Department of Gynecology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.
Gynecological Oncology Research and Engineering Center of Hunan Province, 87 Xiangya Road, Changsha, 410008, Hunan, China.
Clin Epigenetics. 2024 Jun 7;16(1):77. doi: 10.1186/s13148-024-01691-1.
The major challenge in routine endocervical curettage (ECC) among Human Papillomavirus (HPV) 16/18-positive patients is that only a small fraction benefit. Nevertheless, current reported models often overestimate the validity and necessity of ECC, making it difficult to improve benefits for patients. This research hypothesized that assessing paired boxed gene 1 methylation levels (PAX1) and clinical characteristics could enhance the predictive accuracy of detecting additional high-grade squamous intraepithelial lesions or worse (HSIL +) through ECC that were not identified by colposcopy-directed biopsy (CDB).
Data from 134 women with HPV16/18 positivity undergoing CDB and ECC between April 2018 and April 2022 were collected and analyzed. Quantitative methylation-specific polymerase chain reaction (qMSP) was utilized to measure PAX1, expressed as ΔCp. Univariate and multivariate regression analyses were conducted to screen variables and select predictive factors. A nomogram was constructed using multivariate logistic regression to predict additional HSIL + detected by ECC. The discrimination, calibration, and clinical utility of the nomogram were evaluated using receiver operating characteristic curves (ROC) and the calibration plot.
Age (odds ratio [OR], 5.654; 95% confidence interval [CI], 1.131-37.700), cytology (OR, 24.978; 95% CI, 3.085-540.236), and PAX1 methylation levels by grade (PAX1 grade) (OR, 7.801; 95% CI, 1.548-44.828) were independent predictive factors for additional detection of HSIL + by ECC. In HPV16/18-positive women, the likelihood of additional detection of HSIL + through ECC increased with the severity of cytological abnormalities, peaking at 43.8% for high-grade cytological lesions. Moreover, when cytological findings indicated low-grade lesions, PAX1 methylation levels were positively correlated with the additional detection of HSIL + by ECC (P value < 0.001). A nomogram prediction model was developed (area under curve (AUC) = 0.946; 95% CI, 0.901-0.991), demonstrating high sensitivity (90.9%) and specificity (90.5%) at the optimal cutoff point of 107. Calibration analysis confirmed the model's strong agreement between predicted and observed probabilities.
The clinical nomogram presented promising predictive performance for the additional detection of HSIL + through ECC among women with HPV16/18 infection. PAX1 methylation level could serve as a valuable tool in guiding individualized clinical decisions regarding ECC for patients with HPV 16/18 infection, particularly in cases of low-grade cytological findings.
在 HPV16/18 阳性患者中进行常规宫颈管搔刮术（ECC）的主要挑战在于，只有一小部分患者受益。然而，目前报道的模型往往高估了 ECC 的有效性和必要性，使得难以提高患者的获益。本研究假设，通过评估配对盒基因 1 甲基化水平（PAX1）和临床特征，可以提高通过 ECC 检测未通过阴道镜引导活检（CDB）识别的额外高级别鳞状上皮内病变或更差病变（HSIL+）的预测准确性。
收集并分析了 2018 年 4 月至 2022 年 4 月期间 134 名 HPV16/18 阳性患者接受 CDB 和 ECC 的数据。采用定量甲基化特异性聚合酶链反应（qMSP）测量 PAX1，以 ΔCp 表示。采用单变量和多变量回归分析筛选变量并选择预测因素。采用多变量逻辑回归构建预测 ECC 检测到额外 HSIL+的列线图。采用受试者工作特征曲线（ROC）和校准图评估列线图的判别、校准和临床实用性。
年龄（比值比[OR]，5.654；95%置信区间[CI]，1.131-37.700）、细胞学（OR，24.978；95%CI，3.085-540.236）和 PAX1 甲基化水平（OR，7.801；95%CI，1.548-44.828）是 ECC 检测到额外 HSIL+的独立预测因素。在 HPV16/18 阳性女性中，随着细胞学异常严重程度的增加，通过 ECC 检测到额外 HSIL+的可能性增加，高级别细胞学病变时达到 43.8%。此外，当细胞学检查结果提示低级别病变时，PAX1 甲基化水平与 ECC 检测到额外 HSIL+呈正相关（P 值<0.001）。建立了列线图预测模型（曲线下面积（AUC）=0.946；95%CI，0.901-0.991），在最佳截断点为 107 时具有高敏感性（90.9%）和特异性（90.5%）。校准分析证实了该模型在预测概率与观察概率之间具有很强的一致性。
在 HPV16/18 感染女性中，该临床列线图在预测 ECC 检测到 HSIL+方面表现出良好的预测性能。PAX1 甲基化水平可作为 HPV16/18 感染患者进行 ECC 个体化临床决策的有价值工具，尤其是在细胞学检查结果为低级别时。
Zotero 插件
