【作者】 王倩；

【导师】 徐爱娣； 徐丛剑； 隋龙；

【作者基本信息】 复旦大学 ， 妇产科学， 2009， 硕士

【摘要】 背景:众所周知宫颈癌是最常见的女性恶性肿瘤之一。大量的研究已证明高危型人乳头瘤病毒(Human papilloma virus,HPV)感染和子宫颈癌及癌前病变的发生、发展密切相关。目前筛查是预防和控制子宫颈癌的主要手段。但许多发展中国家或缺少筛查计划,或有细胞学为基础的筛查计划,却因财力缺乏,难以执行。子宫颈癌的发生率并没有得到控制,局部地区甚至有上升的趋势。2002年世界卫生组织详细调查显示中国仅仅有23%的适龄妇女在三年内参加过妇科检查和细胞学检查。目前国际上推荐最佳的宫颈癌筛查方案是液基细胞学联合HPV检测。由于此方案价格昂贵,在经济欠发达地区难以普遍开展。国内外学者试图寻找简单、廉价和快速可行的检测方法作为广大妇女尤其是贫困地区大规模筛查宫颈癌的替代方法。其中包括了醋酸试验肉眼观察(Visual inspection with acetic acid,VIA)和碘试验肉眼观察(Visual inspection with Logu’s iodine,VILI)。本研究拟从经济有效的角度,以病理结果作为标准,通过探讨醋酸、碘染色肉眼观察对上海市社区妇女宫颈病变的初筛效果,评价其作为社区妇女子宫颈癌及癌前病变初筛工具的价值。方法:1.研究对象:来自上海市虹口区,按人口普查资料选择符合条件的妇女(n=3631人)入选标准:20-60岁,有性生活史,智力健全,非月经期,未孕,无全子宫切除史,无盆腔照射史,非急性生殖系统炎症期,签署知情同意书。2.进行妇科检查,排除急性生殖系统炎症。3.醋酸、碘染色肉眼观察:辅助试剂分别为5%醋酸和卢戈氏液。VIA需在5%醋酸试剂作用宫颈1.5-2.0min时作出诊断。VILI没有时间限制。4.收集宫颈脱落细胞:用于高危型HPV DNA检测(采用HC-Ⅱ方法)和细胞学检查;部分(随机抽取)进行液基细胞学检查(≥LSIL为阳性)与HPV检测(HC-Ⅱ法);其余进行巴氏涂片检查(≥Ⅱb为阳性)。5.子宫颈组织活检(包括ECC)指征:1)VIA、VILI异常者2)细胞学检查异常者;细胞学检查为ASCUS和HPV为阳性者行阴道镜检查与定位活检,即使阴道镜检查未见异常,但细胞学检查≥ASCUS或HPV为阳性者均于宫颈四象限取活检。3)筛查阴性者如自愿活检亦予以对照活检。6.治疗和随访:经活检后病理证实有子宫颈病变者,要求病理异常者1月内就诊。VIA、VILI、高危型HPVDNA检测、液基细胞学检测结果为阳性,但经病理证实为组织学阴性,或未做病理活检的对象进入规范随访。7.统计方法:应用SPSS11.0软件对接受检查并有病理结果的患者进行数据处理和统计分析。比较VIA、VILI、巴氏涂片、薄层液基细胞学、HR HPVDNA检测的灵敏度、特异度、假阳性率、假阴性率(漏诊率)、阳性预测值、阴性预测值和约登指数等指标。显著性分析采用X~2检验。P＜0.05,差异有显著性。结果:1、入选此次研究共有3631名适龄妇女(20-60岁),平均年龄46.3岁。问卷调查显示筛查妇女可接受的体检自费金额平均为284.3元。本次筛查早期治疗时效符合率=100%。子宫颈癌前病变及癌(≥CINⅠ)的现患病率为1845人/10万,子宫颈高度鳞状上皮内瘤病变及癌(≥CINⅡ)的现患病率为854/10万。人群HPV感染率为12.5%(148/1183)。病理为正常或炎症者HPV感染率12.5%(27/216),低度子宫颈上皮内瘤样病变者HPV感染率58.1%(18/31),高度子宫颈上皮内瘤样病变及以上宫颈病变的HPV感染率90.9%(20/22)。正常宫颈组和低度宫颈癌前病变组的HPV感染率差异有统计学意义(X~2=37.77,P＜0.05),低度病变和高度病变之间HPV感染率差异有高度统计学差异(X~2=5.31,P＜0.05)。说明病变程度越重,HPV感染率越高。绝经妇女HPV的感染率与非绝经妇女的HPV感染率相比差异无显著性(X~2=1.84,P＞0.05)。2、病理阳性标准为≥CINII时,VIA、VILI的灵敏度、特异度、阳性预测值、阴性预测值、符合率、约登指数分别为85%、90%;62.8%、57.8%;9%、8.7%;98.9%、99.2%;62.8%、59.1%;0.46、0.48。比较VIA、VILI的灵敏度(X~2=0,p＞0.05)、特异度(X~2=1.50,p＞0.05)、阳性预测值(X~2=0.01,p＞0.05)、阴性预测值(X~2=0.06,p＞0.05)等差异均无显著性。3、比较由有丰富阴道镜检查经验的临床医师与由经过短期培训的社区医生进行VIA与VILI筛查宫颈高度癌前病变及癌的准确性,VIA的灵敏度(P＞0.05,精确概率法),特异度(X~2=0.25)阳性预测值(X~2=0.94),阴性预测值(X~2=0.21),符合率(X~2=0.45)等差异均无显著性(P＞0.05);VILI筛查的灵敏度(P＞0.05,精确概率法),特异度(X~2=0.29)阳性预测值(X~2=0.39),阴性预测值(X~2=0.29),符合率(X~2=0.25)差异均无显著性(P＞0.05)。4、比较绝经组与未绝经组进行VIA筛查宫颈高度癌前病变及癌的(≥CINII)敏感度(20%与94%)、特异度(72.4%与65.6%)、阳性预测值(5.8%与19.7%)、阴性预测值(91.3%与99.2),二组之间的灵敏度(P＜0.05,精确概率法)、阴性预测值(X~2=4.87)差异有统计学意义;特异度(X~2=0.93)、阳性预测值(X~2=1.06)无显著性差异。5、HR HPVDNA检测、液基细胞学检查、巴氏涂片筛查高度宫颈癌前病变的灵敏度分别为90.9%、84.6%、38.9%;特异度分别为81.8%、73%、97.4%;阳性预测值分别为31%、29.7%、41.2%;阴性预测值分别为99%、97.4%、96.7%;约登指数分别为0.73、0.6、0.36。6.、VIA的灵敏度高于巴氏涂片的灵敏度,特异度较其低,差异有显著性。VIA与液基细胞学检查的灵敏度、特异度无显著性差异;VIA与HR HPVDNA检测的灵敏度无显著性差异,HPVDNA检测的特异度优于VIA。结论:1、VILI与VIA比较二者筛查宫颈高度癌前病变及癌的准确性相当。VILI不存在VIA作用的时间限制问题。2、研究认为醋酸、碘试验肉眼观察筛查宫颈癌及高度癌前病变的灵敏度较好,漏诊率低。肉眼观察对绝经筛查对象与未绝径者的筛查效果是不同的,不推荐应用于绝经妇女。醋酸、碘试验肉眼观察容易培训,易为广大社区基层医生所掌握,无诊断经验的医生也能达到较好水平。VIA、VILI成本较低,可以反复进行,无需实验室人员和设备,为即查即治,可减少失访。醋酸、碘试验肉眼观察不失为一种适宜在基层社区医疗机构开展的具有临床价值的初筛方法。3、液基细胞学筛查、HPVDNA检测联合应用可适当延长筛查周期,推荐应用于经济发达地区或人群。更多还原

