--WHO-EUROGIN专家会议总结specialist meeting summary

由欧洲生殖系统肿瘤和感染性疾病组织主办、世界卫生组织（WHO）协办的"第四届国际多学科大会--子宫颈癌全球预防战略"于2000年4月5日至9日在法国巴黎召开。大会涵盖了宫颈癌的各种筛查方法，阐述了其原理及发展过程，并对其进行评价。During 5-9 Apr 2000, The fourth international meeting about cervical carcinoma global prevention stratagem was held in Paris in French, this meeting is held by Europe reproductive system carcinoma institute and supported by world health organization, this meeting including all screening methods about cervical carcinoma, and discuss the principle and development, and evaluate each methods one by one  

宫颈癌细胞学筛查的新动态 new cervical carcinoma screening development

半个世纪以来，Pap涂片作为一种基本的筛查方法被广泛应用，对降低宫颈癌死亡率发挥了重要作用。但是一些学者提到发生在美国的分界线事件，即1987年，一些外行媒体报导与Pap涂片检测相关的诊断准确率问题。像Koss博士所关系的一样，仲裁者和金融家们很长时间以来都很关注这一细胞学专业的问题。因此各个医疗机构致力于改善Pap涂片检查，降低了假阴性，从而降低了诉讼的几率。Verhest博士、Hutchinson博士和McGoogan博士报告了应用液基制片的实验结果。这些报告显示，标本质量明显改进，诊断结果明确，这就使得灵敏度增高，而特异度并不降低。Richart博士强调，它更适合同时检测HPV，衣原体，淋球菌及其他病原体，提高了筛查的成本效益性。Along this half century, Pap cervical smear check is a basic method and used broadly, this have a great effect to reduce the mortality of cervical carcinoma, but some specialists mention about the diagnosis nicety rate of Pap check, and care the false negative rate, so each medical serve institute devote into finding a method to reduce the false negative rate, so that they can reduce the change to be involved into some legal proceedings, three doctors reported a TCT( thinprep cytology test) results, this results show that the quality of detecting the normal and abnormal nicety has improved greatly, and the diagnosis is definite and nicety rate is increased, but specificity doesn’t reduce, it is say the false negative is reduce and at the same time the false positive is not change, they also emphasis that they are more suitable to check HPV, chlamydozoan or other reproductive germ at one time, so it has high cost performance   

M Roy博士阐述了凭借电子医学可以在许多方面改善妇科检查，包括细胞学和阴道镜检查的质量控制，以及对细胞学和阴道镜检查第一和第二次的结果进行直接会诊。J Bishop和Mr J Kelly博士评论了计算机辅助自动化这一技术的现状。随着21世纪的到来，大多数的器械都使用液基准备。诊断结果可由计算机直接报告，或结合医师与计算机结果进行报告。McGoogan博士描述了在医学技术日益发展的环境下，确定新的筛查指标是必要的。简言之，新的检测方法除了要有较高的灵敏度和特异度之外，必须更注重成本效益性。分子诊断学的发展有助于研究子宫颈癌的发病机理，确定具有更高灵敏度和特异度的新标志物。They also mention that they can have female reproductive system check in many ways by using electron medical, include cytology check and colposcope to have quality control, and can recheck one or two times directly, two doctors evaluate electron technology of supporting this diagnosis. Along with 21 century coming, lots of checks have been using liquid base prepare, the computer can give some directly diagnosis or support diagnosis advice, doctors mention that with the rapid developing of science, new screening method is a certain thing, at a word new screening method not only care about false negative or false positive, it also care about cost performance. The development of molecule diagnostics can help to find the disease theory and confirm the low false negative and low false positive immunity symbol of  target antigen   

总之，进年来细胞学筛查方案已经取得了很大成功，但是由于医技人员不足，参加试验的人数也很有限，因而在今后的研究中应该运用有限的人力，医疗仪器以及分子学知识来取得最大的成果。Anyway there are great advance in molecule immunity screening area, but the medical technologist and volunteer is very few, so we must make the best use of these limited resource to get the greatest harvest

HPV检测在子宫颈癌筛查中的作用 the HPV check in cervical carcinoma screening 

在宫颈癌的预防策略中，HPV检测的作用愈来愈受到人们的关注。宫颈癌最主要的病因即为HPV感染，持续性感染高危型别HPV是宫颈癌前病变和宫颈癌发生发展的一个必要条件。In the research of cervical carcinoma, the effect of HPV (human papillomavirus) become more and more important, the most common reason of cervical carcinoma is Human papillomavirus infection, and continuous high risk human papillomavirus infection is the necessary condition of precancerous  pathological changes of cervical carcinoma and cervical carcinoma itself

