Zhao Fang-Hui, Zhang Wen-Hua, Pan Qin-Jing, Zhang Xun, Chen Wen, Liu Bin, Ma Jun-Fei, Hu Shang-Ying, Qiao You-Lin
Department of Cancer Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Zhonghua Zhong Liu Za Zhi. 2010 Jun;32(6):420-4.
To assess the feasibility and accuracy of different cervical cancer screening algorithms suitable for different regions, and promote the prevention and control of cervical cancer in China.
Using the data of a cross-sectional comparative trial of multiple techniques to detect cervical intraepithelial neoplasia in Xiangyuan County, Shanxi Province, conducted in 1999, to evaluate the feasibility and accuracy of different cervical cancer screening algorithms. All the women were screened by six screening tests, including liquid based cytology (LBC), fluorescence spectroscopy, visual inspection with 5% acetic acid staining (VIA), colposcopy, self-sampled HPV DNA and clinician-sampled HPV DNA test, and each woman had histopathological diagnosis. Different screening algorithms were developed by combining the screening tests in parallel or in serial, and the performance indexes of the algorithms such as sensitivity, specificity, colposcopy referral rate and receiver operating characteristic (ROC) curve for detecting the high grade lesions (>or= CIN 2) were compared.
Among the algorithms combined by LBC and HPV DNA testing, for the combination in parallel (either cytology was greater than ASC-US or HPV positives), its sensitivity was 100%, specificity was 68.6%, and colposcopy referral rate was 34.4%; for the algorithm of LBC as primary screening test, with ASC-US women triage by HPV DNA testing, its sensitivity was 93.0%, specificity was 89.9%, and colposcopy referral rate was 13.7%; for the algorithm of HPV DNA testing as the primary screening test, with HPV positive women triage by LBC, its sensitivity was 91.7%, specificity was 93.0%, and colposcopy referral rate was 10.6%. ROC analysis showed that LBC primary testing followed by HPV triage and HPV primary testing followed by LBC triage were much better than the combination in parallel (P = 0.0003, P = 0.0002). Among the algorithms with LBC or HPV DNA testing solely as primary screening test, the sensitivity, specificity and colposcopy referral rate of LBC were 94.2%, 77.3%, 25.7% and 87.2%, 93.5%, 10.0%, respectively, for cutoff by ASC-US or by LSIL; the sensitivity, specificity and colposcopy referral rate of HPV DNA testing were 97.6%, 84.8%, 18.8% and 83.5%, 85.9%, 17.1%, respectively, for clinician-sampled and self-sampled. Clinician-sampled HPV DNA testing was better than LBC cutoff by ASC-US or self-sampled HPV DNA testing (P = 0.005, P = 0.002). Among the algorithms combined by VIA and HPV DNA testing, the sensitivity, specificity and colposcopy referral rate were 70.9%, 74.3% and 27.6% for VIA alone as primary screening test; the sensitivity, specificity and colposcopy referral rate were 65.9%, 95.2% and 7.4% for HPV as primary screening test with HPV positive women triage by VIA. HPV primary testing followed by VIA triage was better than VIA alone (P = 0.004).
Considering the health-resource settings and women's preference, both HPV primary testing followed by LBC triage and LBC primary testing followed by HPV triage are suitable for developed regions, moderately developed regions may choose either LBC or HPV as the screening approach, VIA is a suitable primary screening test in less developed regions, and HPV primary testing followed by VIA triage will be more effective if low cost HPV test is available in the future.
评估适用于不同地区的不同宫颈癌筛查算法的可行性和准确性，推动中国宫颈癌的防治工作。
利用1999年在山西省襄垣县进行的一项采用多种技术检测宫颈上皮内瘤变的横断面比较试验的数据，评估不同宫颈癌筛查算法的可行性和准确性。所有女性均接受了六项筛查检测，包括液基细胞学检查（LBC）、荧光光谱检查、5%醋酸染色肉眼检查（VIA）、阴道镜检查、自我采样HPV DNA检测和临床医生采样HPV DNA检测，且每位女性均有组织病理学诊断。通过将筛查检测并行或串联组合，开发出不同的筛查算法，并比较这些算法在检测高级别病变（≥CIN 2）时的性能指标，如敏感性、特异性、阴道镜转诊率和受试者操作特征（ROC）曲线。
在LBC和HPV DNA检测组合的算法中，对于并行组合（细胞学结果大于ASC-US或HPV阳性），其敏感性为100%，特异性为68.6%，阴道镜转诊率为34.4%；对于以LBC作为初筛检测，ASC-US女性通过HPV DNA检测进行分流的算法，其敏感性为93.0%，特异性为89.9%，阴道镜转诊率为13.7%；对于以HPV DNA检测作为初筛检测，HPV阳性女性通过LBC进行分流的算法，其敏感性为91.7%，特异性为93.0%，阴道镜转诊率为10.6%。ROC分析表明，LBC初筛后HPV分流和HPV初筛后LBC分流比并行组合要好得多（P = 0.0003，P = 0.0002）。在仅以LBC或HPV DNA检测作为初筛检测的算法中，LBC以ASC-US或LSIL为截断值时，其敏感性、特异性和阴道镜转诊率分别为94.2%、77.3%、25.7%和87.2%、93.5%、10.0%；HPV DNA检测中，临床医生采样和自我采样时，其敏感性、特异性和阴道镜转诊率分别为97.6%、84.8%、18.8%和83.5%、85.9%、17.1%。临床医生采样的HPV DNA检测优于以ASC-US为截断值的LBC或自我采样的HPV DNA检测（P = 0.005，P = 0.002）。在VIA和HPV DNA检测组合的算法中，单独以VIA作为初筛检测时，其敏感性、特异性和阴道镜转诊率分别为70.9%、74.3%和27.6%；以HPV作为初筛检测，HPV阳性女性通过VIA进行分流时，其敏感性、特异性和阴道镜转诊率分别为65.9%、95.2%和7.4%。HPV初筛后VIA分流比单独使用VIA要好（P = 0.004）。
考虑到卫生资源状况和女性偏好，HPV初筛后LBC分流和LBC初筛后HPV分流均适用于发达地区，中等发达地区可选择LBC或HPV作为筛查方法，VIA是欠发达地区合适的初筛检测方法，若未来有低成本的HPV检测，HPV初筛后VIA分流将更有效。