【Abstract】 As all we know,Cervical cancer is one of the most common malignant tumors among women.A substantial amount of studies have showed that high-risk human papilloma virus(HPV) types were highly relative to the incidence and development of cervical cancer and its precancerous lesion.At present,Screening is still the primary Measure to cervical cancer prevention and control.However,some developing countries lack scree -ning program,while other developing countries couldn’t sustain their cytologybased screening program for lack of financial resources.And in those where the effective screening programmes are not developed,the incidence of cervical cancer is not under control.Unfortunately,the incidence is even ascending in places.At present,liquid-based cytology combined HR HPV DNAdetection is a worldwide rec-ommendatory programme for cervical caner screening.But the programme is too expensive to be used widespreadly in low resource settings.Scholars try to find new methods to screen cervical cancer,which are simple,low cost,feasiable and acceptable,including of Visual inspection with acetic acid and Logu’s iodin e(VIA,VILI).By applying VIA and VILI to community women in shang -hai,Our study is to evaluate if VIA or VILI could be an economical and effective tool for cervical cancer and its precancerous lesions primary screening.Methods:1.Objects:In HongKou District of ShangHai,suitable women were invited to participate in our study.They should satisfy these conditions:age between 20y and 60y,not virgin,not in menses,not pregnant,no hysterectomy and plevic radioactivity therapy history,no acute genital inflammation,informed consent.2.Physical examination:Exclude the women with acute genital inflammation.3.visual inspection with acetic acid and Visual inspection with Logu’s odine:The adjunctive reagents were 5%acetic acid and Logu’s iodine.1-1.5 minute after the application of 5%acetic acid,we should diagnosis it.VILI have no time limit.4.Select the cervical specimens to detect high-risk HPV DNA(HC-Ⅱ),liquid-based cytology(LSIL and worse as positive) and PAP Smear.Part Of group A:select the cervical specimens to detect high-risk HPV DNA(HC-Ⅱ) and liquid-based cytology(LSIL and worse as positive);group B and remaining part of group A:Select the cervical specimens to PAP Smear.5.Indications for cervical biopsy(including ECC):1)Patients with VIA OR VILI positive.2)Patients with LSIL or worse;Patients withⅡb or worse;ASCUS with high-risk HPV DNA positive;3)Patients with Sscreening test Negative Voluntary to biopsy6.Treatment and Follow-Up:Those with pathology positive would be treated immediately.(＜1month),those with cytology or high-risk HPV DNA positive and pathology negative,or with pathology omitted,would be followed up7.Data analysis:SPSS11.0 dealt with the data.Sensitivity,specificity,positive predictive value,negative predictive value,accuracy,youden’s index were calculated.The statistical significance was assessed by chi-square test.P＜0.05.Results:1.3631 women were involved in our study,with average age 46.3. Questionnaires show that women think it is acceptable to pay RMB284.3 to have a medical examination on their own account.In our study,100% women with pathology positive have hospital visit in 1month.Morbidity of cervial cancer and its precancerous