Objective: To evaluate the 10-year protective effect and immunogenicity of quadrivalent human papillomavirus (HPV) vaccine in Chinese women aged 20 to 45 years. Methods: From October 2019 to April 2020, a long-term follow-up study was conducted on the subjects of the Phase III clinical trial of the quadrivalent HPV vaccine (NCT00834106). Participants underwent a questionnaire survey, venous blood sampling, gynecological examination, cervical exfoliated cell pathology examination, and serum neutralizing antibody titers for HPV-6, 11, 16, and 18 were measured using a pseudovirus neutralization assay. The results of the cytological examination and the positive rate and titers of serum antibodies of different cervical exfoliated cells were compared. Results: A total of 889 subjects were followed up, including 240 in the control group, 453 in the vaccination group and 196 in the post-trial vaccination group. The age of the control group was (40±7) years old, which was higher than that of the supplementary vaccination group and the vaccination group [(38±4) and (38±6) years old, respectively] (P<0.05). There were no statistically significant differences in condom use and sexual frequency among all groups (all P values>0.05). The abnormal proportion of cervical exfoliation cytopathology in the vaccination group was 3.7% (17/453), which was significantly lower than that in the control group [9.6% (23/240)] and post-trial vaccination group [5.6% (11/196)] (P<0.05). There were two cases of cervical intraepithelial neoplasia (CIN) grade 1 in the vaccination group, two cases of CIN grade 1 and three cases of CIN grade 2 and above in the control group, and no CIN grade 1 and above cases in the post-trial vaccination group. The positive rate of HPV-18 antibody was 35.5% (161/453) in the vaccination group and 76.0% (149/196) in the post-trial vaccination group, which was significantly lower than that of other types (P<0.05). The neutralizing antibody GMT ratio between the vaccination group and the control group ranged from 2.62 to 25.33 (9.05 to 83.08). Conclusion: Protective neutralizing antibodies are sustained in Chinese women aged 20 to 45 years after ten years of vaccination with quadrivalent HPV vaccine.
目的： 评估20~45岁中国女性接种四价人乳头瘤病毒（HPV）疫苗10年保护效果和免疫原性。 方法： 于2019年10月至2020年4月对四价HPV疫苗Ⅲ期临床试验（NCT00834106）对象展开长期随访研究，进行问卷调查、静脉血采样、妇科检查、宫颈脱落细胞病理学检查并通过假病毒中和试验测定受试者血清HPV-6、11、16和18中和抗体滴度。比较不同对象宫颈脱落细胞的细胞学检查结果和血清抗体阳性率及滴度。 结果： 共随访889名对象，对照组、疫苗接种组和补接种组分别为240、453和196名。对照组年龄为（40±7）岁，高于补接种组和疫苗接种组［分别为（38±4）和（38±6）岁］（P<0.05），各组对象安全套使用情况和性生活频率差异均无统计学意义（均P>0.05）。接种组宫颈脱落细胞病理学检查异常比例为 3.7%（17/453），明显低于对照组［9.6%（23/240）］和补接种组［5.6%（11/196）］（P<0.05）。疫苗接种组子宫颈上皮内瘤变（CIN）1级2例，对照组CIN1级2例，CIN2级及以上3例，补接种组未发现CIN1级及以上病例。疫苗接种组和补接种组HPV-18抗体阳性率分别为35.5%（161/453）和76.0%（149/196），明显低于其他型别（P<0.05）。疫苗接种组（补接种组）与对照组中和抗体GMT比值范围为2.62~25.33（9.05~83.08）。 结论： 中国20~45岁女性接种四价HPV疫苗10年后仍存在保护性中和抗体。.