宫颈癌多种筛查方案的研究

A study of cervical cancer screening algorithms

目的 探索适宜我国不同地区的宫颈癌筛查方案,以提高我国妇女宫颈癌的防治水平.方法 利用1999年在山西省襄垣县开展的一项以人群为基础的宫颈癌筛查横断面研究的资料,所有筛查对象均进行了薄层液基细胞学（LBC）、荧光镜检、醋酸染色法（VIA）、阴道镜检查、自我取样人乳头瘤病毒（HPv）检测和医生取样HPV检测等6种宫颈癌筛查方法 ,而且每位筛查对象均有病理诊断结果 .采用筛查试验的串、并联法组合各种筛查技术,比较所得方案识别宫颈高度以上病变[≥宫颈上皮内瘤变（CIN）2]的灵敏度、特异度和阴道镜转诊率等指标,以受试者工作特征曲线（ROC）下面积综合分析各筛查方案.结果 LBC检测以未明确意义的不典型鳞状细胞（ASC-US）为阳性,HPV检测以HPV DNA≥1.0 ps/mi为阳性.在LBC和HPV检测组合方案中,并联初筛方法 （即两者任一项阳性即判断为筛查阳性）的灵敏度为100.O%,特异度为68.6%,阴道镜转诊率为34.4%;LBC初筛HPV分流方法 （即ASC-US者进行HPV检测）的灵敏度为93.0%,特异度为89.9%,阴道镜转诊率为13.7%;HPV初筛LBC分流方法 （即 HPV阳性者进行LBC检测）的灵敏度为91.7%,特异度为93.0%,阴道镜转诊率为10.6%.经ROC分析,LBC初筛HPV分流方法 和HPV初筛LBC分流方法 明显优于单纯并联初筛方法 （P=0.0003;P=0.0002）.单独以LBC或HPV检测作为筛查方案时,以ASC-US或低度病变（LSIL）为筛查阳性的LBC方法 灵敏度、特异度和阴道镜转诊率分别为94.2%、77.3%、25.7%和87.2%、93.5%、10.O%;医生取样HPV检测方法 和自我取样HPV检测方法 的灵敏度、特异度和阴道镜转诊率分别为97.6%、84.8%、18.8%和83.5%、85.9%、17.1%.经ROC分析,医生取样HPV检测方法 优于以ASC-US为筛查阳性的LBC方法 或自我取样HPV检测方法 （P=0.005,P=0.002）.在VIA及其与HPV检测的组合方案中,单独采用VIA筛查方法 的灵敏度为70.9%,特异度为74.3%,阴道镜转诊率为27.6%;HPV初筛VIA分流方法 （即自我取样HPV检测阳性者进行VIA检查）的灵敏度、特异度和阴道镜转诊率分别为65.9%、95.2%和7.4%.经ROC分析,HPV初筛VIA分流方法 明显优于单独使用VIA方法 （P=0.004）.结论 根据地区资源条件和个人意愿,我国经济发达地区可选用HPV初筛LBC分流方法 或LBC初筛HPV分流方法 作筛查手段;中等经济发展水平的中小城市可选用单独以LBC或HPV检测方法 作为筛查手段;VLA是欠发达地区可行的筛查方法 ,在廉价HPV检测试剂盒上市后,可选择HPV初筛VIA分流方法 ,以进一步提高宫颈癌的筛查效力.

Objective 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. Methods 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 （ ≥CIN 2） were compared. Results 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）. Conclusion 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.