Quadrivalent HPV Vaccination and Risk of Multiple Sclerosis and Other Demyelinating Diseases of the Central Nervous System
Quadrivalent HPV Vaccination and Risk of Multiple Sclerosis and Other Demyelinating Diseases of the Central Nervous System
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DOI：
10.1001/jama.2014.16946
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发表时间：
2015-01-06
影响因子：
120.7
通讯作者：
Hviid, Anders
中科院分区：
文献类型：
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作者：
Scheller, Nikolai Madrid;Svanstrom, Henrik;Hviid, Anders
重要性病例报告提示人乳头瘤病毒（HPV）疫苗接种与多发性硬化和其他脱髓鞘疾病的发生之间存在联系。目的探讨四价HPV（qHPV）疫苗接种是否与多发性硬化和其他脱髓鞘疾病的风险增加相关。和参与者使用全国范围的登记，我们确定了一个队列的所有女性年龄在10岁至44岁的丹麦和瑞典，随访从2006年至2013年，关于qHPV疫苗接种的信息，以及关于多发性硬化症和其他脱髓鞘疾病的偶发性诊断的数据。主要分析采用队列设计，包括接种疫苗和未接种疫苗的研究参与者。次要分析采用自身对照病例系列设计，仅包括病例。两项分析均使用疫苗接种后2年的风险期。暴露有关qHPV疫苗接种的信息通过国家疫苗接种和处方登记册获得。主要结果和指标主要结果是多发性硬化症和其他脱髓鞘疾病的复合终点。使用泊松回归估计发病率比，比较接种疫苗后2年的风险期和未接种疫苗的时间periods.RESULTS的事件发生率的研究包括3 983 824名女性，其中789 082人接受了总的1 927 581 qHPV疫苗剂量。在随访期间，确定了4322例多发性硬化症和3300例其他脱髓鞘疾病，其中73例和90例分别发生在危险期内。在队列分析中，没有增加多发性硬化症的风险（接种和未接种阶段的粗发病率分别为6.12起事件/100 000人-年[95% CI，4.86-7.69]和21.54起事件/100 000人-年[95% CI，20.90-22.20];校正率比，0.90 [95% CI，0.70-1.15]）或其他脱髓鞘疾病（粗发生率，7.54起事件/10万人-年[95%CI，6.13-9.27]和16.14起事件/10万人-年[95%CI，15.58-16.71];校正率比，1.00 [95% CI，0.80-1.26]）。同样，使用自身对照病例系列设计也未发现风险增加（多发性硬化：发病率比，1.05 [95%CI，0.79-1.38];其他脱髓鞘疾病：发病率比，1.14 [95%CI，0.88-1.47]）。结论和相关性在这项覆盖2个斯堪的纳维亚国家的全国范围的研究中，qHPV疫苗接种与多发性硬化或其他脱髓鞘疾病的发生无关。这些发现并不支持qHPV疫苗接种与脱髓鞘疾病之间存在因果关系的担忧。
IMPORTANCE Case reports have suggested a link between human papillomavirus (HPV) vaccination and development of multiple sclerosis and other demyelinating diseases.OBJECTIVE To investigate if quadrivalent HPV (qHPV) vaccination is associated with an increased risk of multiple sclerosis and other demyelinating diseases.DESIGN, SETTING, AND PARTICIPANTS Using nationwide registers we identified a cohort of all females aged 10 years to 44 years in Denmark and Sweden, followed up from 2006 to 2013, information on qHPV vaccination, and data on incident diagnoses of multiple sclerosis and other demyelinating diseases. The primary analysis used a cohort design including vaccinated and unvaccinated study participants. A secondary analysis used a self-controlled case-series design including only cases. Both analyses used a 2-year risk period following vaccination.EXPOSURES Information on qHPV vaccination was obtained through the national vaccination and prescription registers.MAIN OUTCOMES AND MEASURES The primary outcomes were multiple sclerosis and a composite end point of other demyelinating diseases. Incidence rate ratios were estimated using Poisson regression, comparing rates of events in the 2-year risk periods following vaccination and in unvaccinated time periods.RESULTS The study included 3 983 824 females, among whom 789 082 received a total of 1 927 581 qHPV vaccine doses. During follow-up, 4322 multiple sclerosis cases and 3300 cases of other demyelinating diseases were identified, of which 73 and 90, respectively, occurred within the risk period. In the cohort analysis, there was no increased risk of multiple sclerosis (crude incidence rates, 6.12 events/100 000 person-years [95% CI, 4.86-7.69] and 21.54 events/100 000 person-years [95% CI, 20.90-22.20] for the vaccinated and unvaccinated periods; adjusted rate ratio, 0.90 [95% CI, 0.70-1.15]) or other demyelinating diseases (crude incidence rates, 7.54 events/100 000 person-years [95% CI, 6.13-9.27] and 16.14 events/100 000 person-years [95% CI, 15.58-16.71]; adjusted rate ratio, 1.00 [95% CI, 0.80-1.26]) associated with qHPV vaccination. Similarly, no increased risk was found using the self-controlled case-series design (multiple sclerosis: incidence ratio, 1.05 [95% CI, 0.79-1.38]; other demyelinating diseases: incidence ratio, 1.14 [95% CI, 0.88-1.47]).CONCLUSIONS AND RELEVANCE In this study with nationwide coverage of 2 Scandinavian countries, qHPV vaccination was not associated with the development of multiple sclerosis or other demyelinating diseases. These findings do not support concerns about a causal relationship between qHPV vaccination and demyelinating diseases.