，且研究结果并不支持两者存在关联。然而，现有研究受统计效力所限，在许多国家，对疫苗接种后不孕的担忧导致预防癌症疫苗的接种率较低。
评估四价人乳头瘤病毒（4HPV）疫苗接种后原发性卵巢功能不全的风险。
设计、设置和参与者：这项回顾性队列研究随访时间为2007年至2016年，使用了全国范围内996300名丹麦出生的11至34岁女孩和女性的数据。采用Cox比例风险回归分析，根据4HPV疫苗接种状况估计原发性卵巢功能不全诊断的风险比（HR），并对年龄、日历时间和总结医疗保健使用情况的倾向评分进行调整。数据于2020年10月至2021年1月进行分析。
接种4HPV疫苗与未接种疫苗。
主要结局是因原发性卵巢功能不全而就医，主要结局测量指标是比较接种疫苗者和未接种疫苗者原发性卵巢功能不全发生率的HR。
在996300名11至34岁女孩和女性（505829名接种疫苗者[50.8%]和490471名未接种疫苗者[49.2%]）的6781166人年随访期间，144人被诊断为原发性卵巢功能不全，其中54人在接种4HPV疫苗后被诊断。原发性卵巢功能不全诊断的中位（四分位间距）年龄为26.94（12.68）岁。比较接种4HPV疫苗与未接种疫苗的原发性卵巢功能不全调整后HR为0.96（95%CI，0.55-1.68）。
本研究未发现HPV疫苗接种与原发性卵巢功能不全之间存在关联。然而，鉴于本研究中该结局罕见，不能排除诊断率出现具有临床意义的增加。
