丹麦史坦顿血清研究所Anders Hviid团队分析了女性四价人乳头瘤病毒疫苗接种与自主神经功能障碍综合征之间的相关性。2020年9月2日，《英国医学杂志》发表了该成果。

为了评估四价人乳头瘤病毒疫苗接种与自主神经功能障碍综合征（如慢性疲劳综合征、复杂区域疼痛综合征和体位直立性心动过速综合征）之间的相关性，研究组进行了一项以人群为基础的自我控制病例系列研究。

研究组使用丹麦全国登记的ICD-10（国际疾病分类修订10版）诊断代码来确定人乳头瘤病毒疫苗接种和自主神经功能障碍信息，2007-2016年间，出生在丹麦的1375737名10-44岁的女性参与者中有869名患有自主神经功能障碍综合征。研究组比较了接种四价人乳头瘤病毒疫苗和未接种的女性参与者间经年龄和季节校正后的自主神经功能障碍综合征的发生率。

研究组共进行了10581902人年的随访，确定了869例具有自主神经功能障碍综合症的女性参与者，其中136例为慢性疲劳综合症，535例为复杂区域疼痛综合症，198例为体位直立性心动过速综合症。与未接种者相比，接种四价人乳头瘤病毒疫苗后在365天危险期内所有自主神经功能障碍综合征的发生率未显著增加，且风险期内慢性疲劳综合征、复杂区域疼痛综合征或体位直立性心动过速综合征等单独综合征的发生率亦未显著增加。

研究结果表明，与接种疫苗密切相关的不良事件可能纯粹是偶然发生的，四价人乳头瘤病毒疫苗接种与慢性疲劳综合征、复杂区域疼痛综合征或体位直立性心动过速综合征之间不存在因果关系。

附：英文原文

Title: Association between quadrivalent human papillomavirus vaccination and selected syndromes with autonomic dysfunction in Danish females: population based, self-controlled, case series analysis

Author: Anders Hviid, Nicklas M Thorsen, Palle Valentiner-Branth, Morten Frisch, Kre Mlbak

Issue&Volume: 2020/09/02

Abstract:

Objective To evaluate the association between quadrivalent human papillomavirus vaccination and syndromes with autonomic dysfunction, such as chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome.

Design Population-based self-controlled case series.

Setting Information on human papillomavirus vaccinations and selected syndromes with autonomic dysfunction (chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome) identified using ICD-10 (international classification of diseases, revision 10) diagnostic codes from Danish nationwide registers.

Participants 869 patients with autonomic dysfunction syndromes from a cohort of 1375737 Danish born female participants aged 10 to 44 years during 2007-16.

Main outcome measures Self-controlled case series rate ratios (95% confidence intervals) of the composite outcome of chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome, adjusted for age and season, comparing female participants vaccinated and unvaccinated with the quadrivalent human papillomavirus vaccine. Chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome were also considered separately in secondary analyses.

Results During 10581902 person years of follow-up, 869 female participants with syndromes of autonomic dysfunction (136 with chronic fatigue syndrome, 535 with complex regional pain syndrome, and 198 with postural orthostatic tachycardia syndrome) were identified. Quadrivalent human papillomavirus vaccination did not statistically significantly increase the rate of a composite outcome of all syndromes with autonomic dysfunction in a 365 day risk period following vaccination (rate ratio 0.99, 95% confidence interval 0.74 to 1.32) or the rate of any individual syndrome in the risk period (chronic fatigue syndrome (0.38, 0.13 to 1.09), complex regional pain syndrome (1.31, 0.91 to 1.90), or postural orthostatic tachycardia syndrome (0.86, 0.48 to 1.54)).

Conclusions When vaccination is introduced, adverse events could occur in close temporal relation to the vaccine purely by chance. These results do not support a causal association between quadrivalent human papillomavirus vaccination and chronic fatigue syndrome, complex regional pain syndrome, or postural orthostatic tachycardia syndrome, either individually or as a composite outcome. An increased risk of up to 32% cannot be formally excluded, but the statistical power of the study suggests that a larger increase in the rate of any syndrome associated with vaccination is unlikely.

DOI: 10.1136/bmj.m2930

Source: https://www.bmj.com/content/370/bmj.m2930