DNA定量分析用于宫颈癌及癌前病变的早期筛查探讨

[目的]探讨用DNA定量分析和常规细胞学相结合方法而诊断宫颈癌及癌前病变。[方法]对3266名妇女用宫颈刷取材,每例液基薄层制片2张,1张巴氏染色做常规细胞学检查,1张Feulgan DNA染色用全自动DNA倍体分析系统做DNA定量测定。常规细胞学和DNA倍体分析系统可疑的妇女在阴道镜下行宫颈组织学活检。[结果]3266例宫颈癌标本中,常规细胞学发现42例非典型鳞状上皮（ASCUS）,9例低级别鳞状上皮内病变（LSIL）及1例高级别鳞状上皮内病变（HSIL）。DNA倍体分析发现3个或3个以上〉5C细胞的35例。32例活检病例中有14例宫颈上皮内瘤变2（CIN2）或CIN2以上级别改变,这14例细胞标本中均可见DNA倍体异常,而常规细胞学发现1例正常,8例ASCUS,4例LSIL和1例HSIL。[结论]DNA倍体分析与常规细胞学相结合方法可提高宫颈癌及癌前病变的阳性率。     

DNA倍体分析技术在门诊患者子宫颈癌筛查中的作用

目的 探讨DNA倍体分析在门诊患者子宫颈癌筛查中的应用价值.方法 对门诊行子宫颈癌筛查的2 692例女性就诊者同时进行液基薄层细胞学检查、DNA倍体分析,对其中可疑病变者840例进行子宫颈活组织检查.对参与子宫颈癌普查的妇女进行液基薄层制片,分别进行巴氏染色和Feulgen染色,由细胞学医师对巴氏染色片作常规细胞学诊断,应用全自动DNA倍体分析系统对Feulgen染色片进行自动扫描诊断.结果 840例患者子宫颈活组织病理检查结果分别为：慢性子宫颈炎554例（66.0％）,子宫颈上皮内瘤变（CIN）Ⅰ 25例（3.0％）,CINⅡ59例（7.0％）,CINⅢ100例（11.9％）,子宫颈癌102例（12.1％）.DNA倍体分析中可见DNA异倍体细胞者（DNA异倍体细胞阳性）486例,未见DNA异倍体细胞者（DNA异倍体细胞阴性）354例;DNA异倍体细胞阳性、异倍体细胞≥3个用于筛查CINⅡ及以上病变的敏感度、特异度、阳性预测值、阴性预测值分别为91.9％和89.2％、58.5％和35.8％、49.4％和57.3％、94.1％和77.2％;采用液基薄层细胞学检查LSIL及以上用于筛查CINⅡ及以上病变的敏感度、特异度、阳性预测值、阴性预测值分别为40.2％、90.0％、39.6％和76.9％.结论 DNA倍体定量分析技术较常规细胞学敏感性高,可作为子宫颈癌普查的指标之一.     

P16/Ki-67双染联合DNA倍体分析在ASCUS分流诊断中的应用价值

目的： 探讨P16/Ki-67双染联合DNA倍体分析在宫颈意义不明的不典型鳞状细胞（ASCUS）分流诊断中的应用价值。方法： 选取2016年12月-2018年8月上海市长宁区妇幼保健院收治的经液基细胞学（LCT）诊断为ASCUS的患者115例，同时行P16/Ki-67双染检测，DNA倍体分析，且以阴道镜病理活检结果为金标准。结果： 115例患者阴道镜病理活检结果提示，宫颈上皮瘤变2级及以上（CIN2+）45例，其中CIN2级20例，CIN3级23例，鳞癌2例；P16/Ki-67双染检测CIN2+的灵敏性、特异性、诊断符合率分别为77.8%、77.1%、77.4%；DNA倍体分析检测CIN2+的灵敏性、特异性、诊断符合率分别为71.1%、34.3%、48.7%，且DNA倍体阴性的细胞标本中P16/Ki-67双染检测结果均为阴性；DNA倍体分析联合P16/Ki-67双染检测CIN2+的灵敏性、特异性、诊断符合率分别为92.9%、71.4%、86.3%，其中诊断符合率明显高于单纯采用DNA倍体分析（P < 0.05）。结论： P16/Ki-67双染相较于DNA倍体分析检测CIN2+具有更高灵敏度和特异度，两者联合检测能有效提高准确率，可辅助用于ASCUS的分流诊断。     

