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阴道乳酸菌变化对高危型人乳头瘤病毒感染的宫颈上皮内瘤变发生的预测价值及列线图模型的构建与验证

Predictive value of vaginal lactic acid bacteria changes on occurrence of HR-HPV-infected cervical intraepithelial neoplasia and construction and validation of nomogram model.

作者信息

Huang Ying, Shen Yuliang, Wei Xuemei, Feng Jie, Zhu Lin

机构信息

Department of Obstetrics and gynecology reproductive center, The Ninth Medical Center of PLA General Hospital, Beijing, 100101, China.

Department of Obstetrics and gynecology reproductive center, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China.

出版信息

BMC Cancer. 2025 Jul 24;25(1):1212. doi: 10.1186/s12885-025-14604-z.

Abstract

OBJECTIVE

To explore the predictive value of vaginal lactic acid bacteria changes on the occurrence of HR-HPV infected cervical intraepithelial neoplasia (CIN), and to construct and validate Nomogram model.

METHODS

The community composition, quantitative distribution and other indicators of vaginal lactic acid bacteria in patients with and without CIN were detected and analyzed. The key lactic acid bacteria characteristics and other potential risk factors related to CIN were screened out using statistical methods, and then the Nomogram prediction model was constructed. The model discrimination was assessed by the receiver operating characteristic (ROC) and the calibration curves, and decision curves analysis (DCA) was performed to verify the reliability of the model.

RESULTS

There was no significant difference in the incidence of CIN, baseline data and vaginal lactic acid bacteria parameters between the training set and the verification set (P > 0.05). Univariate analysis identified significant differences in clinical factors (e.g., age of first sexual activity, safety measures) and vaginal lactobacilli (e.g., L. acidophilus, L. jenseni, L. gasseri, L. rhamnosus) between groups (P < 0.05). Multivariate Logistic regression confirmed safety measures, serum progesterone levels, and relative abundances of L. acidophilus, L. crispatus, L. jenseni, and L. rhamnosus as independent risk factors for CIN (P < 0.05). Further, the nomogram prediction model was constructed, and the nomogram model had good calibration and fit between prediction and reality in the training set and the verification set, and the nomogram demonstrated excellent discrimination in the training set and validation set, with calibration curves showing minimal absolute error (0.048 vs. 0.046) and DCA confirming clinical utility across a threshold probability of 0.05-0.95.

CONCLUSION

Changes in vaginal lactobacilli (e.g., reduced L. acidophilus, L. jenseni, L. gasseri, and L. rhamnosus) are significantly associated with CIN risk, potentially reflecting dysbiosis-driven vulnerability to HR-HPV persistence The Nomogram model demonstrated high accuracy in internal validation, suggesting its potential utility as a clinician-friendly tool for individualized risk assessment. However, external validation in prospective cohorts is required before clinical implementation.

摘要

目的

探讨阴道乳酸菌变化对高危型人乳头瘤病毒(HR-HPV)感染所致宫颈上皮内瘤变(CIN)发生的预测价值,并构建和验证列线图模型。

方法

检测并分析CIN患者和非CIN患者阴道乳酸菌的群落组成、定量分布等指标。采用统计学方法筛选出与CIN相关的关键乳酸菌特征及其他潜在危险因素,进而构建列线图预测模型。通过受试者工作特征曲线(ROC)和校准曲线评估模型的辨别力,并进行决策曲线分析(DCA)以验证模型的可靠性。

结果

训练集和验证集之间CIN发病率、基线数据及阴道乳酸菌参数无显著差异(P>0.05)。单因素分析发现,两组间临床因素(如初次性行为年龄、安全措施)和阴道乳酸杆菌(如嗜酸乳杆菌、詹氏乳杆菌、加氏乳杆菌、鼠李糖乳杆菌)存在显著差异(P<0.05)。多因素Logistic回归证实,安全措施、血清孕酮水平以及嗜酸乳杆菌、卷曲乳杆菌、詹氏乳杆菌和鼠李糖乳杆菌的相对丰度是CIN的独立危险因素(P<0.05)。此外,构建了列线图预测模型,该模型在训练集和验证集中具有良好的校准度,预测与实际情况拟合良好,且在训练集和验证集中具有出色的辨别力,校准曲线显示绝对误差极小(分别为0.048和0.046),DCA证实该模型在阈值概率为0.05-0.95时具有临床实用性。

结论

阴道乳酸杆菌的变化(如嗜酸乳杆菌、詹氏乳杆菌、加氏乳杆菌和鼠李糖乳杆菌减少)与CIN风险显著相关,可能反映了由生态失调导致的对HR-HPV持续感染的易感性。列线图模型在内部验证中显示出高准确性,表明其作为一种对临床医生友好的个体化风险评估工具具有潜在实用性。然而,在临床应用前需要在前瞻性队列中进行外部验证。

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