CIN Ⅲ级患者阴道菌群改变及其与LEEP术后复发的关系分析

Vaginal flora changes in CIN Ⅲ patients and its relationship with recurrence after LEEP

摘要:

目的 探讨宫颈上皮内瘤变（CIN）Ⅲ级患者阴道菌群改变及其与宫颈环形电切术（LEEP）后复发的关系。方法 选取2016年3月至2020年8月于郑州市金水区总医院行LEEP治疗的432例CIN Ⅲ级患者为疾病组，另选取同期体检的健康女性420例为对照组，均收集阴道分泌物检测阴道菌群指标［菌群密集度、菌群多样性、霉菌、滴虫、乳酸杆菌、Nugent评分、pH值、白细胞酯酶（LE）、过氧化氢（H₂O₂）、唾液酸苷酶（SNA）、β-葡萄糖醛酸苷酶（GUS）、β-N-乙酰氨基葡萄糖苷酶（NAG）］，比较疾病组与对照组的阴道菌群指标。术后对疾病组患者进行两年随访，根据疾病组患者复发情况分为复发组和未复发组。比较术前及术后6个月时复发组和未复发组阴道菌群改变情况，采用多因素Logistic回归分析法分析CIN Ⅲ级患者LEEP术后复发的影响因素。结果 疾病组术前菌群密集度异常、菌群多样性异常、霉菌（+）、滴虫（+）、Nugent评分>7分、pH值>4.6、LE（+）、H₂O₂（+）、SNA（+）、GUS（+）占比均高于对照组（P<0.05），乳酸杆菌（+）占比低于对照组（P<0.05），两组NAG（+）占比比较差异无统计学意义（P>0.05）；LEEP术后对432例CIN Ⅲ级患者随访两年，复发率为9.49%；复发组与未复发组术前、术后6个月NAG（+）占比比较差异均无统计学意义（P>0.05），术后6个月菌群密集度异常、菌群多样性异常、霉菌（+）、滴虫（+）、Nugent评分>7分、pH值>4.6、LE（+）、H₂O₂（+）、SNA（+）、GUS（+）占比均低于术前（P<0.05），乳酸杆菌（+）占比高于术前（P<0.05）；术后6个月复发组菌群密集度异常、菌群多样性异常、Nugent评分>7分、pH值>4.6、LE（+）、SNA（+）、GUS（+）占比均高于未复发组（P<0.05），乳酸杆菌（+）占比低于未复发组（P<0.05）；经Logistic回归分析，术后6个月的菌群密集度异常、菌群多样性异常、Nugent评分>7分、pH值>4.6、LE（+）、SNA（+）、GUS（+）、绝经、术前高危型人乳头瘤病毒（HR-HPV）载量高负荷、累及腺体、手术切缘阳性均为影响CIN Ⅲ级患者LEEP术后复发的危险因素（P<0.05），乳酸杆菌（+）为其保护因素（P<0.05）。结论 阴道微生态菌群失衡与CIN Ⅲ级患者LEEP术后复发关系密切，此外，绝经、术前HR-HPV载量高负荷、累及腺体、手术切缘阳性均为影响CIN Ⅲ级患者LEEP术后复发的危险因素，临床可根据上述因素进行针对性管理，以降低CIN复发的风险。

Abstract:

Objective To investigate the changes of vaginal flora in patients with cervical intraepithelial neoplasia (CIN) Ⅲ and its relationship with recurrence after loop electrosurgical excision procedure (LEEP).Methods Totally 432 patients with CIN Ⅲ who underwent LEEP in our hospital from March 2016 to August 2020 were selected as the disease group, and 420 healthy women who underwent physical examination in the same period were selected as the control group. Collecting vaginal secretions to detect vaginal flora indicators [flora density, flora diversity, mold, trichomonas, lactobacillus, Nugent score, pH value, leukocyte esterase (LE), hydrogen peroxide (H₂O₂), sialidase (SNA), β-glucuronidase (GUS), β-N-acetylglucosaminidase (NAG)], and the vaginal flora indicators between the disease group and the control group were compared. The patients in the disease group were followed up for 2 years after operation, and they were divided into recurrence group and non-recurrence group according to the recurrence of the patients in the disease group. The changes of vaginal flora in the recurrence group and the non-recurrence group before operation and 6 months after operation were compared. Multivariate logistic regression analysis was used to analyze the influencing factors of recurrence after LEEP in patients with CIN Ⅲ.Results The proportions of abnormal flora density, abnormal flora diversity, mold (+), trichomonas (+), Nugent score >7 points, pH value >4.6, LE (+), H₂O₂ (+), SNA (+), GUS (+) in the disease group before operation were higher than those in the control group (P<0.05), and the proportion of lactobacillus (+) was lower than that in the control group (P<0.05), but there was no significant difference in the proportion of NAG (+) between the two groups (P>0.05). A total of 432 patients with CIN Ⅲ were followed up for 2 years after LEEP, and the recurrence rate was 9.49%. There was no significant difference in the proportion of NAG (+) between the recurrence group and the non-recurrence group before operation and 6 months after operation (P>0.05). The proportions of abnormal flora density, abnormal flora diversity, mold (+), trichomonad (+), Nugent score >7 points, pH value >4.6, LE (+), H₂O₂ (+), SNA (+) and GUS (+) in the recurrent group and the non-recurrent group at 6 months after operation were lower than those before operation (P<0.05), and the proportion of lactobacillus (+) was higher than that before operation (P<0.05). At 6 months after operation, the proportions of abnormal flora density, abnormal flora diversity, Nugent score >7 points, pH value >4.6, LE (+), SNA (+) and GUS (+) in the recurrence group were higher than those in the non-recurrence group (P<0.05), and the proportion of lactobacillus (+) was lower than that in the non-recurrence group (P<0.05). Logistic regression analysis showed that abnormal flora density, abnormal flora diversity, Nugent score >7 points, pH value >4.6, LE (+), SNA (+), GUS (+) at 6 months after operation and menopause, high load of preoperative high-risk human papillomavirus (HR-HPV), involvement of glands and positive surgical margin were all risk factors for recurrence of CIN Ⅲ patients after LEEP (P<0.05), while lactobacillus (+) was the protective factor for it (P<0.05).Conclusion The imbalance of vaginal microbiota is closely related to the recurrence after LEEP in CIN Ⅲ patients. In addition, menopause, high load of preoperative HR-HPV, involvement of glands and positive surgical margin are all risk factors affecting the recurrence of LEEP in CIN Ⅲ patients. Clinical management can be targeted according to the above factors to reduce the risk of recurrence of CIN.