健康女性接种人乳头状瘤病毒疫苗后不良反应发生情况分析

Analysis of adverse reactions in healthy females after vaccination with human papillomavirus vaccine

目的了解健康女性接种人乳头状瘤病毒(HPV)疫苗后不良反应发生情况。方法研究对象为2018年2月至2019年6月在首都医科大学附属北京友谊医院接种HPV四价(HPV4)疫苗和HPV九价(HPV9)疫苗的适龄健康女性。通过自行建立的HPV疫苗受种者信息登录系统,收集受种者的基本情况(年龄、身份、学历等)、疫苗接种情况、不良反应发生情况及转归情况进行回顾性分析,并比较不同疫苗和不同剂次疫苗接种后不良反应发生情况的差异。结果纳入分析的受种者共677人。接种首剂HPV4疫苗者510人,年龄(33±6)岁,其中467人接种了第2剂疫苗;接种首剂HPV9疫苗者167人,年龄(24±2)岁,其中118人接种了第2剂疫苗。677人中,身份为干部或职员者533人(78.7%),学生85人(12.6%),家庭主妇59人(8.7%);学历为本科及以上者525人(77.5%),本科以下者152人(22.5%)。接种HPV疫苗后出现的不良反应包括局部反应(注射部位疼痛、红肿及硬结)和全身反应(发热、恶心、乏力及月经周期紊乱)。接种首剂HPV4疫苗和首剂HPV9疫苗者总体不良反应发生率和局部不良反应发生率差异均有统计学意义[2.5%(13/510)比15.6%(26/167),χ2=39.283,P<0.001;1.6%(8/510)比12.6%(21/167),χ2=37.169,P<0.001],全身反应发生率差异无统计学意义[1.0%(5/510)比3.0%(5/167),χ2=3.505,P=0.061]。接种第2剂HPV4疫苗和第2剂HPV9疫苗者总体不良反应发生率、局部反应发生率和全身反应发生率差异均无统计学意义[1.3%(6/467)比2.5%(3/118),χ2=0.984,P=0.321;0.6%(3/467)比2.5%(3/118),χ2=3.350,P=0.067;0.6%(3/467)比0(0/118),χ2=0.762,P=0.383]。接种首剂与第2剂HPV4疫苗后局部不良反应和全身不良反应发生率的差异均无统计学意义[1.6%(8/510)比0.6%(3/467),χ2=1.879,P=0.171;1.0%(5/510)比0.6%(3/467),χ2=0.343,P=0.558];接种首剂与第2剂HPV9疫苗后局部不良反应发生率的差异有统计学意义[12.6%(21/167)比2.5%(3/118),χ2=9.024,P=0.003],全身不良反应发生率的差异无统计学意义[3.0%(5/167)比0(0/118),χ2=3.596,P=0.058]。接种后出现的局部或全身不良反应均不需治疗,可自行缓解。结论少数接种HPV4或HPV9疫苗的健康女性可发生不良反应,不良反应多较轻微,可自行缓解。2种HPV疫苗的不良反应主要出现在首剂接种后,接种首剂HPV9疫苗者不良反应发生率高于接种首剂HPV4疫苗者。

Objective To investigate the occurrence of adverse reactions in healthy females after vaccination with human papillomavirus(HPV)vaccine.Methods The subjects were healthy females of the right ages who were vaccinated with 4-valent HPV vaccine and 9-valent HPV vaccine in Beijing Friendship Hospital,Capital Medical University from February 2018 to June 2019.The basic information(age,identity,education,and etc.),vaccination,adverse reactions,and outcomes of HPV vaccine recipients were collected by the self-established HPV vaccine recipient information login system and analyzed retrospectively.The differences of adverse reactions of recipients with different vaccines and different times of vaccines were compared.Results A total of 677 recipients were enrolled in the analysis.Five hundred and ten reci-pients with an age of(33±6)years received the first dose of 4-valent HPV vaccine,and 467 of them received the second dose;167 recipients with an age of(24±2)years received the first dose of 9-valent HPV vaccine,and 118 of them received the second dose.Among the 677 recipients,533(78.7%)were cadres or office workers,85(12.6%)were students,and 59(8.7%)were housewives;525(77.5%)had bachelor degree or above and 152(22.5%)had below bachelor degree.The adverse reactions after HPV vaccination included injection site local reactions(including pain,swelling,and induration)and systemic reactions(including fever,nausea,fatigue,and menstrual cycle disorders).The differences in the incidences of overall and local adverse reactions after inoculations between the first dose of 4-valent HPV vaccine and the first dose of 9-valent HPV vaccine were statistically significant[2.5%(13/510)vs.15.6%(26/167),χ2=39.283,P<0.001;1.6%(8/510)vs.12.6%(21/167),χ2=37.169,P<0.001],but the difference in the incidence of systemic reactions was not statistically significant[1.0%(5/510)vs.3.0%(5/167),χ2=3.505,P=0.061].The differences in the incidences of overall adverse reactions,local reactions,and systemic reactions between the second doses of 4-valent HPV and 9-valent HPV vaccines were not statistically significant[1.3%(6/467)vs.2.5%(3/118),χ2=0.984,P=0.321;0.6%(3/467)vs.2.5%(3/118),χ2=3.350,P=0.067;0.6%(3/467)vs.0(0/118),χ2=0.762,P=0.383].The differences in the incidence of local and systemic adverse reactions between the first and the second dose of 4-valent HPV vaccine were not statistically significant[1.6%(8/510)vs.0.6%(3/467),χ2=1.879,P=0.171;1.0%(5/510)vs.0.6%(3/467),χ2=0.343,P=0.558].The difference in the incidence of local adverse reactions between the first dose and the second dose of 9-valent HPV vaccine was statistically significant[12.6%(21/167)vs.2.5%(3/118),χ2=9.024,P=0.003],and the difference in the incidence of systemic adverse reactions was not statistically significant[3.0%(5/167)vs.0(0/118),χ2=3.596,P=0.058].The local or systemic reactions after vaccination did not need treatment and could be self-relieving.Conclusions A few healthy females vaccinated with 4-valent or 9-valent HPV vaccines may have adverse reactions,most of which are mild and self-relieving.The adverse reactions of the 2 HPV vaccines mainly occur after the first dose of vaccination.The incidence of adverse reactions of the first dose of 9-valent HPV vaccine is higher than that of the first dose of 4-valent HPV vaccine.