HPV16变异体对HSIL锥切术后持续感染及复发的影响

The influence of HPV16 variants on the persistent infection and recurrence after HSIL conization

目的:探索HPV16型E6、L1变异体对宫颈高度鳞状上皮内病变(HSIL)锥切术后持续感染及复发的预警作用。方法:选取2011年5月到2012年6月于上海市浦东新区人民医院HPV16型阳性、LEEP术后切缘阴性的HSIL患者100例,对其宫颈脱落细胞E6、L1基因测序,随访2年。持续感染及复发者再次测序明确HPV16变异体。结果:100例均检测出变异体,其中81.0%属亚洲原型(As.P),14.0%属欧洲变异体,2.0%属欧洲原型(EP),3.0%非洲1变异体(Af1)。欧洲变异体T350G、A442C有更高的HPV16持续感染及复发相关性(P<0.001)。94.0%的标本中出现L1基因变异H228D、T292A、449ins S,复发组、持续感染组与病毒清除组比较,差异无统计学意义(P>0.05)。结论:HPV16变异体与HSIL发生密切相关。上海浦东地区HPVl6导致的HSIL多属于亚洲型变异体,欧洲变异体E6 T350G/A442C可能有更高的锥切术后HPV16复发及持续感染相关性。L1基因变异可能不影响HSIL锥切术后HPV16病毒的复发及持续感染。

Objective： To investigate the early warning role of E6 and L1 variants of HPV16 on the persistent infection and recurrence after cervical HSIL（ High-grade squamous intraepithelial lesion） conization. Methods： 100 HSIL patients with HPV16 positive testing but negative incisal margin after LEEP（ loop electrosurgical excision procedure） among the women who visited the People＇s Hospital of Shanghai Pudong District during May 2011 to June 2012 were enrolled in this study.E6 and L1 genes of the cervical exfoliated cells of the patients were sequenced and the patients were followed up for two years. The above genes were sequenced once again to identify the HPV16 variants for the cases of persistent infection and recurrence.Results： HPVl6 variants were detected in all of the 100 patients,of which 81.0% belonged to the Asian prototype（ As.P）,14% belonged to the European variant,2% belonged to the European prototype（ EP）,3% belonged to the Africa 1 variant（ Af1）.It was found that HPV16 persistent infection and recurrence were more prone to arise for the European variants E6 T350 G,A442C（ P〈0.001）.In the vast majority of samples（ 94.0%）,L1 gene variants H228 D,T292A and 449 ins S appeared simultaneously,and the differences of L1 gene variants between the recurrence groups,persistent infection groups and viral clearance groups were not statistically significant（ P〈0.05）. Conclusions：（ 1） HPV16 variants were closely related to HSIL occurrence.（ 2） The HPV16 variants resulting in HSIL in Shanghai Pudong area belonged mostly to the Asian variants,（ 3） The European variants E6 T350 G,A442C may be more inclined to be associated with HPV16 persistent infection and recurrence after HSIL conization.（ 4） L1 gene variants don＇t seem to correlate with HPV16 persistent infection and recurrence after HSIL conization.