农村地区不同子宫颈癌筛查方法的比较

目的比较care HPV与宫颈细胞学联合筛查与单纯使用宫颈细胞学筛查在基层地区人群宫颈癌前病变的检出情况,为政府更好地开展宫颈癌检查提供依据。方法 2014年1-8月在国家农村妇女宫颈癌检查项目县山西省古交市、北京市密云县和河北省曲周县收集7 138例农村妇女,年龄35~64岁并具有当地户口,其中联合筛查组3 536例(采用care HPV检测和液基细胞学联合检查),细胞学组3 602例(单纯采用液基细胞学筛查)。结果联合筛查组检出HPV阳性288例,检出率为8.1%(288/3 536)。检出细胞学异常136例,检出率为3.8%(136/3 536);细胞学组检出细胞学异常111例,检出率为3.1%(111/3 602),两组比较,差异无统计学意义(χ~2=3.122,P=0.077)。联合筛查组CIN2及以上病变检出率(1.2%,43/3 536)与细胞学组(0.6%,20/3 602)比较,差异有统计学意义(χ~2=8.907,P=0.003);联合筛查组CIN3及以上病变检出率为0.6%(21/3 536),与细胞学组(0.2%,9/3 602)比较,差异有统计学意义(χ~2=5.047,P=0.025)。结论 care HPV与细胞学联合筛查检出高级别宫颈病变的检出率明显高于单纯细胞学筛查,而且与其他HPV检测方法相比,其成本相对较低,操作简单方便,适合相对富裕的基层地区。     

内蒙古镶黄旗地区妇女宫颈病变筛查现状

目的探讨宫颈细胞学(包括巴式涂片及超柏氏薄层液基细胞学)及阴道镜检查筛查内蒙古镶黄旗地区妇女宫颈病变的现状及临床意义。方法2004年7月至2009年1月对内蒙古镶黄旗地区的642例28～67岁有性生活妇女进行宫颈病变筛查,其中557例妇女行传统宫颈巴式涂片法,85例妇女行宫颈超柏氏薄层液基细胞学,并对宫颈细胞学异常者(≥ASCUS)行阴道镜检查及活检。结果642例妇女中宫颈细胞学阳性(≥ASCUS)者34例,占5.3%(34/642),其中ASCUS者22例,占64.7%(22/34);低度鳞状上皮内病变(LSIL)者6例,占17.6%(6/34);高度鳞状上皮内病变(HSIL)者6例,占17.6%(6/34),其中有1例肯定为宫颈癌。宫颈细胞学阴性608例,占94.7%(608/642)。宫颈细胞学阳性34例人群中,行阴道镜活检病理检查者有25例,其中慢性宫颈炎13例(52.0%);CIN1为5例(20.0%);CIN2为4例(16.0%);CIN3为1例(4.0%);浸润癌为2例(8.0%)。结论应重视并及时进行经济不发达地区妇女人群宫颈病变的早期筛查,传统宫颈巴式涂片法及阴道镜活检及病理学检查为可行的筛查方法,有条件者可进行宫颈薄层液基细胞学结合阴道镜活检及病理学检查,对提高早期宫颈癌筛查的准确性效果明显。对内蒙古等西部地区,应在完善技术力量支持、筛查质量控制、建立筛查后的转诊制度及治疗的绿色通道等方面,以降低宫颈癌的发病率。     