目前，子宫颈癌前病变的初筛通常通过宫颈涂片的细胞学检查来完成。通过运用液基细胞学和模拟神经网络分析系统进行筛查均可降低假阴性，而不降低特异度。但是，它需要有经验的细胞病理技术人员和一定的医疗设备，成本较高。与此相比，HPV取材和检测技术简单，在各实验室之间较稳定，有高度重复性。几乎所有子宫颈癌中（99.8%）均能检出高危型别HPV，因此子宫颈癌筛查方案可以采用高危型别HPV检测法。Recently the screening of cervical carcinoma precancerous pathological changes normally done through cervical cytology smear, so by using liquid base cytology check and computer analysis technology can reduce false negative of this check but no increase the false positive, but this technology needs cytopathology specialist and certain equipment, the cost will be high, and compare with TCT, HPV check is much cheaper and easier, so it is also more popular and steady among all kinds of lab and can be retest easily, and even all(99.8%) cervical carcinoma case can test those high risk Human Papillomavirus  species, so high risk Human papillomavirus test will be a good and convenient choice of check cervical carcinoma screening    

1. HPV检测作为初筛方法 the HPV check as a general screening method

初筛年龄：年龄小于30岁的妇女，尽管普遍存在原发性HPV感染，但其宫颈的病变程度较轻，因此很少发生子宫颈癌。考虑到这些情况以及对年轻妇女的过度筛查和过度治疗所带来的不良后果，将开始筛查的理想年龄定在30岁。一些国家为了消除30岁之前发生的子宫颈癌，制定医疗政策继续提倡更早期的筛查。但是对HPV感染过程和子宫颈癌自然史的研究，并不支持对年龄小于25岁以及初次性交后8年内的妇女中进行子宫颈癌前病变的筛查。General screen age: as this HPV is a common original infection among those female below 30 years old, but the pathological changes is light and then the cervical carcinoma is infrequency, as considering that excess screening of those woman is not very good and effective, so they just suggest that the proper age of screening the HPV is about 30year old, but some country start to have this screening a little earlier to limit the incidence of cervical carcinoma, but according to natural history of HPV and cervical carcinoma, before 25 years old or during the first 8 years after first time sex action is not suggested

筛查间隔：一些国家对于年龄小于30岁的妇女即开始进行每年一次的细胞学筛查，建议这些国家应该对年龄达到30岁之后的妇女进行筛查，并延长筛查的间隔时间到2-3年。小于30岁的妇女一过性HPV感染发生率较高，有些宿主可在2-8月清除病毒。30岁之后持续性感染水平增高，此时，细胞学和高危型别HPV检测联合试验的灵敏度和阴性预测值增高（99-100%），这就允许将两种检测结果为阴性妇女的筛查间隔延长到8-10年，提高筛查的成本效益。Normally HPV can easily infect those female below 30 years old ,and then be got rid of by one own immunity system in 2-8 months, and after 30 years old, this HPV continuous infection level become higher, and now we use both cytology check and high risk species HPV check the nicety rate ( false negative and false positive both low) increase( 99-100%), this can let those female who has both these two check method normal( negative) recheck every 8-10 years, this can increase the cost performance   

灵敏度：用HPV检测法筛查妇女的宫颈高度癌前病变和癌，其灵敏度高于现在施行的细胞学检测。大多初筛试验中的数据表明，应用HPV检测作为初筛手段对高度癌前病变（CIN3）灵敏度较高（85-98.6%），其阴性预测值也较高（99%-100%）。而同一研究中的细胞学筛查的灵敏度较低，为40%-85%。因而可应用HPV检测作为初筛手段，随后对HPV阳性的妇女进行细胞学检测。这种方法的推广有待进一步研究。About the false negative rate( sensitivity) : the false negative rate about to find the precancerous cervical carcinoma or coma is lower than the cytology check ( such as TCT thinpine cytology test也会包括薄层液基细胞检查吗?), most early stage screening data shows that using Human papillomavirus check as the early stage screening is high sensitive to high precancerous changes, the sensitivity is about 85-98.6%, the negative forecast rate is about 99-100%, (the negative forecast is just about specificity and also is about false positive rate), and the same research, the cytology test is less sensitive  to then, the sensitivity rate is about 40-85%, so hpv can act as the main early stage or general screening method, so we can have some cytology test when the HPV show positive, this method put into wide use should to be consented   

