高危型人乳头瘤病毒载量预测宫颈病变和分流人乳头瘤病毒阳性人群的价值

Value of high risk human papillomavirus viral load in predicting cervical lesions and triaging for high risk （HR）-HPV-positive women

目的评价高危型人乳头瘤病毒（HR—HPV）载量预测宫颈病变的发生风险，及其对HPV阳性人群的分流效果。方法筛查队列来源于1项多中心子宫颈癌筛查项目。采用第2代杂交捕获技术（HC-2）检测的相对光单位与域值比值来衡量HR—HPV病毒载量，按照HR—HPV的病毒载量分为阴性组、低载量组、中载量组和高载量组，按照宫颈上皮内瘤变（CIN）病理诊断分组。采用趋势，检验分析病毒载量与宫颈病变之间的关系，计算并比较基线不同病毒载量组1年内发生CIN2＋的风险，分析不同病毒载量界值预测CIN2＋的效果。结果共纳入基线和随访数据完整的女性2725例。趋势x^2检验结果显示，随着病毒载量的增加，病变的严重程度增加（P〈0．001）。在基线病理诊断正常组和GIN1组中，病毒载量阴性者1年内CIN2＋的发病率为0．11％，而中、高载量者中CIN2＋的发病率分别为3．14％和6．09％，与病毒载量阴性者相比，RR值分别为29．05（95％CI为6．07～138．99）和56．34（95％CI为12．89～246．30）。随着基线病毒载量临界值的升高，随访检出CIN2＋的灵敏度逐渐降低，特异度逐渐升高。当病毒载量临界值为15．00时，1年后需要随访的人数由774例下降到412例，检出CIN2＋的灵敏度为91．30％，特异度为47．94％。结论HR—HPV病毒载量越高，发生宫颈癌及高度病变的风险越高，提高病毒载量界值可以进一步分流HPV阳性人群，从而更合理的分配卫生资源。

Objective To evaluate the value of high risk （ HR）-HPV viral load in predicting cervical lesions and triaging for HR-HPV positive women. Methods The study cohort came from a muhicenter cervical cancer screening program. HR-HPV was detected by hybrid capture 2 （HC-2） assay, and viral load was measured by the ratio of relative light units to cut off （RLU/CO）. Women were divided into 4 groups according to the RLU/CO value, and CIN diagnostic system was used to describe the severity of cervical lesions. Chi-square trend test was used to analyze the association between viral load and CIN. The absolute and relative risks of CIN2 ＋ in different viral load groups were calculated, and the clinical performance to detect CIN2 ＋ at fallow-up by different cut-off values of baseline RLU/CO was also calculated. Results 2 725 women with complete results of both baseline and follow-up were included in this analysis. The severity of cervical lesions increased with the increasing viral load （P 〈 0. 001 ）. In women with normal or CIN1 diagnosis at baseline, the absolute risk of one-year accumulative CIN2 ＋ was 0.11% in the HR-HPV-negative group, compared with 3.14% in the moderate viral load group and 6.09% in the high viral load group, and the relative risk of 29.05 （95% CI： 6.07-138.99） in the moderate viral load group and 56.34 （95% CI： 12.89-246.30） in the high viral load group. Raising cut-off value of baseline HR- HPV viral load to 15.00, RLU/CO decreased the number of women who need to be followed up at one-year from 774 to 412, with the sensitivity of 91.30% and specificity of 47.94% in detecting CIN2 ＋ at follow- up. Conclusions The risk of cervical cancer and precancerous lesions increases with the increasing HR- HPV viral load. Raising the cut-off value of HR-HPV viral load can triage for HR-HPV-positive women, therefore help to allocate the health resources more effectively.