P16/Ki-67双染联合DNA倍体分析在ASCUS分流诊断中的应用价值

目的： 探讨P16/Ki-67双染联合DNA倍体分析在宫颈意义不明的不典型鳞状细胞（ASCUS）分流诊断中的应用价值。方法： 选取2016年12月-2018年8月上海市长宁区妇幼保健院收治的经液基细胞学（LCT）诊断为ASCUS的患者115例，同时行P16/Ki-67双染检测，DNA倍体分析，且以阴道镜病理活检结果为金标准。结果： 115例患者阴道镜病理活检结果提示，宫颈上皮瘤变2级及以上（CIN2+）45例，其中CIN2级20例，CIN3级23例，鳞癌2例；P16/Ki-67双染检测CIN2+的灵敏性、特异性、诊断符合率分别为77.8%、77.1%、77.4%；DNA倍体分析检测CIN2+的灵敏性、特异性、诊断符合率分别为71.1%、34.3%、48.7%，且DNA倍体阴性的细胞标本中P16/Ki-67双染检测结果均为阴性；DNA倍体分析联合P16/Ki-67双染检测CIN2+的灵敏性、特异性、诊断符合率分别为92.9%、71.4%、86.3%，其中诊断符合率明显高于单纯采用DNA倍体分析（P < 0.05）。结论： P16/Ki-67双染相较于DNA倍体分析检测CIN2+具有更高灵敏度和特异度，两者联合检测能有效提高准确率，可辅助用于ASCUS的分流诊断。     

p16INK4a免疫细胞化学检测在筛查宫颈癌中的作用

目的 探讨p16^INK4a免疫细胞化学检测在筛查宫颈癌及其癌前病变中的作用。方法 选择220例宫颈液基细胞学剩余标本,制作液基薄片进行p16^INK4a 免疫细胞化学检测,随访组织活检结果,并与高危人乳头瘤病毒（HR—HPV）DNA检测结果进行对照。结果 p16^INK4a在宫颈细胞学诊断的鳞状细胞癌（SCC）、鳞状上皮内高度病变（HSIL）、鳞状上皮内低度病变（LSIL）、非典型鳞状细胞-小除外上皮内高度病变（ASC—H）和非典型鳞状细胞-不能明确意义（ASC—US）病例的阳性表达率分别为100．0％（7／7）、92．2％（107／116）、24．3％（17／70）、100．0％（14／14）和36．4％（4／11）。150例p16^INK4a阳性者中,111例有组织活检诊断,其中宫颈上皮内瘤变（CIN）2级及以上病变者97例（87．4％）;70例p16^INK4a阴性者中,18例有组织活检诊断,无一例CIN2及以上病变。p16^INK4a在CIN2及以上病变与在CIN1之间的阳性表达率差异有统计学意义（P〈0.01）,而HR-HPV DNA的阳性率在两者之间差异无统计学意义。结论 p16^INK4a在宫颈HSIL及以上病变中高表达,有利于高危病例的筛选。     

超薄细胞检测及TBS分类法在宫颈癌筛查中的应用

[目的]对超薄细胞检测系统(thinprep pap test,TPTP)及Bethesda(TBS)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]对进行TPT检查及TBS细胞学分类的1209例临床资料进行回顾性分析。[结果]标本满意率93．38％；鳞状上皮异常96例中，未明确诊断意义的鳞状细胞(ASCUS)14例；低度鳞状上皮内瘤变(LSIL)55例，活检证实CINⅠ-Ⅱ级46例(83．64％)，CINⅢ级2例(3．64％)；高度鳞状上皮内瘤变(HSIL)10例，活检证实CINⅢ级及原位癌8例(80％)，CINⅠ-Ⅱ级1例(10％)，鳞癌早浸1例(10％)；TBs诊断为鳞癌者17例，均经病理证实，准确率100％。超薄涂片找到腺癌4例，经活检证实宫颈腺癌2例，子宫内膜癌1例．卵巢癌宫颈转移1例，未明确诊断意义的腺细胞(AGCUS)2例病理均阴性；不典型腺上皮3例，活检及诊刮结果为子宫内膜癌1例，宫颈腺癌1例，阴性1例。[结论]TPT技术应用于宫颈癌筛查能明显提高涂片满意率及宫颈异常细胞检出率。TBS报告方法内容直观、易懂、具体，便于细胞学医生与临床医生之间的沟通．增加了标本的可信度。     