特异度：用HPV检测法筛查妇女的宫颈高度癌前病变和癌，其特异度比现在施行的细胞学检测低。但通过在如下妇女中进行阴道镜检查，可提高联合试验的特异度：（1）不考虑HPV感染状态，但是诊断为高度细胞学改变；（2）细胞学正常但是HPV持续阳性（12月）；（3）细胞学不明确或低度病变和/或HPV阳性。Specificity: is also about false positive, HPV check is not as specifically as cytology test, it is say, the HPV positive is not extra show the precancerous or coma, it is also show that there are not only cancer has the same change in HPV change, so hpv just like a huge circle, and this circle is a little larger than the cancer and precancerous circle, and include the cancer and precancerous circle, we can use the large circle to limit the scope, and then in the little scope, we can find the little scope easier, this is just like criminal detective, but using this kind of check as below can increase the specificity, 1, in spite of HPV infection situation, just diagnosis about highly cytology changes; 2, cytology is normal but HPV continuous positive for 12 months; 3, cytology changes not sure or the changes is low, and/ or HPV continuous positive  

2. HPV检测作为重复筛查的手段：the HPV test act as a retest method

应用子宫颈细胞学检测作为唯一的初筛手段进行筛查，将会出现不确定的诊断（ASCUS或Pap检测边缘值）。通过细胞学检测，大部分妇女结果为正常，约6-11%有高度癌前病变，约1/1000存在子宫颈癌。它只检测到了一小部分Pap异常，尽管可以达到预防子宫颈癌的目的，却造成了一些国家尤其是发展中国家大量的资金浪费。对不明确的Pap涂片进行确诊后的结果也表明，应用HPV检测作为初筛手段有较高的灵敏度和阴性预测值。Using  cervical cytology smear as the only screening method can lead some unsure diagnosis, lots of result is normal in cytology test, but 6-11% precancerous changes, and 0.1% cancer case, they can test out a small part Pap unnormal, and ger the target of prevent cancer, but cost lots of money, use HPV to confirm those unsure case can also show that HPV test is a high sensitivity method.

最近的ASCUS试验研究表明，重复细胞学检测出的高度癌前病变和子宫颈癌的灵敏度比同一项研究中HPV检测低11-15%，但阴道镜转诊数大体相同。虽然重复细胞学检测结果尚让人满意，但即使有经验的阅片者进行细胞学诊断时也会有差异。而在不同的实验室之间进行HPV检测的结果较稳定，因此应用HPV检测作为筛查手段的研究越来越重要。Recently ASCUS research show that compare with HPV the sensitivity of repeatedly cytology check in cancer case and precancerous changes is 11-15% lower, but the transfer treatment rate is the same, clearly that the cytology test can satisfy us, but even those salted specialists can have some different results to same sample, but in different lab, the HPV test result is very steadily, so HPV become more and more important in general screening of cervical carcinoma prevention

基于以上几点，那些有不明确Pap(巴氏检查)结果的妇女最好进行HPV检测，如果HPV阳性，建议作阴道镜检测，HPV阴性的妇女则可以定期参加筛查。目前，标准的筛查计划包括：对于ASCUS-HPV阴性的妇女在6个月后进行重复细胞学涂片检测，由于HPV检测对高度癌前病变和子宫颈癌筛查的灵敏度较高，允许进行常规筛查，不需加快随访次数。Base on those point of above, those whose don’t understand Pap result had better to have HPV screening, if HPV positive, so suggest to have vagina lens test, and HPV negative female can regular screening plan later, to those ASCUS( 不典型鳞状细胞)-but HPV negative case, we can test cytology test again after 6 months later,  because the hpv has high sensitivity to caner and precancerous changes, so we can have regular screening and not add some following up research

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摘要  目的  对液基薄层细胞检测系统（ThinPrep cytology Test，TCT)及巴氏系统（the Behesda system，TPAP)细胞学分类法在宫颈癌筛查中的应用价值进行综合评价。方法  采用液基薄层细胞检测系统检测宫颈细胞并进行TPAP细胞学分类诊断，将诊断意义不明确的不典型鳞状细胞（ASCUS）以上病变均列为阳性病例，且在阴道镜下行活检，将细胞学检测结果与活检结果作对比分析。结果  液基薄层细胞学检测法标本满意率99%，1 002例涂片中阳性病例106例，阳性率4.22%。对76例异常者行阴道镜下活检与组织病理学诊断总符合率81.5%（62/76）。结论  TCT技术应用宫颈细胞涂片筛查，明显提高了涂片的满意率及宫颈异常细胞检出率。TPAP报告方式内容直观、易懂、具体。TCT检查异常的病例配合阴道镜病理检查进行最后诊断，能及早发现宫内早期病变，是防治宫颈癌发生的关键。

　　APPLICATION OF LIQUID BASED CYTOLOGY TEST AND BEHESDA SYSTEM CYTOLOGY SUBDIVISION IN CERVICAL CANCER 

　　Teng Shuwen,He Xiaoli.

