Bao Heling, Zhang Xiaosong, Bi Hui, Zhao Yun, Fang Liwen, Wang Haijun, Wang Linhong
Department of Maternal and Child Health, Maternal and Child Health Department, School of Public Health, Peking University, Beijing, China.
National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Front Oncol. 2022 Jan 27;12:816789. doi: 10.3389/fonc.2022.816789. eCollection 2022.
This study aimed to explore the cluster patterns of cervical cancer screening strategies for detecting high-grade precancerous lesions in terms of benefits, costs, and efficiency.
A total of 2,065 referral women aged 25-64 years were recruited and underwent human papillomavirus (HPV) testing, liquid-based cytology with manual reading, and cytology with artificial intelligence (AI)-assisted reading. All women were assessed by colposcopy and histological examination. We formed 14 screening strategies based on primary cytology screening, primary HPV screening incorporating HPV-16/18 genotyping triage, cytology triage, or both, and co-testing. The primary outcomes were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+). The hierarchical clustering method was applied to multifaceted indicators, and then, the resulting clusters were described in terms of benefits, costs, efficiency, and their interaction. This study was registered (No. ChiCTR2000034131).
The relative sensitivity of HPV-based strategies compared with cytology alone with the threshold of LSIL+ ranged from 0.68 to 1.19 for CIN2+ detection and from 0.72 to 1.11 for CIN3+ detection, whereas the relative specificity ranged from 0.55 to 1.43 for CIN2+ detection and from 0.51 to 1.51 for CIN3+ detection. Five significant clusters according to the trade-off among benefits, costs, and efficiency were identified. The cluster including four primary HPV screening strategies showed the optimal balance. HPV testing with HPV-16/18 genotyping and AI-based cytology triage presented the optimal trade-off for CIN3+ detection relative to cytology alone in terms of relative sensitivity (1.06), relative specificity (0.72), colposcopies for 1 CIN3+ (3.7 vs. 3.1), a load of follow-up for women with HPV-positive and normal cytology (7.0% vs. 22.3%), and the work of manual cytology reading (35.1% vs. 100%).
Our study provided clinical and methodological evidence on the choice of HPV-based screening strategies. The cluster including primary HPV screening with genotyping and cytology triage showed an optimal balance among benefit, cost, and efficiency.
本研究旨在从效益、成本和效率方面探索宫颈癌筛查策略检测高级别癌前病变的聚类模式。
共招募2065名年龄在25至64岁之间的转诊女性，她们接受了人乳头瘤病毒（HPV）检测、手工阅片的液基细胞学检查以及人工智能（AI）辅助阅片的细胞学检查。所有女性均通过阴道镜检查和组织学检查进行评估。我们基于初次细胞学筛查、纳入HPV-16/18基因分型分流的初次HPV筛查、细胞学分流或两者兼有的联合检测，形成了14种筛查策略。主要结局为宫颈上皮内瘤变2级及以上（CIN2+）和3级及以上（CIN3+）。将层次聚类方法应用于多方面指标，然后根据效益、成本、效率及其相互作用对所得聚类进行描述。本研究已注册（编号：ChiCTR2000034131）。
以低度鳞状上皮内病变（LSIL）+为阈值，基于HPV的策略与单纯细胞学检查相比，检测CIN2+的相对灵敏度在0.68至1.19之间，检测CIN3+的相对灵敏度在0.72至1.11之间，而检测CIN2+的相对特异度在0.55至!1.43之间，检测CIN3+的相对特异度在0.51至1.51之间。根据效益、成本和效率之间的权衡，确定了5个显著聚类。包括4种初次HPV筛查策略的聚类显示出最佳平衡。在相对灵敏度（1.06）、相对特异度（0.72）、每例CIN3+的阴道镜检查次数（3.7比3.1）、HPV阳性且细胞学正常女性的随访负担（7.0%比22.3%）以及手工细胞学阅片工作量（35.1%比100%）方面，HPV-16/18基因分型检测与基于AI的细胞学分流相对于单纯细胞学检查，在检测CIN3+方面呈现出最佳权衡。
我们的研究为基于HPV的筛查策略选择提供了临床和方法学证据。包括基因分型初次HPV筛查和细胞学分流的聚类在效益、成本和效率之间显示出最佳平衡。
