HPV感染及高级别CIN患者阴道微生态研究

目的分析人乳头瘤病毒16、18(HPV16、18)宫颈感染及高级别宫颈上皮内瘤变(CIN)患者阴道微生态特征。方法以3例湿疣样变或CIN1级HPV16和/或18感染患者为低级别CIN组,以5例高级别CIN病变HPV16和/或18感染患者为高级别CIN组,以3例HPV阴性阴道炎患者为对照组,采用16S rRNA基因扩增技术分析各研究组患者阴道微生物菌群组成,采用分层聚类法分析并比较各研究组阴道微生物菌群分布特征。结果高级别CIN组阴道微生物细菌种类多样性及复杂性较低级别CIN组、对照组更为明显;从对照组、低级别CIN组至高级别CIN组,卷曲乳杆菌和穹隆乳杆菌丰度呈下降趋势,惰性乳杆菌丰度呈增加趋势;定植菌犬布鲁氏菌丰度呈下降趋势,致病菌戴阿李斯特琥珀酸纤毛杆菌、阴道加德纳菌和短普雷沃菌丰度呈上升趋势。结论高级别CIN患者阴道菌种结构复杂性、多样性明显。阴道乳杆菌种类和丰度对阴道健康起重要作用,惰性乳杆菌则具有相反作用。犬布鲁氏菌、戴阿李斯特琥珀酸纤毛杆菌、阴道加德纳菌和短普雷沃菌长期存在于阴道,与HPV持续感染、进展至高级别CIN病变密切相关。

Vaginal microbiome characterization in women with HPV16/18 infections and high-grade CIN

Objective To investigate the vaginal microbilme characterization in women with human papillomavirus(HPV)16 and 18 infection and high-grade cervical intraepithelial neoplasia(CIN).Methods Three groups were set,including control group(without HPV infection and with colpitis),low-grade CIN group(with HPV 16 or/and 18 infection),and high-grade CIN group(with HPV 16 or/and 18 infection).Virginal microbial composition was determined by using 16S rRNA amplication sequencing and hierarchical clustering analysis among three groups was applied.Rank sum test was used to determine statistical significance.Results Diversity and complexity of bacteria was significantly elevated in high-grade group.Compared with the control,the growth of Lactobacillus crispatus(L.crispatus) and Lactobacillus casei(L.casei) was significantly decreased,while Lactobacillus iners(L.iners) was significantly increased in low-grade CIN group and high-grade CIN group,and both were proportionally correlated to the grade of the disease.Brucella canis(B.canis),as colonized bacteria,was significantly decreased in both low-grade and high-grade CIN groups,and the changes were proportional to the grade of disease.The growth of Dialistersuccinatiphilus(D.succinatiphilus),Gardnerella vaginalis(G.vaginalis) and Prevotellabivia(P.bivia) were significantly elevated and proportional to the grade of disease.Conclusion The diversity and complexity of virginal microbial composition could be significantly expanded in women with HPV infection and high-grade CIN.In contrast to the important role of lactobacillus in virginal health,L.inners could be pathogenic.The colonization of B.canis,D.succinatiphilus,G.vaginalis and P.bivia might be highly correlated with HPV chronic infection and further development of CIN.