　　Hangtian Hospital of Beijing,Beijing 100076,China

　　Key words  uterine cervix cancer; thinprep cytology test (TCT); screening; early diagnosis

APaptract  Objective  To study the value of Thinprep cytology Test (TCT) and the Behesda system(TPAP) cytology subdision in cervix cancer. Methods  1800 cases were detected by TCT and TPAP. The samples of atypical squamoha cell and more abnormal cell were positive, then compared the positive results with colposcopical biopsy examination. Results  The satisfactory rate of TCT smears was 95%,76 samples were positive, the positive rate was 4.33%.Of these 76 cases,62 cases were agreement with the pathological examination, the rate of agreement was 81.5%(62/76). Conclusion  If combined colpiscopical with pharmological examination, TCT could find out the early cervix lesion as soon as possible. The TPAP cytology subdivision is more detailed, simple and direct. It is the key to prophylaxs and treat cervix cancer.

宫颈癌是威胁妇女健康的主要疾病之一，据世界卫生组织报告，宫颈癌的发病率在中国为14.6/10万，特别是近年来有明显上升和年轻化趋势［1］。传统巴氏涂片五级分类诊断法明显减少浸润性宫颈癌的发病率和病死率［2］，但多种文献报道存在假阴性，为6.0%~55.0%［3］。液基薄层细胞学（ThinPrep）检测是细胞学标本制作方法的一次革命，其报告方式采用 the Behesda system(TPAP)系统［4］，因其诊断可靠性高，而成为国内外妇产科宫颈阴道病诊断的常规方法。本文对我院1 002例同时采用传统巴氏涂片法和液基薄层细胞检测法进行对比，旨在综合评价液基薄层细胞检测法在宫颈癌筛查中应用价值。Cervical carcinoma is a common disease which risk to female, and according to WHO, the incidence of cervical carcinoma is about 14/100thousand, and recently the incidence of this disease increase and affected age become younger and younger, and traditional Ba’s classify won’t meet the recently development of this disease, specially the false negative is high, so liquid basic cytology is a revolution of cytology test, and the report use TPAP system,, so it become a common method of international cervical disease method because of its high sensitivity, so this research just to confirm this method with traditional PAP technology

传统巴氏染色及分类法应用半个多世纪以来，为早期诊断子宫颈癌及降低死亡率做出了重要贡献。但由于会出现较高的假阴性率（文献报告为2％～50％）或假阳性率，故该技术目前国外已停止使用，取而代之的是现代宫颈细胞学新技术及TPAP分类法。Traditional PAP dye and classify method have been used for more than half century, and at the beginning of its use, it reduce the mortality, and just because of high false negative, so this method nearly stop to use again, and the liquid basic cytology test and TPAP take the place of it now.

　　现代宫颈细胞学新技术主要包括以下两个方面：modern time the development of cytology mainly in two area, one is test method, use computer to test automatically, this can have high steadily result and reduce the work loading of operator, the other area is about how to collect the cytology sample.

　　第一、美国于上世纪研制成功了计算机辅助细胞检测系统（CCT），也称为细胞电脑扫描，并于1995年经美国FDA批准用于临床。该技术有如下特点：（1）对发现宫颈异常细胞具有高度敏感性，准确性达97％以上，对子宫颈上皮内病变（CIN）、尖锐湿疣及癌百分之百敏感。（2）除能识别细胞外，还能从微生物病原学方面作出诊断，如滴虫、念珠菌、疱疹病毒（HSV）和人乳头状瘤病毒（HPV）感染等。（3）适用于人群普查。Last century USA successfully had computer supporting cell test, it is also called cell computer scan, and was approved by FDA in 1995, this technology has these advances: has high sensitivity to find abnormal cell, and the correct rate will reach 97%, and to cervical in-epidermis changes, condyloma and carcimona the correctly rate is about 100%, 2, can detect microbiology diagnosis, such as bacterias, virus such as HPV, 3, suitable for general check  