液基细胞学筛查宫颈癌的研究

目的 评价ThinPrep液基细胞学在宫颈癌高发区筛查的准确性。方法 1997年例受检者同时做宫颈脱落细胞液基标本采集和阴道镜活检,用液基标本做薄片细胞学诊断和肿瘤相关人乳头瘤病毒（human papilloma virus,HPV)检测。细胞学诊断采用TBS分级系统,阳性诊断包括意义不明的不典型鳞状细胞（ASCUS）以上病变,诊断结果与阴道活检诊断和肿瘤相关HPV DNA阳性检出率对照。所有检查均双盲进行。结果 ThinPrep液基细胞学检出100％（12／12）的鳞状细胞癌（SCC）;93．2％（69／74）的鳞状上皮内高度病变（HSIL）,其中CIN396．8％（30／31）,CIN90．7％（39／43）;72．4％（92／127）的鳞状上皮内低度病变（LSIL）。SCC和CIN3的分级准确率分别达100％和87．1％。HPVDNA阳性检出率与细胞学分级密切相关,且在细胞学与组织学相同级别基本一致。结论 宫颈液基标本收集方法有利于细胞学和肿瘤相关HPV DNA双重检查。ThinPrep液基细胞学检查敏感性高,尤其是对鳞状上皮内高度病变。     

实时光电学设备TruScreen~筛查宫颈癌的临床价值

目的评价实时光电学设备TruScreen检测技术在人群宫颈癌筛查中的价值。方法研究对象为2007年3月至2007年12月参加北京大学深圳医院针对深圳市贫困女性进行的宫颈癌筛查的妇女391名,年龄20～67岁。对所有接受筛查的妇女采用实时光电学设备TruScreen进行宫颈癌筛查,并采集宫颈脱落细胞,以液基细胞学技术行宫颈细胞学检查,以第二代杂交捕获(HC-Ⅱ)技术进行高危型HPV-DNA(HR-HPV)检测。筛查同时行阴道镜检查,对阴道镜疑诊低度鳞状上皮内病变(LSIL)及以上病变者,在可疑病变处取活检。为客观评价各种筛查方法,对各检测结果均采取盲法保存,于各检测结果确定后解盲。凡HC-Ⅱ检测HR-HPV阳性伴液基细胞学≥ASCUS,和(或)液基细胞学≥LSIL及TruScreen检查结果阳性,而筛查当时未取活检(阴道镜诊断非LSIL及以上病变)者,均于3个月内再次阴道镜下活检,明确诊断。病理为CINⅡ及以上病变者行宫颈电热圈坏切术(LEEP)手术,并取活检。有多次病理检查者以其中最高级别病理结果为该患者的最终诊断,病理诊断作为本研究4种筛查方法的评价标准。结果病理诊断CIN I 110例、CINⅡ5例、CINⅢ7例、宫颈浸润癌5例;慢性宫颈炎和鳞状上皮化生59例。TruScreen检测阳性率为28.2%;液基细胞学检测无明确诊断意义的鳞状上皮细胞病变(ASCUS)以上为23.3%,LSIL以上为7.2%;HR-HPV阳性率为34.3%。TruScreen、液基细胞学及HC-Ⅱ法HPV检查,各筛查方法对检出≥CINⅡ病变的敏感性、特异性、准确性、阳性预测值和阴性预测值分别为76.5%、77.3%、77.2%、13.3%和98.6%;液基细胞学以≥ASCUS为阳性各筛查评价指标分别为88.2%、79.7%、80.1%、16.5%和99.3%;以LSIL为阳性界值各指标为70.6%、95.7%、94.6%、42.9%和98.6%;HC-Ⅱ法HPV为94.1%、68.5%、69.6、11.9%和99.6%。结论实时光电学设备TruScreen进行宫颈癌初筛,筛查效率指标中虽敏感性不及HC-Ⅱ法HPV检测高,但与宫颈细胞学检查相当。作为一种新的宫颈癌筛查技术,具有检测无创无痛、用时较短、实时报告结果等优点,适用于贫困地区大样本人群筛查。     

