两种新型低成本检测技术在我国农村女性子宫颈癌筛查中的效果评价研究

发布时间：2018-04-25 22:35

本文选题：子宫颈癌 + 筛查　；参考：《北京协和医学院》2014年博士论文

【摘要】：研究目的评价低成本高危型HPV DNA检测技术(careHPV)与E6蛋白检测技术(OncoE6)在我国农村女性子宫颈癌筛查中的效果,分析其影响因素及改进方法,为其在我国农村女性子宫颈癌筛查项目中的推广应用提供参考依据。材料与方法 2010年10月～2012年8月,在我国3个农村地区开展了一项采用6种方法(包括OncoE6、careHPV-S、careHPV-C、HC2-S、HC2-C及VIA)联合筛查子宫颈癌的前瞻性研究,将所有筛查阳性者及约10%筛查阴性者均转诊进行第2次VIA及阴道镜检查,并按方案要求进行活检和ECC。1年后,对所有基线筛查阳性者及约20%基线筛查阴性者进行随访。我们分析了人群中HPV感染和E6蛋白表达情况的年龄趋势,并解释了出现HR-HPV感染第二高峰的主要原因；评价了careHPV和OncoE6在人群初筛中的效果及影响因素,并通过汇总另一项名为快速子宫颈癌筛查技术研究(START)的数据找到careHPV-C和careHPV-S的最佳临界值。最后,我们探讨了不同检测结果人群的发病风险及相应的管理办法。研究结果 1.HPV感染与E6蛋白的年龄趋势分析：HR-HPV、HPV16/18/45和E6蛋白阳性率分别为13.1%、2.9%和1.0%,其中HR-HPV感染率在55～59岁女性中达到峰值19.3%,而HPV16/18/45与E6蛋白的阳性率均随年龄增加而上升,在55～65岁女性中HPV与E6蛋白的阳性率均较高。HR-HPV的清除感染率随年龄增加而下降,但新发感染率的变化与年龄无关,不同年龄组HR-HPV感染的危险因素不同。 2.两种方法在子宫颈癌初筛中的效果：careHPV在医生取样标本中的检出效果优于自我取样标本。careHPV-C、HC2-C、careHPV-S和HC2-S筛查CIN3+的灵敏度分别为97.0%、97.0%、83.8%和90.9%；特异度分别为86.8%、86.6%、86.5%和83.1%。OncoE6与VIA的灵敏度相似(53.5%与50.5%),但特异度更高(98.9%与93.4%), OncoE6的阳性预测值最高(40.8%)。4种HPV DNA检测的灵敏度基本不随年龄变化而发生改变,OncoE6的灵敏度随年龄增加而上升,VIA的灵敏度则随年龄增加而下降,在45～65岁女性中OncoE6的灵敏度高于VIA。 3. careHPV的最佳临界值分析：汇总数据显示,careHPV-C与HC2-C筛查CIN3+的ROC曲线下面积相似(0.948和0.954),均优于careHPV-S (0.878)。HC2-C、 careHPV-C和careHPV-S的最佳临界值(单位：RLU/CO)分别为1.40、1.74和0.85=careHPV-C的临界值从1.0提高到2.0时,灵敏度变化不大而特异度明显升高。3种筛查方法在大、小年龄组之间的筛查效果相似,但是医生取样HPVDNA检测在小年龄组女性中的最佳临界值较高。 4.筛查阳性人群的管理方法：较高病毒载量(即≥10RLU/CO)的careHPV-C. careHPV16/18/45-C和OncoE6均能有效预测1年内CIN3的发病风险(RR值≥50);careHPV-C阴性者1年内发生CIN3的风险极低(0.1%,95%CI:0.0-0.3)。在careHPV-C阳性人群中,采用≥10RLU/CO、careHPV16/18/45、OncoE6、阴道镜和VIA分流后筛查CIN3+的灵敏度分别为88.5%、77.1%、54.2%、63.5%和52.6%；特异度分别为44.7%、76.5%、93.8%、84.4%和86.5%。OncoE6的阳性预测值(46.4%)和诊断OR值(17.9)均为最高。除≥10RLU/CO以外,其余分流方法在自我取样标本中的分流效果均与医生取样相似。研究结论 1.我国农村55～65岁女性中HR-HPV、HPV16/18/45及E6蛋白均处于较高水平,值得重视。人群中出现HR-HPV感染第二高峰现象的主要原因包括：(1)队列效应；(2)大年龄女性中的新发感染率较高；(3)大年龄女性中的清除感染率较低。 2. careHPV是适用于我国农村地区的子宫颈癌初筛方法。取样方法和检测临界值会影响careHPV在人群中的筛查效果,其中医生取样标本的检测效果优于自我取样标本,两者的最佳临界值分别为2.0RLU/CO和1.0RLU/CO,年龄是影响最佳临界值的一个因素。 3. OncoE6在人群初筛中的效果优于VIA,并且年龄越大筛查效果越好。增加对我国子宫颈癌中常见HPV型别的检测可以提高OncoE6的灵敏度。 4.较高病毒载量的careHPV阳性者、careHPV16/18/45阳性者及OncoE6阳性者发病风险高,应该采取积极的防治态度；而对careHPV阴性者则可以适当延长其筛查间隔。careHPV阳性人群的分流方法各有利弊,应综合考虑各地的卫生资源、经济状况及筛查重点选择适当的方法。
[Abstract]:research objective
To evaluate the effect of low cost high risk HPV DNA detection technology (careHPV) and E6 protein detection technology (OncoE6) in the screening of cervical cancer in rural women in China, analyze its influencing factors and improve methods, and provide reference for the promotion and application of the cervical cancer screening project in rural women in China.
Materials and methods
From October 2010 to August 2012, a prospective study was carried out in 3 rural areas of China with 6 methods (including OncoE6, careHPV-S, careHPV-C, HC2-S, HC2-C and VIA) for cervical cancer screening. All the screening positive persons and about 10% negative individuals were transferred to second VIA and colposcopy, and the program was required to be performed. After ECC.1 years, all baseline screening positive persons and about 20% baseline screening negative people were followed up. We analyzed the age trends of HPV infection and E6 protein expression in the population, and explained the main reasons for the emergence of the second peak of HR-HPV infection, and evaluated the effect and influence factors of careHPV and OncoE6 in the screening of the population. The best critical value of careHPV-C and careHPV-S was found by a summary of the data of the rapid cervical cancer screening study (START) study. Finally, we explored the risk and management of different results of the population.
Research results
