HR-HPV感染合并CIN与阴道微环境、TAP1及TAP2基因多态性的关系研究

Relationship between high-risk HPV infection combined with cervical intraepithelial neoplasia and vaginal microenvironment and TAP1 and TAP2 gene polymorphisms

目的探讨高危型人乳头瘤病毒(HR-HPV)感染合并宫颈上颈上皮内瘤变(CIN)与阴道微环境、TAP1及TAP2基因多态的关系。方法收集2022年5月至2024年5月宁波大学附属第一医院收治的HR-HPV感染患者120例,行液基薄层细胞学检测或宫颈活检,合并CIN 75例(HR-HPV感染合并CIN组),不合并CIN 45例(HR-HPV感染组)。采集宫颈阴道分泌物,运用16S rRNA技术进行测序,比对Greengene数据库,以“门、属”水平分析两组阴道微环境菌群分布;收集外周静脉血行聚合酶链式反应扩增TAP1及TAP2基因多态性片段,分析HR-HPV感染合并CIN与TAP1、TAP2基因多态性的关系。结果“门”水平上,HRHPV感染合并CIN组厚壁菌门相对丰度低于HR-HPV感染组,放线菌门、拟杆菌门、变形菌门、软壁菌门及梭杆菌门均高于HR-HPV感染组(均P<0.05);“属”水平上,HR-HPV感染合并CIN组乳酸杆菌属低于HR-HPV感染组,加德纳菌属、普氏菌属、奇异菌属、脲原体属、纤毛菌属、链球菌属及厌氧球菌属均高于HRHPV感染组(均P<0.05)。两组TAP1、TAP2基因多态性位点理论值与实际值差异均无统计学意义(均P>0.05);两组TAP1 rs41549617位点基因型分布差异有统计学意义(P<0.05),且HR-HPV感染合并CIN组AA基因型、A等位基因频率高于HR-HPV感染组(均P<0.05);两组TAP2 rs1135216位点基因型分布差异无统计学意义(P>0.05)。结论HR-HPV感染患者可因阴道微生物菌群变化以及TAP1 rs41549617位点改变进一步发展为CIN,检测阴道微生物菌群以及TAP1 rs41549617位点有助于对HR-HPV感染患者进行风险分层,以便制定个体化随访策略。

Objective To investigate the relationship between high-risk human papilloma virus(HR-HPV)infection and cervial intraepithelial neoplasia(CIN)with vaginal microenvironment,TAP1,and TAP2 gene polymorphisms.Methods A total of one-hundred and twenty patients with HR-HPV infection were selected,thinprep liquibased cytology test(TCT)showed that sventy-five patients were complicated with CIN(HR-HPV infection combined with CIN group),and the other fourty-five patients were included in HR-HPV infection cervicitis group.Cervical and vaginal secretions were collected and sequenced by 16S r RNA technology.The distribution of vaginal microenvironment flora in the two groups was analyzed at the“phylum”and“genus”level by comparison with the Greengene database.TAP1 and TAP2 gene polymorphisms were amplified by polymerase chain reaction(PCR)in peripheral venous blood,and the relationship between CIN,TAP1 and TAP2 gene polymorphisms in HR-HPV infection was analyzed.Results At the“phylum”level,the relative abundance of Firmicutes in the HR-HPV infection complicated CIN group was lower than that in the HR-HPV infection cervicitis group,Actinobacteria,Bacteroidetes,Proteobacteria,Tenericutes and Fusobacteria were higher than those in HR-HPV infected cervicitis group(all P<0.05).At the“genus”level,the Lactobacillus in the HR-HPV infected CIN group was lower than that in the HR-HPV infected cervicitis group;Gardnerella,Prevotella,Atopobium,Ureaplasma,Sneathia,Streptococcus and Anaerococcus were higher than those in HR-HPV infected cervicitis group(all P<0.05).There was no significant difference between the theoretical and actual values of TAP1 and TAP2 polymorphic loci between the two groups(P>0.05).The genotype distribution of TAP1 rs41549617 locus was statistically significant between the two groups(P<0.05),and the AA genotype and A allele frequencies in the HR-HPV infection combined with CIN group were higher than those in the HR-HPV infection cervicitis group(all P<0.05).There was no significant difference in genotype distribution of TAP2 rs1135216between the two groups(P>0.05).Conclusions HR-HPV infected patients can further develop CIN due to changes in vaginal microflora and TAP1 rs41549617 site.Detection of vaginal microflora and TAP1 rs41549617 site is helpful for risk stratification of HR-HPV infected patients.