106例意义不明确的宫颈不典型鳞状上皮细胞的病理诊断

[目的]探讨意义不明确的宫颈不典型鳞状上皮细胞（atypical squamous cells of undetermined significance，ASCUS）的病理诊断。[方法]对106例细胞学诊断为ASCUS的患者行HPV DNA检测，同时在阴道镜下多点活检。[结果]106例ASCUS患者中慢性炎症81例（76．42％），其中高危型HPV感染20例，占24．69％（20／81）；宫颈上皮内瘤变（CIN）25例（CINⅠ12例，CINⅡ9例，CINⅢ4例），其中高危型HPV感染23例，占92．0％（23／25）；慢性炎症和CIN患者的HPV感染阳性率有显著性差异（P〈0．05），且两型及以上HPV感染阳性率两组也有显著性差异（P〈0．05）。[结论]ASCUS患者行阴道镜下活检结合HPV检测，能进一步明确诊断。     

p63和 Ki67在 CIN 及宫颈癌组织中的表达及意义

目的：探讨 p63和 Ki67在 CIN 及宫颈癌组织中的表达及临床病理意义。方法：采用免疫组化技术（SP 法）检测 p63和 Ki67在30例正常宫颈组织和115例宫颈 CIN 和宫颈癌中的表达。结果：p63和 Ki67在正常宫颈黏膜上皮、CIN I、CIN Ⅱ级、CINⅢ级、浸润癌表达的阳性率分别为6．7％、40．0％、44．0％、76．0％、97．8％和6．7％、35．0％、44．0％、80．0％、100．0％。各级 CIN 与浸润癌相比 p63及 Ki67的表达率差异显著（P＜0．05）;在 CIN 和宫颈癌中 p63的表达与 Ki67的表达呈正相关（P ＜0．05）。p63和 Ki67表达率与临床分期及病理分级有关（P ＜0．05）。结论：p63和 Ki67可作为反映宫颈上皮增生病变程度及生物学行为的指标,对宫颈非浸润性病变与浸润性病变的诊断及鉴别有参考价值。     

Identification of progressive cervical epithelial cell abnormalities using DNA image cytometry

BACKGROUND: The objectives of the current study were to compare the capabilities of conventional cervical cytology and of DNA image cytometry (DNA-ICM) in the prediction of progressive or regressive behavior in atypical squamous cells (ASC), low-grade squamous intraepithelial lesions (LSIL), and atypical glandular cells (AGC). METHODS: One hundred ninety-six women with Papanicolaou (Pap) smears that yielded diagnoses of ASC, LSIL, or AGC were included in a prospective cohort study. Slides were classified according to the Bethesda system. DNA-ICM was performed according to the consensus reports of the European Society of Analytical Cellular Pathology. RESULTS: Reference standard verification was available in 108 patients. The rate of DNA aneuploidy in Pap smears increased significantly from cervical intraepithelial neoplasia 1 (CIN1) (54%) and CIN2 (64.3%) to CIN3 or greater (CIN3+) (83.3%) in subsequent biopsies (P < 0.05). Using ASC, LSIL, and AGC as input cytologic diagnoses and >/= CIN2 as the output histologic diagnosis, the positive predictive values (PPVs) for conventional cytology and DNA-ICM were 35.2% and 65.9%, respectively (P < 0.001). The negative predictive value (NPV) of DNA-ICM was 85.0%. When >/= CIN3 was used as the output histologic diagnosis, conventional cytology had a PPV of 22.2%. The PPV and NPV of DNA-ICM were 43.9% and 93.3%, respectively. CONCLUSIONS: The results of the current study confirmed the prognostic validity of DNA image cytometry for differentiation between progressive and regressive lesions in patients with ASC, LSIL, and AGC diagnoses.     

