宫颈微生态对高级别宫颈上皮内瘤变患者锥切术后转归的影响分析

Association of cervical microecology with conization outcome of patients with high-grade squamous intraepithelial lesions

  • 摘要:
      背景  高级别宫颈上皮内瘤变(high-grade squamous intraepithelial lesions,HSIL)患者行宫颈锥切术,术后持续高危人乳头瘤病毒(high risk-human papilloma virus,HR-HPV)感染是进展为宫颈癌的主要因素,但导致持续感染的原因不详,需要进一步明确。
      目的  比较HSIL锥切术前宫颈微生态与术后转归的相关性,寻找导致术后持续感染的原因。
      方法  选取解放军总医院第一医学中心2020年9月- 2021年9月因HSIL行宫颈锥切术的病例,术前采集宫颈分泌物,根据术后3个月复查HR-HPV结果分为HR-HPV转阴组和HR-HPV阳性组,同时选取24例健康者作为对照组。进行核酸提取,针对16S rRNA的V3 + V4区域进行PCR扩增和测序,对有效数据进行分析,主要采用α、β多样性分析比较术前宫颈微生态差异。
      结果  通过倾向性匹配每组纳入24例,共72例。总体上宫颈微生物在属水平上以乳杆菌种为主。α多样性显示阳性组菌群多样性高于转阴组(P=0.039),转阴组宫颈群落多样性高于对照组(P=0.037),β多样性分析术后阳性组与转阴组较为相似,与对照组差异较大,优势菌群均为厚壁菌门(Firmcutes)。MetaStat综合分析三组数据,其中差异有统计学意义的菌属中丰度最高的为链球菌属(P=0.044)。
      结论  三组宫颈群落属水平均以乳杆菌属为优势菌;消化链球菌可能是影响锥切术后HR-HPV转归的重要因素;HSIL疾病本身及术后转归均与宫颈微生态密切相关。

     

    Abstract:
      Background  Persistent high-risk human papillomavirus (HR-HPV) infection after cervical conization is the main factor in the progression of high-grade squamous intraepithelial lesions (HSIL) to cervical cancer, but the cause of persistent infection is unknown and needs to be further clarified.
      Objective  To analyze the correlation between preoperative cervical microecology and postoperative outcome, so as to find out the cause of postoperative persistent infection after cervical conization.
      Methods  The patients who underwent cervical conization for HSIL in the First Medical Center of Chinese PLA General Hospital from September 2020 to September 2021 were enrolled according to the inclusion and exclusion criteria. The clinical data and cervical secretions before conization were collected. According to the results of HR-HPV test at 3 months after conization, the patients were divided into three groups (HR-HPV negative group, persistent infection group and healthy HPV-negative control group), with 24 patients in each group. Nucleic acid extraction was performed at the same time, PCR amplification and sequencing were performed for V3 + V4 region of 16S rRNA. Effective data were analyzed, mainly by α and β diversity analysis, to compare the preoperative cervical microecological differences.
      Results  The abundance of cervical community was mainly lactobacillus at species level. α diversity showed that the bacterial community diversity in the persistent infection group was higher than that in the negative transition group (P=0.039), and that in the negative transition group was higher than that in the control group (P=0.037). β diversity analysis showed that the persistent infection group was similar to the HR-HPV negative transition group, the dominant bacteria were Firmcutes, which showed a difference with the control group. In the comprehensive analysis (MetaStat) of the three groups of data, streptococcus had the highest abundance among the bacteria with statistically significant differences (P=0.044).
      Conclusion  Lactobacillus is the dominant bacterium in the three groups at species level. Digestive streptococcus may be an important factor affecting the outcome of HPV after conization. HSIL and the postoperative outcome are closely related to the cervical microecology.

     

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