　　CCT检查适应症：宫颈糜烂、触血、尖锐湿疣、白带增多、久治不愈及要求查体者。CCT系统记忆了大量正常与异常细胞，对每百张涂片为一组的宫颈涂片进行自动扫描。目前CCT已把可疑检查范围减少到8～15个区域，大大缩短了检查时间。经过计算机将可疑的异常细胞经彩色图像处理并以数字化形式贮存到数码磁带中备检，然后再复验。病理专家先复查每张涂片上磁盘记录的数字化图像，再重点观察筛出的异常细胞图像。最后，按TPAP分类法做出诊断报告。This method can deal with these data automatically and assess the cell by TPAP system

　　第二、由于传统涂片阅片法会出现2％～50％的假阴性率，涂片上存在着大量的红细胞、白细胞、黏液及脱落坏死组织等而影响正确诊断，所以细胞工程专家近年又推出了液基薄层细胞学技术，是一重大革新，即通过去掉涂片上的杂质，直接制成观察清晰的薄层涂片，使阅片者更容易观察。目前有两种设备：（1）薄层细胞学检测系统（TCT）：1996年美国FDA批准用于临床。主要方法是将宫颈脱落细胞洗入有细胞保存液的小瓶中，刮片毛刷在小瓶内搅拌十秒钟，再通过高精密度过滤膜过滤后，将标本中的杂质分离，取滤后的上皮细胞制成直径为20mm薄层细胞于载玻片上，95％酒精固定，经巴氏染色、封片，由细胞学专家用肉眼在显微镜下阅片，按TPAP法作出诊断报告。此法对异常细胞诊断率提高了13％，对低度鳞状上皮以上病变的检出率提高了65％，但该设备一次只能处理一份标本，并在制成薄片后再染色。（2）自动细胞学检测系统test，又称LCT：1999年获美国FDA批准用于临床。方法是将收集的细胞保存液通过比重液离心后，经自然沉淀法将标本中的黏液、血液和炎性细胞分离，收集余下的上皮细胞制成直径为13mm超薄层细胞于载玻片上。每次可同时处理48份标本，同时完成细胞染色。这种技术将阅片范围缩小到直径13mm内（阅片面积为134mm2，而前者为384mm2，传统涂片面积为1375mm2），同时阅片最低时间减少到2.5分钟（前者需5.5分钟，传统法则需7分钟），

明显降低假阴性率。as traditional sample has lots of red cell white cell ,and some broken cell, and some grume, this can affect nicety, so recently the liquid basic cytology test is a great revolution of cytology test, this technology can get rid of some impurity and just let the target cell in the sample so let the reading become easier, now this technology include two methods: TCT, thin cytology, use a liquid collect and concentrate cells and fix in a sample, then reading the sample, the second is automatically cytology test system, LCT, collect cell and deal with 48 samples in one time, and finish dye at the same time,  

　　但液基细胞学技术阅片仍要用肉眼看显微镜读片去判断。而CCT优点是先进、准确、迅速、经济。以上两种技术是分别对阅片方式及制片方法的改良，如果先用液基薄层细胞学技术制备超薄层涂片，再经CCT筛查，则达到更高水平的诊断了。需说明的是，TCT技术尚不能做到这点，而LCT则可以做到这种先进组合，故又称为T－CCT（Thin－liyer＋cct）技术 TCT is a method which reading the sample with eye, and CCT can help to reading sample rapid and automatically by computer, one thing must mention that, TCT can’t use CCT, but LCT can use CCT, so this new combination technology call T-CCT

参考资料：http://www.81988888.com/newsid157833

细胞学诊断TPAP系统:  国际癌症协会推荐的统一细胞学和组织学诊断TPAP诊断系统：cytology diagnosis system: international cancer institute recommend TPAP diagnosis system, 

（1）正常范围；normal

（2）良性反应性改变，包括炎症,宫内节育器及放疗后的反应性和修复性改变； benign changes: includes inflammation, intrauterine device (IUD), postradiotherapy changes

（3）未明确意义的非典型鳞状细胞: Atypical Squamous cell undetermined significance (ASCUS)

（4）鳞状上皮内瘤变（SIL）。鳞状上皮内瘤变（SIL）包括鳞状上皮内低度病变（LSIL）和鳞状上皮内高度病变（HSIL）。LSIL即CINⅠ，HSIL包括CINⅡ和CINⅢ；squamous intracellular lump