细胞DNA倍体图像分析在宫颈癌及癌前病变筛查中的应用

目的利用显微图像分析技术对宫颈脱落细胞做DNA倍体检测、分析,以探讨该技术在宫颈癌及癌前病变筛查中的应用价值。方法对619例宫颈脱落细胞样本分别采用常规细胞学镜检和细胞DNA倍体分析法作检测,其中阳性样本患者行组织活检,并将3种检测结果进行对比分析。结果619例样本,常规细胞学镜检共检出ASC—US42例、ASC—H6例、LSIL29例、HSILl8例;采用细胞倍体分析法检出DI≥2．5时,可见DNA倍体异常细胞（1～2个）的样本102例、DNA倍体异常细胞（≥3个）的样本41例、DNA倍体异常细胞（≥25个）的样本14例;48例组织活检样本检出炎症7例、CINI20例,CINⅡ13例、CINⅢ2例、IC6例。CINⅡ～Ⅲ对应TBS系统中的HSIL计算灵敏度为81．0％;对应SIL和对应ASC＋SIL的灵敏度分别为85．7％和100％。HSIL与CINⅡ～Ⅲ比较有非常显著的统计学意义。CINⅡ～Ⅲ对应DNA倍体异常细胞（≥25个）计算灵敏度为66．7％;对应可见DNA倍体异常细胞（≥3个）的灵敏度为100％。DNA倍体异常细胞（≥25个）与CINⅡ～Ⅲ比较也有非常显著的统计学意义。结论细胞DNA倍体图像分析法在宫颈癌及癌前病变筛查中有较高的灵敏度,若联合常规宫颈细胞学检查,可明显提高宫颈癌筛查的质量控制水平。     

Human papillomavirus typing and DNA ploidy determination of squamous intraepithelial lesions in liquid-based cytologic samples

BACKGROUND: Infection by high-risk human papillomavirus (HPV) plays a role in the evolution of cervical carcinoma. Cellular atypia and consecutive DNA content alterations in cytologic samples are consequences of a preexisting viral infection. METHODS: We analyzed the frequency and association of HPV types and the presence of rare cells with abnormally high DNA content. We also evaluated whether these findings support the cytologic diagnosis in 112 routine cases with low and high-grade squamous intraepithelial lesions (LSIL/HSIL) when performed from liquid-based cytologic samples (ThinPrep). For DNA content measurements, laser scanning cytometry was applied and at least 10,000 cells were analyzed. HPV typing was performed by a direct sequencing approach using the consensus primers GP5+/GP6+ and MY09/MY11. RESULTS: Of 112 SIL cases, 110 (98.2%) were HPV positive and 95 (84.8%) had a high-risk type HPV infection. Almost one-half of the cases (46 of 95, 48.4%) with a high-risk HPV infection presented aneuploid squamous cells with greater than 9c DNA content, whereas none of the low-risk HPV-positive or HPV-negative SIL cases showed any aneuploid cells in this range. Although 91.8% of the HSIL cases displayed greater than 9c aneuploid cells, only 7.9% of the LSIL cases were positive for such cells with abnormally high DNA content. CONCLUSIONS: HPV typing and DNA measurements help in the objectivation of cytologic atypia and both can be performed efficiently from the same liquid-based cytologic samples.     

Histopathologic extent of cervical intraepithelial neoplasia 3 lesions in the atypical squamous cells of undetermined significance low-grade squamous intraepithelial lesion triage study: implications for subject safety and lead-time bias.

Cervical intraepithelial neoplasia 3 (CIN3) is the precursor of mostsquamous carcinomas and serves as a surrogate end point. However, small CIN3 lesions are rarely associated with concurrent invasion. We hypothesized that aggressive follow-up for cytology of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) leads predominantly to detection of smaller CIN3 lesions than those usually associated with cancer. We assessed this hypothesis in a masked histopathologic review of 330 CIN3 lesions in the ASCUS LSILTriage Study, focusing on ASCUS referrals. ASCUS referrals underwent randomized management [colposcopy for repeat cytology of high-grade squamous intraepithelial lesion (HSIL), colposcopy for oncogenic human papillomavirus (HPV) detection or repeat HSIL, or immediate colposcopy]; then all were followed with repeat cytology for 2 years, followed by colposcopy and aggressive treatment. We assessed all CIN3 lesions qualitatively and measured 39 of them. CIN3 lesions were overwhelmingly small. Compared with enrollment, lesions found at follow-up or exit involved fewer tissue fragments (P < 0.01) and showed less diffuse gland involvement (P = 0.03). CIN3 lesions found postenrollment after HPV testing involved the fewest tissue fragments [versus immediate colposcopy (P = 0.04) or repeat cytology of HSIL (P = 0.02)], and none showed diffuse gland involvement. The median distal-proximal length was 6.5 mm (median replacement of total epithelium = 5%) in the 39 measured cases. We conclude that CIN3 lesions underlying ASCUS or LSIL generally lack features associated with invasion, particularly if managed using HPV testing, suggesting that aggressive management leads to early detection of CIN3 but probably prevents relatively few cancers in screened populations.     

