阴道微生态与高危型HPV阳性子宫颈鳞状上皮内病变的相关性及临床预测模型建立

Relationship between vaginal microecology and cervical squamous intraepithelial lesions in high-risk HPV positive women with and establishment of clinical prediction model

目的研究阴道微生态与高危型人乳头瘤病毒(human papillomavirus,HPV)阳性子宫颈鳞状上皮内病变(squamous intraepithelial lesion,SIL)的相关性,探讨阴道微生态对高危型HPV阳性SIL诊断预测的临床意义。方法选取2019年4月—2021年4月于同济大学附属第十人民医院妇科就诊的高危型HPV阳性,并经阴道镜检查、子宫颈组织活检或LEEP术明确宫颈病理结果的女性757例,根据组织病理结果将患者分为SIL组(n=347)及宫颈组织良性改变组(对照组,n=410)。回顾性分析入组患者临床资料及术前阴道微生态检测结果,比较SIL组与对照组之间阴道微生态的差异并建立阴道微生态与高危型HPV阳性SIL的诊断临床预测模型。结果与对照组相比,SIL组孕次增加,HPV16、18型感染率较高,阴道微生态失衡如阴道菌群多样性增加、乳酸杆菌功能下降、合并BV感染,差异均有统计学意义(P<0.05)。通过Logistic回归分析筛选出HPV阳性情况、菌群多样性、H_(2)O_(2)浓度、BV感染作为预测因子,纳入诊断临床预测模型并制作列线图。经过验证,模型的ROC曲线下面积为0.677;校准曲线显示预测概率与实际概率具有较好的一致性;临床决策曲线分析则显示该模型在一定范围内的临床实用度。结论本研究建立的诊断临床预测模型具有较好的区分度、校准度和临床实用度,有利于针对HPV阳性高风险发病患者观察随访及个体化治疗。

Objective To investigate the relationship between vaginal microecology and cervical squamous intraepithelial lesion(SIL)in high-risk human papillomavirus(HPV)positive women,and to establish a clinical prediction model of high-risk HPV positive SIL.Methods From April 2019 to April 2021,757 women with high-risk HPV positive were enrolled from the Department of Gynecology of Shanghai Tenth People's Hospital.According to the pathological results,there were 347 cases of cervical SIL(SIL group)and 410 cases of benign cervical tissue change(control group).The related clinical data and preoperative vaginal microecology test results were analyzed and compared between the SIL group and the control group.A clinical prediction model of high-risk HPV positive SIL was established and evaluated.Results Compared with the control group,the gravidity in SIL group increased,the infection rate of HPV type 16 and 18 was higher,and the imbalance of vaginal microecology was more distinct,including the increased vaginal flora diversity,the declined Lactobacillus function,and more bacterial vaginitis(BV)(P<0.05).Logistic regression analysis showed that positive HPV,bacterial diversity,H_(2)O_(2) concentration and BV infection were independent factors related to cervical SIL,based on which a clinical prediction model and nomogram were developed.The area under the ROC curve(AUC)of the model was 0.677;the calibration curve showed that the predicted probability was in good agreement with the actual probability;and the clinical decision curve analysis showed that the model had a certain range of clinical practicability.Conclusion The imbalance of vaginal microecology is related to the development of high-risk HPV positive SIL,especially HPV 16/18 positive SIL.The prediction model established in this study has good discrimination,calibration and clinical practicability,which is conducive to the follow-up and individualized treatment of high-risk HPV positive patients.