Kong Linghua, Xiao Xiaoping, Wu Huanwen, You Yan, Jin Xitong, Liou Yuligh, Liu Pei, Lang Jinghe, Li Lei
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing 100730, People's Republic of China.
National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing 100730, People's Republic of China.
Oncologist. 2025 Mar 10;30(3). doi: 10.1093/oncolo/oyae324.
DNA methylation is a promising biomarker for cervical cancer screening. This study aimed to validate the triage performance of cytological DNA methylation for detecting cervical intraepithelial neoplasia of grade 3 or worse (CIN3+) in women with high-risk human papillomavirus (hrHPV) infection from a large prospective cohort undergoing opportunistic screening in China (METHY3).
The triage performance for detecting CIN3+ lesions was compared between HPV16/18 genotyping, a liquid-based cytology (LBC) test, and the PAX1 and JAM3 methylation (PAX1m/JAM3m) test according to cervical pathologic outcomes. Among the 4394 women infected with hrHPV, 1105 had definitive cervical histological findings that were analyzed.
For detecting CIN3+, the specificity of HPV16/18(+), the LBC result of ≥atypical squamous cells of undetermined significance (ASCUS), and PAX1m/JAM3m(+) was 66.4%, 23.9%, and 89.6%, respectively, with odds ratios of 4.24 (95% confidence interval [CI], 2.85-6.40), 4.44 (2.27-10.1), and 18.5 (12.1-28.7) (P < .001), respectively. PAX1m/JAM3m(+) had the highest area under the receiver operating characteristic curve (0.790, 95% CI, 0.747-0.832) in the whole cohort and in women of various ages. PAX1m/JAM3m (+) was detected in all patients with cancer (n = 28). Compared with HPV16/18 genotyping and the LBC test, PAX1m/JAM3m testing reduced referrals to colposcopy by 20.64 percentage points and 61.18 percentage points, respectively.
PAX1 m /JAM3 m testing is highly specific for detecting CIN3+. As a triage biomarker, it is superior to HPV 16/18 genotyping and LBC testing for women with hrHPV infection.
DNA甲基化是一种很有前景的宫颈癌筛查生物标志物。本研究旨在验证在中国进行机会性筛查的大型前瞻性队列中，高危型人乳头瘤病毒（hrHPV）感染女性的细胞学DNA甲基化检测高级别宫颈上皮内瘤变（CIN3+）的分流性能（METHY3）。
根据宫颈病理结果，比较HPV16/18基因分型、液基细胞学（LBC）检测和PAX1与JAM3甲基化（PAX1m/JAM3m）检测对CIN3+病变的分流性能。在4394例hrHPV感染女性中，1105例有明确的宫颈组织学检查结果并进行分析。
对于CIN3+检测，HPV16/18（+）、LBC结果为意义不明确的非典型鳞状细胞（ASCUS）及以上、PAX1m/JAM3m（+）的特异性分别为66.4%、23.9%和89.6%，优势比分别为4.24（95%置信区间[CI]，2.85-6.40）、4.44（2.27-10.1）和18.5（12.1-28.7）（P<0.001）。在整个队列及各年龄段女性中，PAX1m/JAM3m（+）在受试者工作特征曲线下面积最大（0.790，95%CI，0.747-0.832）。所有癌症患者（n=28）均检测到PAX1m/JAM3m（+）。与HPV16/18基因分型和LBC检测相比，PAX1m/JAM3m检测分别将阴道镜检查转诊率降低了20.64个百分点和61.18个百分点。
PAX1m/JAM3m检测对CIN3+检测具有高度特异性。作为一种分流生物标志物，对于hrHPV感染女性，它优于HPV16/18基因分型和LBC检测。