Validity of combined cytology and human papillomavirus (HPV) genotyping with adjuvant DNA-cytometry in routine cervical screening: results from 31031 women from the Bonn-region in West Germany

Our aim was to improve the accuracy of routine cervical screening by a risk-adapted multimodal protocol with special focus on possible reduction and prognostic assessment of false positive results. A cohort of 31031 women from the Bonn-region in West Germany, median age 36 years, were screened by cytology (conventional or liquid-based), followed by PCR-based HVP detection with genotyping and adjuvant DNA image cytometry, if indicated, in a sequential manner. The true prevalence of high-grade cervical intraepithelial neoplasia and carcinoma (>/=CIN2) was 0.32% in the population as projected from cervical biopsies of 123 women (0.4%), of whom 100 showed >/=CIN2. Sensitivity of the cytology screening program at PapIIID/HSIL threshold for detecting histologically confirmed >/=CIN2 cases was 81%, with specificity, positive predictive value (PPV) and negative predictive value (NPV) of 99, 20.9 and 99.9%, respectively. Of 38 women receiving the complete screening protocol, all the 31 >/=CIN2 cases were correctly detected by cytology alone, 30 by positive high-risk HPV genotype and 30 by aneuploid DNA profile. The combination of the three methods resulted in an up to 6.9% increase in PPV for >/=CIN2 at practically unchanged detection rate with the additional benefit of being able to predict the probable outcome of CIN1 lesions detected as false positives with any single test. Multimodal cervical screening might permit identification of those women with low-grade squamous intraepithelial lesions likely to progress at an earlier and curable stage of disease and lengthen the screening interval in those with transient minor lesions caused by productive HPV infection.     

Human papillomavirus testing using hybrid capture II with SurePath collection: initial evaluation and longitudinal data provide clinical validation for this method

BACKGROUND: Testing for human papillomavirus (HPV) is an integral part of equivocal cervical cytology triage. Clinical validation of non-FDA (Food and Drug Administration)-approved methods is therefore important because of the high volume of such tests and the implications for missed high-grade lesions if test performance is not optimal. METHODS: A preinitiation study and 17 months of follow-up data using Hybrid Capture II (HC II) HPV detection with SurePath (SP) sample collection were analyzed. Results of HPV tests on abnormal cytology samples were collected and compared with follow-up results. HPV-positive rates were determined in cases of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL), and follow-up rates of cervical intraepithelial neoplasia (CIN) were determined in HPV-positive and -negative cases of atypical squamous cells of unknown significance (ASC-US). Rates were compared with published data using FDA-validated methods. RESULTS: The preinitiation study showed the test method to be 100% sensitive for the detection of LSIL (20 cases) and HSIL (8). The ASC-US follow-up study (2319 cases with 625 having biopsy results) showed that the rate of CIN III+ in HPV +/- cases was 7.8%/1.4%, and of CIN II+ was 17.5%/4.3%, respectively. The positive predictive values/negative predictive values (PPV/NPVs) (CIN II+) for the test were 17.5%/95.7%, respectively. CONCLUSIONS: Published FDA-validated HPV testing follow-up data show that the expected rates of CIN III+ and CIN II+ in the HPV-negative ASC-US population are 1.4% and 5%, respectively, with PPV/NPVs (CIN II+) of 20%/99%, respectively. By comparison, the present data using HC II with SP show strong similarity, indicating clinical validity for the use of this method.     