（5）鳞状细胞原位癌；squamous cell cancer in situ

（6）鳞状细胞浸润癌；squamous cell soakage cancer

（7）未明确意义的非典型腺细胞；atypical gland cell undetermined significance

（8）腺癌

细胞学诊断巴氏结果分级: Cytology test Pap result

    巴氏Ｉ级：正常涂片中没有不正常细胞。PapＩ: No abnormal cell smear

　　巴氏Ⅱ级：炎症涂片中细胞有异形改变。PapⅡ: Inflammation cell and cell have abnormal changes

　　巴氏Ⅲ级：涂片中的可疑癌细胞有核变质改变，但不能肯定，需要进一步随诊检查确诊。PapⅢ: Cervical smear can find suspected cancerous changes, but not sure, and need to be confirmed by other test

　　巴氏Ⅳ级：涂片中有高度怀疑是恶性的细胞。PapⅣ: The cervical smear can find some highly suspected malign cell

　　巴氏Ⅴ级：涂片中有癌细胞，可肯定是癌症 PapⅤ: Cervical smear can find cancer cell and the cancer is sure

巴氏染色: 染色的目的是使细胞结构清晰，细胞透明度高，便于观察。染色归纳起来有两大类，即常规染色方法和特殊细胞化学染色方法。常用的染色方法有：苏木精伊红染色法(同组织切片染色)、巴氏染色法、绍氏染色法、迈格吉染色等. 巴氏染色法将胞核染为深蓝色；鳞状上皮底层、中层及表层角化前细胞胞质染绿色，表层不全角化细胞胞质染粉红色，完全角化细胞胞质呈桔黄*色；高分化鳞癌细胞可染成粉红色或桔黄*色；腺癌胞质呈灰蓝色；中性粒细胞和淋巴细胞、吞噬细胞胞质均为蓝色；红细胞染粉红色，粘液染成淡蓝色或粉红色. 巴氏染色的特点: 细胞透明度好，结构清晰，涂片色彩丰富而鲜艳，由于能显示鳞状上皮不同角化程度，常用于阴道涂片测定雌激素水平。宫颈涂片和痰涂片中分化差的鳞癌小角化细胞显示桔黄*色，在红色坏死背景中特别突出，不易漏诊。Pap dye: the purpose of dye is to make the cellularity clearer, and the transparence become more clear to observe clear, the dye includes two methods: normal dye and special dye, Pap dye can make cell nucleus deep blue, and cytoplast green and etc. the characteristic of Pap dye: can see more clearly about the cell structure, the color the sample is very vivid, and can show squamous cell different developing stage, and the cancer cell can show a bright yellow color which is very sharing among a red background

　　1  资料与方法

　　1．1  一般资料  随机选择我院体检中心2003年10月—2004年11月已婚妇女1 002例，同时行传统巴氏涂片法和液基薄层细胞检测。年龄25~68岁，有性生活史，无自觉症状，无全子宫切除史和宫颈锥形切除史。

　　1．2  方法

　　1．2．1  传统巴氏涂片法  用木质小脚板在子宫颈外鳞-柱状上皮交界处，顺时针轻刮1周，涂片，放于95%乙醇中固定，染色，镜检。按巴氏五级分类法分类。TCT标本制作：将细胞采集器（特制宫颈刷）插入子宫颈管内围绕子宫颈顺时针方向旋转5周，然后将采集器直接放入盛有ThinPrep细胞保存液小瓶中，经过旋涡振荡使采集器上的细胞进入瓶内液体中，再经过ThinPrep 系统程序化处理，制成新柏氏超薄涂片，95%乙醇固定，巴氏染色，由经专门培训的细胞学医生根据TPAP报告方式做出描述性诊断报告。对涂片质量不满意者重新取材、检验。Pap choice sample around the cervices, and use Pap dye and fix the cell to monitor, and Pap test classify the cell changes into 5 degrees. Thinprep cytology test( TCT), use a special tool to get the sample in the cervices and put the tool totally into a certain liquid and concentrate to make a cell slice, then use Pap dye and fix and classify the cell changes use TST system, the reader needed to be a specialist in cell detective area who had been trained already

　　1．2．2  TCT报告内容和标准与巴氏分级报告内容对比  TCT报告内容和标准：①涂片质量；②微生物项目；③病毒项目；④对细胞改变的描述性诊断。传统巴氏技术共分五级，二者对照见表1。

1．2．3  阴道镜下病理活检  对巴氏Ⅲ级以上和TCT报告ASCUS以上者均行阴道镜下病理活检，分别了解与病理检查结果符合情况。

　　2  结果

　　2．1  TCT细胞涂片异常情况分布  液基薄层细胞检测法标本满意率95%，1 002例涂片中阳性病例106例，阳性率9.2%，其中SCC 0例，高度鳞状上皮内病变（HSIL）6例，低度鳞状上皮内病变（LSIL）32例，不典型鳞状细胞（ASCUS）66例，各类微生物感染中滴虫18例，念球菌38例，细菌性28例，放线菌9例，人乳头状瘤病毒（HPV）感染12例。TCT细胞涂片结果分布，见表1。