杂交捕获定量分型技术检测高危型人乳瘤病毒在子宫颈癌筛查中的应用

目的探讨第三代杂交捕获技术定量分型(daltonbio hybrid capture 3,DH3)检测高危型人乳状瘤病毒(human papiloma virus,HPV)在宫颈癌筛查中的应用价值。方法采用DH3和第二代杂交捕获技术(HC2)检测264例宫颈癌筛查女性宫颈脱落细胞的HPV,同时行TCT检查,TCT结果异常者(≥意义不明确的非典型鳞状细胞)行阴道镜下宫颈活检。比较两种方法检测HPV结果的一致性及检出宫颈病变情况。结果 264例女性中,HC2法检出HPV阳性者32例(12.12%)。DH3法检出HPV阳性者39例(14.77%),其中HPV16/18阳性患者14例(35.90%)。264例女性中,DH3和HC2检出HPV结果的符合率为94.32%(249/264);15例结果不一致,其中8例的检测值在临界值,排除此8例后再次统计分析,符合率为97.27%(249/256)。264例中TCT异常者10例,阴道镜下宫颈活检LSIL 1例、HSIL 2例、宫颈癌1例。DH3 HPV16/18阳性女性TCT异常及宫颈病变检出率(71.43%,10/14;21.42%,3/14)显著高于HC2 HPV阳性检出率(31.25%,10/32;9.38%,3/32)(P0.05)。结论 DH3与HC2检测高危型HPV符合率高,DH3 HPV16/18阳性宫颈病变检出率高,DH3技术可作为临床上宫颈癌初筛的有效手段。     

人乳头瘤病毒L1壳蛋白在筛查宫颈鳞状上皮内病变中的应用

目的:探讨人乳头瘤病毒(HPV)L1壳蛋白筛查HPV阳性妇女宫颈脱落细胞中宫颈鳞状上皮内病变的应用价值。方法:选取2012年5月至2014年12月就诊于温州市人民医院的妇女212例,收集宫颈脱落细胞并行HPV L1壳蛋白检测、HPV DNA分型、TCT(液基细胞学)及阴道镜下活检,比较HPV阳性妇女的宫颈脱落细胞中HPV L1壳蛋白的表达情况。结果:212例细胞学标本中HPV L1壳蛋白阳性率为33.9%,其中未见上皮内病变/恶性细胞组(NILM)、无明确诊断意义的鳞状上皮细胞病变组(ASCUS)、低度鳞状上皮内病变组(LSIL)、不能排除高度鳞状上皮内病变组(ASC-H)、高度鳞状上皮内病变组(HSIL)中阳性率分别为47.1%、35.1%、54.2%、29.2%、16.1%,各组比较差异有统计学意义(P0.05);两两比较,HSIL组与LSIL组和NILM组比较,差异均有统计学意义(P均0.005);进行数据合并后,LSIL/ASCUS组与ASC-H/HSIL组比较差异有统计学意义(P=0.001)。178例宫颈细胞学异常患者中,宫颈低级别病变和宫颈高级别病变的HPV L1壳蛋白阳性率比较,在ASCUS组(P=0.000)、LSIL组(P=0.004)中均有差异,在ASC-H组(P=0.127)、HSIL组(P=0.515)中均无差异。HPV 16/18感染患者的HPV L1壳缺失同宫颈高级别病变有更紧密的关系(P=0.003)。结论:子宫颈脱落细胞HPV L1壳蛋白检测在HPV阳性妇女的子宫颈病变筛查中具有一定的价值,可能成为一种合适的分流方法。     

新一代杂交捕获技术在宫颈癌筛查中的应用

目的:了解新一代杂交捕获技术(DH2)在宫颈癌筛查与传统筛查方式的优势比较,探讨HPV16/18分型检测对DH2初筛阳性患者分流管理的临床意义。方法:2013年、2014年、2015年分别对浙江省慈溪市79847例、81702例、61072例妇女采用巴氏涂片的方法进行宫颈癌筛查,在2015年、2016年分别对浙江省慈溪市35657例、59634例妇女使用DH2检测14种高危型HPV的方法进行宫颈癌筛查。以病理诊断作为金标准,分析高危型HPV检测与巴氏涂片在LSIL以上病变的检出率情况。同时对DH2阳性患者进行HPV16/18检测,对照和比较HPV16/18分流策略的检出情况。结果:2013年、2014年、2015年采用巴氏涂片的方法对LSIL以上病变的检出率分别为0.048%、0.105%、0.134%;2015年、2016年使用DH2检测14种高危型HPV的方法对LSIL以上病变的检出率分别为0.415%、0.550%。2015年采用DH2检测14种高危型HPV初筛模式,LSIL以上病变在DH2阳性及在HPV16/18阳性中的占比分别为4.644%、15.370%;2016年采用DH2检测14种高危型HPV初筛及初筛阳性患者HPV16/18分流的模式,LSIL以上病变在DH2阳性及在HPV16/18阳性中的占比分别为6.365%、22.430%。结论:使用DH2检测14种高危型HPV的方法比传统巴氏涂片对LSIL以上病变的检出率更高,DH2可作为宫颈癌初筛的可行方法;DH2初筛及初筛阳性患者HPV16/18分流管理模式对宫颈癌高危人群进行风险分层管理,重点关注HPV16/18阳性人群,可以进一步提高宫颈癌筛查中的LSIL以上病变检出率。     