lesion(≥CINⅠ) is 1845 /1000,000,Morbidity of cervial cancer and its high precancerous lesion(≥CINⅡ) is 845 /1000,000.The morbidity of HPV infection was 12.5%(148/1183).The morbidity of cervical HPV infection was 12.5%(27/216) in those with histology negative,58.1%(18/31) in those with low-grade CIN,90.9%(20/22) in those with high-grade CIN.There was high statistical significance among the group, severity of cervical disease is positively related with morbidity of HPV infection.There was no statistical significance berween premenopausal and menopausal women.2.The sensitivity of VIA for detecting cervical cancer and its high precancerous lesion was 85%,specificity 62.8%.The sensitivity of VILI was 90%,specificity 57.8%.There was no statistical significance in each index.3.Accoding to different manipulators,the sensitivity and specificity of VIA and VILI for detecting cervical cancer and its high precancerous lesion have no statistical significance between experienced group and inexperience group.There was no statistical significance between them in each index.4、the sensitivity and negatice predictive value of VIA for detecting cervical cancer and its high precancerous lesion have a high statistical significance between premenopausal and menopausal group.There was no statistical significance between them in specificity and positive predictive value.5.The sensitivity of HRHPV-DNA detection was 90.9%,specificity 81.8%,negative predictive value99%,positive predictive value 31%,Youden’s Index0.73.The sensitivity of liquid-based cytology(LSIL and worse as positive) was84.6%,specificity73%,negative predictive value97.4%,positive predictive value29.7%,Youden’s Index0.6.The sensitivity of PAP Smear was38.9%,specificity97.4%,negative predictive value96.7%positive predictive value41.2%,Youden’s Index0.36.6.The specificity of VIA and PAP Smear detection was similar,butⅥA had bigger sensitivity.There was no statistical significance betweenⅥA and liquid-based cytology for detecting cervical cancer and its high precancerous lesion.The sensitivity ofⅥA and high-risk HPV DNA detection was similar,but high-risk HPV DNA detection had bigger specificity.Conclusions:1.The accuracy of VILI andⅥA for cervical cancer and its precancerous lesions screening are similar.ⅥA have time limit while VILI have no.2.The sensitivity and negative predictive value ofⅥA for detecting cervical cancer and its high precancerous lesion have high statistical significance between premenopausal and menopausal women.,SoⅥA and VILIare not applicable to menopausal women.ⅥA and VILI can be mastered easily by LMO(local medical offer),ⅥA and VILI are low cost,can be done repeatedly without equipment and laboratory workers.And it is screening-treat,which can avoid lost of follow up。ⅥA and VILI is a socially acceptable primary screening method and fit for primary community,especially suitable in low resource settings,which have clinical value. 3.Cervical cancer screening Programme containing liquid-based cytology and high-risk HPV DNA can have a longer screening interval and is fit for economically developed region and the wealthy.更多还原