　　2.2  巴氏涂片与TCT结果比较  见表2。表2显示TCT阳性率为10.4%，巴氏涂片阳性率为0.001%，前者明显高于后者。

　　2．3  阴道镜活检病例与TCT细胞学诊断比较  见表3。

TCT细胞学检测，HSIL 6例，阴道镜活检后1例为浸润性鳞癌，行宫颈癌根治术;1例为高度病变，行全子宫切除术，3例为低度病变，其中2例行宫颈锥切术；1例为炎症，半年后复查TCT为良性反应性改变。所以HSIL与阴道镜活检阳性符合率为83.3%（5/6）。LSIL 32例，阴道镜活检后1例为HSIL，20例为LSIL，10例为炎症，2例失访，与阴道镜活检阳性符合率为100%（30/30）。ASCUS 66其中42例行阴道镜检查，3例为低度病变，49例为炎症，另外14例要求半年后复查TCT，现正在随访中。

　　表1  TCT细胞涂片结果情况　略

　　表2  巴氏涂片与TCT结果比较（略）

　　3  讨论discussion

　　3．1  应用TCT细胞学检测及TPAP分类诊断的必要性  宫颈癌是威胁妇女健康的主要疾病之一，尤其发展中国家其病死率持续处于女性恶性肿瘤病死率的首位［5］。原因主要是：①处于高危状态的人群未被筛查。②普查率不够。③方法不够准确。④未重视加强有关避免或减少患病危险因素的教育，引起妇女对潜在症状的关注。本组TCT细胞学检测的阳性率及与阴道镜病理检查的符合率均明显高于巴氏涂片法。常规巴氏涂片产生假阴性的原因主要是：①涂片中没有能诊断的细胞或涂片质量差，过多粘液、血液或炎细胞以及上皮细胞过度重叠使不正常细胞被遮盖；②读片工作量大，眼晴过度疲劳，造成镜检漏筛；③认识和判断的错误，假阳性和假阴性的情况再所难免。ThinPrep改变了常规巴氏操作方法，其特制毛刷，具有同时取得宫颈及宫颈管细胞的优点，取材全面满意；标本取出后立即洗入细胞保存液中，避免了常规巴氏涂片过程中遗留在取材器上的细胞随取材器一起被抛弃和细胞过度干燥。进入保存液经程序化处理，随即取样制成均匀的薄层涂片。薄层中的细胞结构和背景清晰利于鉴别诊断。特别是能清楚看见用一般刮片难以看见的柱状细胞；所以，ThinPrep在取材和制片上优势明显。The necessity of TCT and TPAP: cervical carcinoma is a important risk to female health, and it is highest mortality among the female carcinoma disease, the reason is: the person in high risk haven’t been screening; the screening rate is not enough; the method is not correct; not enough education about prevention and let female know the early stage symptom, TCT and cervical lens pathological check is much sensitivity than Pap test, traditional Pap test has high false negative: the quality of sample is not good, there are lots of other cell and material in the sample; the workload is huge and it is easy to make eye fatigue to make thing wrong; the detective and knowledge is not enough and can’t get the right diagnosis, the false negative and false positive can’t avoid, but thinprep cytology test is thin slice and not other cell and material to interrupt the detective area, and at the same time some cell in Pap method normally throw away or destroy without use in time, but in TCT method, the cell which was collect all used in time and concentrate into a slice to be read   

3．2  几种细胞学分类的方法和比较 several cytology method contrast

1）1943年巴巴尼古拉首先提出了子宫颈阴道涂片的巴氏染色及分级法［6］。巴氏I级为正常细胞；II级为不典型细胞，但无瘤样改变；Ⅲ级为可疑恶性细胞；Ⅳ级为高度可疑恶性细胞；V级为肯定恶性细胞。几十年来，临床上采用这一分级系统，大大降低了子宫颈癌的发生率。但其明显的缺点是，以级别来表示细胞学改变的程度易造成一个假象，似乎每个级别之间有严格的区别，使临床医生仅根据分类级别所代表的特定范围来处理患者。事实上，Ⅱ、Ⅲ、Ⅳ级时间的区别没有一个严格的客观标准，主观因素较多。此外，该系统对癌前病变也无明确规定，可疑癌是指可疑浸润性癌还是上皮内瘤变不明确。将不典型细胞全部归类于良性细胞改变也有失妥当，因为病理学家也偶然可见到轻度非典型增生伴微小浸润癌的病例。近10多年的研究表明，轻度非典型增生细胞与原位癌细胞在性质上是相同的，均有肿瘤细胞的形态特点及生物学特性，只是程度不同。因此，巴氏分级已不能适应现代细胞学诊断的要求。The traditional Pap cervical smear and classify, this method have been used for more than half century, this reduce the mortality of cervical carcinoma, but the Pap has high subjectivity and can’t give a determined suggestion, so the Pap can’t meet the modern requirement

