目的:人乳头瘤病毒(HPV)16/18阳性患者常规宫颈刮宫(ECC)的主要挑战是仅有一小部分获益。然而,目前报道的模型往往高估了ECC的有效性和必要性,很难提高患者的获益。这项研究假设评估配对的盒装基因1甲基化水平(PAX1m)和临床特征可以提高通过ECC检测其他高级别鳞状上皮内病变或更差的病变(HSIL)的预测准确性,这些病变未通过阴道镜导向活检(CDB)。
方法:收集并分析了2018年4月至2022年4月期间接受CDB和ECC的134名HPV16/18阳性女性的数据。定量甲基化特异性聚合酶链反应(qMSP)用于测量PAX1m,表示为ΔCp。进行单因素和多元回归分析以筛选变量并选择预测因素。使用多变量逻辑回归构建列线图以预测ECC检测到的额外HSIL+。歧视,校准,使用受试者工作特征曲线(ROC)和校准图评估列线图的临床实用性。
结果:年龄(赔率比[OR],5.654;95%置信区间[CI],1.131-37.700),细胞学(或,24.978;95%CI,3.085-540.236),和PAX1甲基化水平(PAX1m等级)(OR,7.801;95%CI,1.548-44.828)是ECC额外检测HSIL+的独立预测因素。在HPV16/18阳性妇女中,通过ECC额外检测HSIL+的可能性随着细胞学异常的严重程度而增加,高级细胞学病变的峰值为43.8%。此外,当细胞学发现表明低度病变时,PAX1甲基化水平与ECC对HSIL+的额外检测呈正相关(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),在最佳截止点107显示高灵敏度(90.9%)和特异性(90.5%)。校准分析证实了模型在预测和观察到的概率之间的强烈一致性。
结论:临床列线图为HPV16/18感染女性通过ECC额外检测HSIL+提供了有希望的预测性能。PAX1甲基化水平可以作为指导HPV16/18感染患者ECC个体化临床决策的有价值的工具。特别是在低度细胞学发现的情况下。
OBJECTIVE: 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 (PAX1m) 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).
METHODS: 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 PAX1m, 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.
RESULTS: 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 (PAX1m 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.
CONCLUSIONS: 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.