SIRT-1在不同宫颈组织中的表达及其临床意义

目的:探讨Ⅲ型去乙酰化酶SIRTUIN1(SIRT-1)蛋白在正常宫颈组织及不同级别宫颈病变组织中的表达及其临床意义。方法:应用Western-blot方法及免疫组化(SP)法检测正常宫颈组织(24例)、低级别鳞状上皮内病变组织(LSIL)26例、高级别鳞状上皮内病变组织(HSIL)35例及宫颈癌组织55例中SIRT-1蛋白的表达情况;并分析SIRT-1蛋白的表达与宫颈癌组织各临床病理参数间的关系。结果:(1)SIRT-1蛋白的高表达率在正常宫颈组织为0、LSIL为15.38%、HSIL为37.14%及宫颈癌组织为40.00%,差异有统计学意义(χ~2=16.82,P0.05);(2)宫颈癌组织中SIRT-1蛋白的高表达率在不同组织学分化程度(G1~G3)(χ~2=6.87,P0.05)、有无淋巴结转移(χ~2=7.73,P0.05)、不同临床分期(χ~2=7.39,P0.05)间差异均有统计学意义。结论:SIRT-1随宫颈病变的加重表达逐渐增强,与宫颈癌组织学分化程度、有无淋巴结转移、临床分期有关。可能在宫颈癌的发生和发展过程中起促进作用。     

STMN1联合P16、Ki67蛋白检测对宫颈高级别上皮内瘤变的诊断价值

目的本研究通过测定不同宫颈上皮组织中STMN 1、P16及Ki67蛋白的表达情况,探讨联合上述免疫组织化学检查对高级别上皮内瘤变的诊断价值。方法选取宫颈活检或锥切的宫颈标本共150例(其中宫颈炎组织、LSIL组、宫颈癌组织各30例,HSIL 60例),分别检测STMN 1、P16及Ki67蛋白的阳性表达并行统计学分析。结果 STMN 1蛋白主要在细胞浆内阳性染色,为弥漫性或小片状分布,呈浅黄至棕黄色渐变,STMN 1阳性率分别为宫颈炎组23.33%(7/30)、LSIL 60.00%(18/30)、HSIL 93.33%(56/60)、宫颈癌组100%(30/30),呈正相关趋势,STMN 1在LSIL与在HSIL的表达有显著差异(Diff=23.68,Q=5.26,Q3.633)。结论联合STMN 1、P16及Ki67进行免疫组织化学检查后,较单一免疫组化检查可以更有效的筛选CIN级别,进而提升病理诊断准确率,指导临床治疗。     