2）WHO分类法：①正常细胞涂片。②不典型细胞。鳞状上皮良性增生或炎症所致。③CIN 1级。相当于病理学的轻度不典型增生，指中、表层鳞状上皮细胞核增大，达正常中层鳞状上皮细胞核3倍以上，但不超过细胞总面积的1/3，核染色质呈细颗粒状，分布均匀，轻度深染。④CIN 2级。相当于病理学的中度不典型增生，指中、表层细胞核大小不一致，并出现低层细胞，细胞核进一步增大，但小于细胞总面积的1/2，核/浆比值增加，核轻、中度深染，染色质分布仍然均匀。⑤CIN 3级。相当于病理学的重度不典型增生及原位癌，以中低层细胞为主，细胞小，细胞核增大，占据细胞总面积的2/3以上，核的大小、形态不一致，染色质明显增多，粗颗粒状，深染但分布尚均匀。⑥浸润性鳞癌及腺癌。癌细胞特征明显，伴癌性背景。细胞学检查只是一个筛查方法，而不是最后的诊断，过于肯定的诊断命名可能会产生误导，把细胞学检查结果当成肯定的最后诊断。CIN分级应借助阴道镜检查与形态学诊断结合，才能做出最后评价。

3）为克服以往分类法的缺陷，1988年美国国际癌症协会在马利兰的Bethesda举行会议，提出了TPAP分类法，该法在以下3个方面进行了改良：①将标本质量作为细胞学检查结果报告的一部分。即“满意”、“满意但有缺陷”、“不满意”3类。②引进了鳞状上皮内病变的概念。③提出了治疗建议。描述性诊断包括：①正常细胞学涂片。②良性细胞学改变，包括各类微生物感染、炎症、宫内节育器（IUD）及放疗后的反应性和修复性改变。③鳞状上皮细胞异常。④腺体细胞异常。⑤来源于子宫外的其他恶性肿瘤。其中鳞状上皮细胞异常又分为：①不典型鳞状上皮细胞性质未定，即细胞的异常较反映性改变更明显，但未达到SIL的程度，可以是增生活跃的良性改变或潜在恶性改变，不能对其进行明确分类故而命名。②LSIL相当于轻度不典型增生，同时包括HPV感染。③HSIL相当于中、重度不典型增生及原位癌。④鳞癌。分类方法的对照见表1。TCT检测除提供癌前病变和癌变的诊断外，还能对各种微生物如滴虫、念球菌、细菌、放线菌、HPV病毒感染提供诊断。故对上述疾病的及时治疗有帮助。In order to avoid the traditional classify, in 1988, USA cancer institute has a meeting, they mention TPAP classify method, this method has 3 side improvements: the sample quality is a evaluation side.  2, introduce the idea of squama intracellular pathological changes, and give a clear and detail describing diagnostically idea. 3 give a treatment suggestion

　　本组结果提示，对同一病例，用ThinPrep和传统巴氏涂片检查，前者的阳性率高，对宫颈病变敏感性好，二者比较差异有统计学意义。同时，对TCT结果异常的病例行阴道镜检查，进一步明确诊断，使宫颈病变得到及时治疗，所以说，细胞学检测是宫颈病变的有效的筛查方法，阴道镜下宫颈活检是诊断宫颈病变的可靠方法，联合应用，可提高宫颈病变的诊断率［6］。TCT+阴道镜下宫颈活检是目前诊断宫颈病变的标准模式，能及早发现宫颈的早期病变，是防止宫颈癌发生的关键。According to this research, to the same case, the TCT method comparing with traditional Pap test has high sensitivity, and the two method have a statistical difference, so to say, the cervical smear cytology test is a useful screening method to diagnosis cervical carcinoma, and cervical lens biopsy is credibility method and the standard mode of diagnosis cervical carcinoma in now time, and this can help to find cervical carcinoma in time and provide in time therapy.