比较脱氧核糖核酸甲基化分析与细胞学在妇科门诊人群中高危型人乳头瘤病毒阳性妇女中检测宫颈（前）癌的性能。

Comparing the performance of DeoxyriboNucleic Acid methylation analysis and cytology for detecting cervical (pre)cancer in women with high-risk human papillomavirus-positive status in a gynecologic outpatient population.

机构信息

Department of Medical Statistics, Hunan Hoomya Gene Technology Co., Ltd, Changsha, 410205, China.

Department of Obstetrics & Gynecology, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, China.

出版信息

BMC Cancer. 2024 Nov 4;24(1):1352. doi: 10.1186/s12885-024-13126-4.

DOI:10.1186/s12885-024-13126-4

PMID:39497123

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11536530/

Abstract

BACKGROUND

Primary screening for high-risk human papillomavirus (hrHPV) with cytological triage for women with non-16/18 hrHPV-positive status has become popular in China. However, cytology relies on the subjective judgment of pathologists, leading to inconsistent clinical performance.

METHODS

A total of 657 hrHPV-positive women aged 25-64 years were enrolled in this cross-sectional study. All participants underwent colposcopic biopsy after cytology triage, with cytology residual specimens undergoing DNA methylation testing. CIN2+ and CIN3+ sensitivity and specificity were compared between the different triage strategies (n=487): PAX1 methylation (PAX1) , Glycophorin C methylation (GYPC), cytology, and combinations between them or with HPV16/18.

RESULTS

The area under the receiver operating characteristic curves (AUCs) for PAX1 and GYPC in detecting CIN2 or worse (CIN2+) were 0.867 (95% confidence interval [CI]: 0.796-0.937) and 0.873 (95% CI: 0.808-0.938), respectively. The sensitivities of PAX1 and GYPC were consistent with those of cytology for both CIN2+ and CIN3+ detection. The relative specificities of PAX1 and GYPC for CIN2+ detection compared to cytology were 2.83 (95% CI: 2.33-2.45) and 3.09 (95% CI: 2.40-3.98), respectively. The relative specificities of combining HPV 16/18 with PAX1 and GYPC for CIN2+ detection compared to cytology were 3.38 (95% CI: 2.96-3.86) and 3.67 (95% CI: 3.15-4.27), respectively. Compared to low levels of DNA methylation, high levels of PAX1 and GYPC resulted in odd ratios (ORs) of 57.66 (95% CI: 13.57-409.12, p < 0.001) and 23.87 (95% CI: 6.49-115.42, p < 0.001) for CIN3+, adjusted for HPV 16/18 and cytology results.

CONCLUSIONS

PAX1 and GYPC demonstrated superior ability to identify cervical precancerous lesions and cervical cancer, with AUC values exceeding 0.85. For detecting CIN2+/CIN3+ in women with hrHPV-positive status, DNA methylation (combined with HPV 16/18) showed higher specificity than cytology (combined with HPV 16/18) and is a potential molecular biomarker for detecting cervical (pre)cancer.

摘要

背景

在中国，对非 16/18 高危型人乳头瘤病毒（hrHPV）阳性状态的女性进行 hrHPV 初筛联合细胞学分流已得到广泛应用。然而，细胞学依赖于病理学家的主观判断，导致其临床性能不一致。

方法

本横断面研究共纳入 657 名年龄在 25-64 岁之间的 hrHPV 阳性女性。所有参与者均在细胞学分流后行阴道镜活检，细胞学剩余标本行 DNA 甲基化检测。比较不同分流策略（n=487）之间的 CIN2+和 CIN3+的灵敏度和特异性：PAX1 甲基化（PAX1）、血型糖蛋白 C 甲基化（GYPC）、细胞学，以及它们之间或与 HPV16/18 的组合：

结果

PAX1 和 GYPC 检测 CIN2 或更高级别病变（CIN2+）的受试者工作特征曲线（ROC）下面积（AUC）分别为 0.867（95%置信区间 [CI]：0.796-0.937）和 0.873（95% CI：0.808-0.938）。PAX1 和 GYPC 的灵敏度与细胞学检测 CIN2+和 CIN3+的灵敏度一致。与细胞学相比，PAX1 和 GYPC 检测 CIN2+的相对特异性分别为 2.83（95% CI：2.33-2.45）和 3.09（95% CI：2.40-3.98）。与细胞学相比，HPV16/18 联合 PAX1 和 GYPC 检测 CIN2+的相对特异性分别为 3.38（95% CI：2.96-3.86）和 3.67（95% CI：3.15-4.27）。与低水平的 DNA 甲基化相比，高水平的 PAX1 和 GYPC 导致 CIN3+的比值比（OR）分别为 57.66（95% CI：13.57-409.12，p<0.001）和 23.87（95% CI：6.49-115.42，p<0.001），校正 HPV16/18 和细胞学结果后。