Fei Jing, Zhai Lingyun, Wang Jing, Zhu Xiaoqing, Liu Pei, Wang Linhai, Ma Dongxue, Li Lei, Zhou Jianwei
Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310003, China.
Department of Medical Laboratory, Beijing Origin-Poly Bio-Tec Co., Ltd., Beijing, 102629, China.
Clin Epigenetics. 2024 Dec 26;16(1):190. doi: 10.1186/s13148-024-01804-w.
Referring all women who tested positive for human papillomavirus (HPV) 16/18 to colposcopy may lead to potential over-referral issues. Triage tests based on cytology results face challenges in achieving accurate diagnoses. Our study aims to assess the clinical effectiveness of PAX1/JAM3 methylation (CISCER) test as a triage method for HPV 16/18-positive women.
From November 2021 to December 2022, a total of 334 women who tested positive for HPV 16/18 and were referred to colposcopy at The Second Affiliated Hospital of Zhejiang University School of Medicine were studied. The clinical utility of the CISCER test, cytology, and the combination of CISCER with cytology as potential triage tests was compared.
We observed a significant increase in the methylation levels of PAX1 gene and JAM3 gene in women with cervical intraepithelial neoplasia (CIN) grade 2 or severe (CIN2+). The CISCER test demonstrated superior triage performance over cytology, even when used in combination with cytology, showing a high sensitivity of 89.0% (95% confidence interval [CI] 82.9-95.1%) and specificity of 95.3% (95% CI 92.6-98.0%). It achieved an area under the curve of 0.921 (95% CI 0.877-0.966) and an odds ratio of 164.02 (95% CI 68.64-391.95). The immediate CIN2+ risk based on positive CISCER results would be 89.0% (95% CI 80.8-94.1%), with an estimated average of 1.12 referrals needed to detect one CIN2+ case. Moreover, CISCER triaging successfully identified all cancer patients and did not miss any CIN3+ cases among women aged ≥ 30.
The PAX1/JAM3 methylation detection exhibited excellent accuracy in identifying cervical precancerous lesions in HPV 16/18-positive women and could be considered as a triage tool to reduce excessive referrals for colposcopy and overtreatment.
将所有检测出人乳头瘤病毒（HPV）16/18呈阳性的女性转诊至阴道镜检查可能会导致潜在的过度转诊问题。基于细胞学结果的分流检测在实现准确诊断方面面临挑战。我们的研究旨在评估PAX1/JAM3甲基化（CISCER）检测作为HPV 16/18阳性女性分流方法的临床有效性。
2021年11月至2022年12月，对浙江大学医学院附属第二医院共334例HPV 16/18检测呈阳性并被转诊至阴道镜检查的女性进行了研究。比较了CISCER检测、细胞学检查以及CISCER与细胞学联合作为潜在分流检测的临床效用。
我们观察到宫颈上皮内瘤变（CIN）2级或更严重（CIN2+）女性中PAX1基因和JAM3基因的甲基化水平显著升高。CISCER检测在分流性能上优于细胞学检查，即使与细胞学联合使用时也是如此，显示出89.0%的高灵敏度（95%置信区间[CI]82.9 - 95.1%）和95.3%的特异性（95%CI 92.6 - 98.0%）。其曲线下面积为0.921（95%CI 0.877 - 0.966），优势比为164.02（95%CI 68.64 - 391.95）。基于CISCER阳性结果的即时CIN2+风险为89.0%（95%CI 80.8 - 94.1%），估计平均检测出1例CIN2+病例需要1.12次转诊。此外，CISCER分流成功识别了所有癌症患者，且在年龄≥30岁的女性中未遗漏任何CIN3+病例。
PAX1/JAM3甲基化检测在识别HPV 16/18阳性女性的宫颈癌前病变方面表现出优异的准确性，可被视为一种分流工具，以减少阴道镜检查的过度转诊和过度治疗。