荧光原位杂交技术检测宫颈上皮内瘤变及宫颈癌中TERC基因的扩增及临床意义

目的:应用荧光原位杂交(FISH)技术检测宫颈上皮内瘤变(CIN)及宫颈癌中TERC基因的扩增,探讨其在宫颈病变筛查中的意义.方法:筛选门诊就诊宫颈疾病患者宫颈脱落细胞标本120例,其中液基细胞学检查正常者20例,病理学检查CIN Ⅰ、CINⅡ、CINⅢ及宫颈癌各25例.采用双色间期FISH技术检测宫颈脱落细胞TERC基因扩增,以正常标本的检测结果建立阈值.结果:①CIN Ⅰ、CINⅡ、CINⅢ及宫颈癌中每例的异常细胞百分率均大于阈值(P<0.05),异常细胞百分率随病理学分级病变严重程度增高而增高(P<0.01).②2:3、2:4、2:5和4:4以上类型在CIN Ⅰ、CINⅡ、CINⅢ及宫颈癌所占百分率比较,差异有高度统计学意义(均P<0.01),其中宫颈癌与CIN Ⅰ比较,2:3类型所占比例明显下降(P<0.001),2:4、2:5和4:4以上类型所占比例明显升高(JP<0.001).③不同细胞学分级中,异常细胞百分率随其病变严重程度增高而增高(P<0.01),2:3、2:5和4:4以上类型在ASCUS、LSIL和HSIL中的百分率差异有高度统计学意义(均P<0.01),其中HSIL与ASCUS比较,2:3类型所占比例明显下降(P<0.01),2:5和4:4类型所占比例明显升高(P<0.01).④在低级别及高级别CIN中,细胞学LSIL及HSIL检出率分别为10例(40.00%,10/25)及31例(62.00%,31/50),FISH技术检测出低级别与高级别CIN的敏感度均明显高于细胞学检查(P<0.05).结论:CIN Ⅰ、CINⅡ、CINⅢ及宫颈癌均有TERC基因扩增,其拷贝数随病理学及细胞学分级严重程度增加而增加.应用FISH技术检测宫颈脱落细胞TERC基因扩增对宫颈病变筛查及对病变进展预测具有一定价值.     

人乳头瘤病毒E7蛋白检测子宫颈上皮内病变的价值

目的探讨人乳头瘤病毒(HPV)E7蛋白检测宫颈病变的临床应用价值。方法选取180例高危型HPV阳性妇女,采用免疫细胞化学方法检测宫颈脱落细胞HPV E7蛋白。结果 (1)病理高级别宫颈上皮内病变(HSIL)及浸润癌组HPV E7蛋白阳性率(77.8%,56/72)显著高于低级别宫颈上皮内病变(LSIL)组(52.1%,25/48;P=0.003),病理LSIL组阳性率显著高于宫颈炎组(26.7%,16/60;P=0.007);(2)对于细胞学为ASCUS和LSIL的妇女,HPV E7蛋白诊断HSIL及宫颈癌的灵敏度、特异度、阳性预测值及阴性预测值分别为97.1%、52.1%、58.9%和96.2%;(3)HPV E7蛋白和TCT诊断LSIL及以上病变的灵敏度、特异度、阳性预测值、阴性预测值分别为67.5%vs 51.7%、73.3%vs 58.3%、83.5%vs 71.3%、53.0%vs 37.6%,除特异度外,E7蛋白诊断的价值优于TCT(P0.05)。结论 HPV E7蛋白在检测宫颈病变,尤其是在细胞学轻度异常患者的分流中,具有一定的临床应用价值。     

阴道自取样HPV宫颈癌筛查联合宫颈细胞学p16~(INK4a)蛋白检测在精准筛查中的应用

目的探讨阴道自取样人乳头瘤病毒(HPV)宫颈癌筛查模式的有效性及联合宫颈细胞学p16~(INK4a)检测的价值。方法 2018年10—11月对贵州三都水族自治县和北京市门头沟地区3 905名30～59岁女性进行阴道自取样HPV宫颈癌筛查和宫颈细胞学p16~(INK4a)蛋白检测;对14种高危型HPV和p16~(INK4a)蛋白阳性者转诊阴道镜及定位活检,分析高危型HPV和p16~(INK4a)检出宫颈高级别病变(HSIL)及联合检测的效果。结果①3 905名女性阴道自取样本的合格率为100%,14种HPV阳性率16.08%(628/3 905),其中门头沟地区HPV阳性率16.45%(334/2 031),三都水族自治县HPV阳性率15.69%(294/1 874);单一HPV感染占72.77%(457/628);前5位HPV型别依次是HPV52、HPV16、HPV 58、HPV39和HPV68。②593例阴道镜下活检患者中,检出HSIL及以上病变62例(10.46%),其中HPV阳性61例(98.39%,61/62),包括HPV16/18阳性38例(62.30%,38/61),非HPV16/18阳性23例(37.71%,23/61),不同级别病变HPV阳性率比较,差异有统计学意义(P 0.01);③宫颈HSIL及以上病变、LSIL和宫颈炎中p16~(INK4a)蛋白表达的阳性率分别是90.33%、37.64%和19.27%(P 0.001),其检出宫颈HSIL及以上病变的敏感度、特异度、阴性预测值和准确度分别是90.33%、74.58%、98.51%和76.23%,其假阳性率(25.43%)明显低于HPV检测(80.04%)(P 0.001);HPV阳性联合p16~(INK4a)检测,在保持高敏感度(90.17%)的同时,特异度(83.46%)、准确度(84.30%)明显升高(P 0.05),假阳性率(16.55%)明显降低(P 0.05)。结论阴道自取样HPV检测宫颈癌筛查模式是可行的,可作为传统筛查模式的补充。宫颈细胞学p16~(INK4a)蛋白检测可用于对自取样HPV阳性/非HPV16/18的分流或精准筛查的方法。     