Why is high grade squamous intraepithelial neoplasia under-diagnosed on cytology in a quarter of cases? Analysis of smear characteristics in discrepant cases

BACKGROUND: The accuracy of cervical cytology has been questioned due to high false negative rate. In order to improve the sensitivity of cytology it is prudent to analyze the factors which hamper with the diagnosis of high grade lesions. AIMS: To study the cyto-histologic agreement in High grade squamous intraepithelial lesions (HSIL) of uterine cervix and to analyze the smear characteristics in discrepant cases. SETTINGS AND DESIGN: Cervical smears of 100 histology proven cases of Cervical intraepithelial neoplasia III (CIN III) were retrieved and reviewed to study cyto-histologic agreement in the diagnosis of high grade lesions. The discrepant smears, undercalled on cytology, were further analyzed to determine the reasons for misinterpretations. Statistical analysis was performed to find out any significant factors for discrepancies. RESULTS: Cytology was able to correctly identify 74 HSILs while in 26 cases a diagnosis of Low grade squamous intraepithelial lesions (LSIL) or below was given. On review, 16 of these non correlating cases could be reclassified as HSIL on cytology while in 10 the diagnosis of LSIL or less persisted. 12/16 (75%) discrepant cases, reclassified as HSIL represented interpretive errors. Sampling errors (7/10) and air drying (5/10) were more frequent in under diagnosed cases. The statistical analysis did not yield any significant differences in the two review groups. CONCLUSION: 26% of HSIL cases were underdiagnosed on cervical smears. The major confounding factors responsible for under interpretation on cytology included air drying artifacts and metaplastic maturation of abnormal cells.     

DNA cytometry confirms the utility of the Bethesda system for the classification of Papanicolaou smears

BACKGROUND: Developed in 1989, the Bethesda System has largely replaced previous classifications of Papanicolaou (Pap) smears from the uterine cervix. The system is binary, dividing smears into two groups - low-grade, squamous, epithelial lesions (LSIL) or high-grade, squamous, epithelial lesions (HSIL). A third category, atypical squamous cells of undetermined significance (ASCUS), is used to classify minimal cellular changes that do not satisfy the criteria for the low- or high-grade categories. This study was designed to confirm the utility of this binary division and to compare the results with another classification system (the Munich II Nomenclature) that is not binary but contains three divisions or grades for dysplasia - low, intermediate, and high. METHODS: Pap smears were obtained from 593 women with a cytologic diagnosis of dysplasia based on the Munich System. Smears were then classified by the Bethesda System into LSIL or HSIL. Patients were followed for 2 years either with biopsy or repeat cytology. The initial smears were restained by the Feulgen method, and ploidy was evaluated by interactive DNA cytometry. RESULTS: Of 241 cases of LSIL, 39% were diploid, 57% polyploid, and 4% aneuploid. Of 352 cases classified HSIL, 4% were diploid, 17% polyploid, and 79% aneuploid. After 2 years of follow-up, 2 of 108 patients who were biopsied and who were originally classified as diploid progressed to cervical intraepithelial neoplasia/carcinoma in situ (CIN/CIS) whereas 109 of 217 patients who were aneuploid and biopsied were found to have CINIII/CIS. CONCLUSIONS: The two divisions of the Bethesda System, LSIL and HSIL, correlated with ploidy as evaluated by cytometry. Aneuploidy was found to be useful to separate cases of HSIL from those of LSIL as defined in the Bethesda System. Because of the binary division, use of a system with three divisions for dysplasia, such as the Munich II Nomenclature, creates a therapeutic dilemma because a single diagnostic category (usually the intermediate grade) may contain both self-limiting and progressive lesions. DNA cytometry of Pap smears was found to be useful as a routine procedure.     

细胞DNA定量分析技术在宫颈癌筛查中的应用

目的:比较和评估两种宫颈癌筛查方法的应用价值。方法:选取2010年1月至 2013年2月到漳浦县医院进行宫颈癌检查的病例14119例。均为宫颈刷取材,液基方法同时制两张片,一张进行巴氏染色,用于常规细胞学TBS诊断。另一张经Feulgen染色,用于细胞DNA定量分析检测。临床活检取材均在阴道镜指导下进行。结果:共建议活检671例。用于回顾性研究的388例有活检结果。其中有宫颈癌5例,CINⅢ/原位癌38例,44例CINⅡ及137例CINⅠ,其余164例为慢性宫颈炎。以活检结果≥CINⅡ作为宫颈癌前病变的阳性标准,采用细胞DNA定量分析检测的敏感性分别为70.11%与97.7%,而常规细胞学检测的敏感性分别为45.98%与58.62%。同一个标本同时采用两种方法联合检测,敏感性可提高到99.89%。结论:细胞DNA定量分析技术可作为宫颈癌及癌前病变检测的辅助手段。