The age trend analysis of 1.HPV infection and E6 protein: the positive rates of HR-HPV, HPV16/18/45 and E6 were 13.1%, 2.9% and 1%, respectively, of which the peak value of HR-HPV infection reached 19.3% in 55~59 year old women, while the positive rate of HPV16/18/45 and E6 protein increased with age, and the positive rate of HPV and E6 protein in 55~65 year old women were higher.HR-H. The infection rate of PV decreased with age, but the change of new infection rate was not related to age. The risk factors of HR-HPV infection in different age groups were different.
2. the effect of two methods in the initial screening of cervical cancer: careHPV was better than the self sampling specimen.CareHPV-C, HC2-C, careHPV-S, and HC2-S were 97%, 97%, 83.8% and 90.9%, respectively, and the specificity was 86.8%, 86.6%, 86.5% and 83.1%.OncoE6 were similar to VIA, respectively (53.5% and 50. .5%), but the specificity was higher (98.9% and 93.4%), the positive predictive value of OncoE6 (40.8%) the sensitivity of.4 HPV DNA detection did not change with age, the sensitivity of OncoE6 increased with age, and the sensitivity of VIA decreased with age, and the sensitivity of OncoE6 in 45~65 year old women was higher than VIA..
3. careHPV's optimal critical value analysis: the aggregated data show that the area under the ROC curve of the careHPV-C and HC2-C screening CIN3+ is similar (0.948 and 0.954), which are superior to careHPV-S (0.878).HC2-C, and the optimum critical value of careHPV-C and careHPV-S (unit: RLU/CO) is the sensitivity change from 1 to 2 when the critical value of 1.40,1.74 and 0.85=careHPV-C is increased from 1 to 2, respectively. The screening effectiveness of.3 screening methods was similar in large and small age groups, but the best critical value of HPVDNA detection in small age groups was higher than that of small age groups.
4. the management methods of screening positive people: high viral load (or more than 10RLU/CO) careHPV-C. careHPV16/18/45-C and OncoE6 can effectively predict the risk of CIN3 in 1 years (RR value > 50); careHPV-C negative individuals have a very low risk of CIN3 in 1 years (0.1%, 95%CI:0.0-0.3). In careHPV-C positive population, careHPV16/18/ is greater than 10RLU/CO, careHPV16/18/ 45, OncoE6, colposcopy and VIA shunt screening CIN3+ sensitivity were 88.5%, 77.1%, 54.2%, 63.5% and 52.6%, and the specificity was 44.7%, 76.5%, 93.8%, 84.4% and 86.5%.OncoE6 (46.4%) and the diagnostic OR value (17.9) were the highest. Except for more than 10RLU/CO, the distributary effect of the other distributary methods in the sample samples were all The doctors were similar in sampling.
research conclusion
1. of the 55~65 year old women in rural areas of China, HR-HPV, HPV16/18/45 and E6 are all at a high level. The main reasons for the second peak of HR-HPV infection in the population include: (1) the queue effect; (2) the new infection rate in the older women is higher; (3) the rate of scavenging infection among the older women is lower.
2. careHPV is a preliminary screening method for cervical cancer in rural areas of China. Sampling method and detection critical value will affect the screening effect of careHPV in the population. The results of sample samples by doctors are better than those of self sampled specimens. The best critical values are 2.0RLU/CO and 1.0RLU/CO, and the age is the best critical value. A factor.
The effect of 3. OncoE6 in the screening of the population is better than that of VIA, and the older the screening results, the better. Increasing the detection of common HPV types in cervical cancer in China can improve the sensitivity of OncoE6.
4. careHPV positive people with high viral load, careHPV16/18/45 positive and OncoE6 positive people have high risk of disease and should take a positive attitude to prevent and cure, while those with careHPV negative can appropriately extend the methods of distributary of.CareHPV positive people at screening interval. The health resources, economic conditions and screening should be taken into consideration. Choose the right way.

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R737.33

【参考文献】