Improved cervical cancer screening in premenopausal women by combination of Pap smear and speculoscopy

OBJECTIVE: This study was done to evaluate the efficacy of the Pap smear, speculoscopy, and a combination of Pap smear and speculoscopy (PapSure examination) in pre- and postmenopausal women. STUDY DESIGN: All women were screened using the Pap smear and speculoscopy and combination of both (PapSure examination) in the multicenter trial. Final diagnosis of each patient was based on a histological evaluation of the colposcopic target biopsy. Results were analyzed using a proportional comparison test, sensitivity, specificity, and predictive value with significance determined at p<0.05. RESULTS: Of 1813 women screened, 1701 were eligible for analysis. Two hundred and fourteen women (12.6%) received at least one positive screening test result. Of the 1084 colposcopic biopsy specimens obtained, 24 showed low-grade squamous intraepithelial lesion (LSIL) and 19 high-grade SIL (HSIL). HSIL were considered test-positive. Rate of colposcopy was 21.5% (125/582) in the premenopausal group and 63.9% (321/502) in the postmenopausal group (p<0.001). For premenopausal women, speculoscopy (75.0%) or PapSure (91.7%) provided higher sensitivity than Pap smear (50%) (p<0.05). In postmenopausal women, no statistical significance in sensitivity existed between PapSure (85.7%) and Pap smear (57.1%). Speculoscopy (96.8%) or PapSure (96.5%) had lower specificity than Pap smear (99.6%) (p<0.001). CONCLUSION: PapSure was an accurate alternative screening method to Pap smear or speculoscopy for cervical intraepithelial lesions because of a significantly higher sensitivity along with adequate specificity for premenopausal women; however, PapSure was not a more effective cervical screening method for postmenopausal women.     

Screening for cervical cancer in high-risk populations: DNA pap test or Hybrid Capture II test alone?

This study was designed to evaluate whether Hybrid Capture II (HC2) test alone refer women to colposcopy as appropriately as DNA Papanicolaou (Pap) test, in the context of a high-risk group of women using the recently validated DNACitoliq LBC system. Women with suspected cervical disease were included in this cross-sectional study at a tertiary center in S?o Paulo, Brazil, for further workup. All women had cervical material collected for LBC and HC2 for high-risk human papillomavirus (hrHPV)-DNA test. Irrespective of cytology and HC2 results, colposcopy, and cervical biopsy when applicable, was systematically performed. All tests were performed blindly. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of both methods were computed in relation to histology. A total of 1,080 women were included: 36.4% (393/1080) had ACUS+, 10.2% (110/1080) were high-grade squamous intraepithelial lesions (HSIL) or cancer. Mean age was 33.5 years. All women underwent colposcopy, and cervical biopsies were performed in 38.4% (415/1080): 33% (137/415) of the biopsies were negative, 14.4% (155/415) were low-grade squamous intraepithelial lesions (LSIL), 10.7% (116/415) were HSIL, and 0.6% (7/415) were cancer. HC2 sensitivity to diagnose biopsy-proven HSIL was 100%. Because all HSIL cases had a positive HC2 test, sensitivity could not be improved by adding LBC. Specificity and positive and negative predictive values of DNA Pap were not significantly different from HC2 test alone when considering LSIL+ histology as "gold standard" and HSIL+ histology. As a screening strategy for women with high-risk for cervical cancer, DNA Pap test does not seem to add substantially to HC2 alone in terms of appropriately referring to colposcopy.     

Cervical parakeratosis/hyperkeratosis as an important cause for false negative results of Pap smear and human papillomavirus test

Like any screening method, Pap and HPV tests are subject to false negative results.
Aim: We investigated the possible relationship between cervical parakeratosis/hyperkeratosis and a false negative result for both Pap and human papillomavirus (HPV) testing.
Methods: A total of 551 cases with diagnostically adequate cervical biopsies and Pap tests performed concurrently were examined.
Results: The vast majority of the cases (75.5%) were of concordance in diagnosis. Among the 135 discordant diagnoses were 98 with low-grade squamous intraepithelial lesion (LSIL) biopsy and negative Pap test and 34 with negative biopsy and LSIL Pap test. With rare exceptions, no significant discordance between concurrent biopsy and Pap test was found in the cases of high-grade squamous intraepithelial lesion (HSIL). Cervical parakeratosis/hyperkeratosis was noted in 87.8% of the LSIL biopsies with concurrent negative Pap tests. An 83.3% HPV-negative rate was also observed in this group. By comparison, parakeratosis/hyperkeratosis was less frequent (62.6%) in the SIL biopsies with concordant concurrent SIL Pap tests and usually seen focally when present. The negative HPV rates for these concordant LSIL and HSIL groups were 12.7% and 0.0%, respectively.
Conclusion: Cervical parakeratosis/hyperkeratosis is an important cause for the negative results of Pap and HPV tests in LSIL, and practising gynaecologist and pathologist should be aware of this possible diagnostic dilemma.     

宫颈癌医院机会筛查与社区筛查相关因素分析

目的分析宫颈癌医院机会筛查和社区筛查的相关因素。方法对2008年1月至2008年12月在北京市垂杨柳医院妇科门诊行宫颈癌机会筛查和社区筛查妇女的相关因素进行分析,其中门诊机会筛查7223例（机会筛查组）,社区筛查11539例（社区筛查组）。结果社区筛查组年龄[（45.75±9.29）岁]大于门诊机会筛查组[（33.55±10.49）岁],其中社区筛查组年龄〉50岁者占39.8%,初中及以下文化程度者占96.2%,两组筛查妇女年龄比较,差异有统计学意义（P〈0.001）。两组宫颈鳞状上皮内低度病变所占比例（机会筛查组1.2%;社区筛查组0.4%）比较,差异有统计学意义（P〈0.001）;机会筛查组鳞状上皮内高度病变及宫颈癌发生率高于社区筛查组,但差异无统计学意义（P〉0.05）。机会筛查组不同级别的宫颈上皮内瘤变（CIN）和宫颈癌的检出率均高于社区筛查组,差异有统计学意义（P〈0.05）。结论社区筛查人群年龄较大,文化程度低,应重视这一群体防癌知识宣教,提高筛查率。宫颈癌医院机会筛查与社区筛查同样重要。     

Relative risk of high grade squamous intraepithelial lesion associated with prior abnormal Pap smears

OBJECTIVE: Pap smear frequency remains controversial, especially for women with consecutive negative smears. We undertook the current study to ascertain the association of high grade squamous intraepithelial lesions (HSIL) and prior abnormal Paps. STUDY DESIGN: Women with biopsy-proven HSIL (cervical intraepithelial neoplasia 2 and 3) diagnosed between September 1996 and December 1997 and age-matched controls with a negative Pap obtained during the same time period were selected. RESULTS: Sixty-three cases (mean age = 32 years) of HSIL and 69 controls (mean age = 33 years) constituted the study population. Any prior abnormal diagnosis conferred a 15-fold increased risk of HSIL on the current Pap (50/63 vs. 14/69, P < .0001). When limited to the 60 women with at least three prior Paps, the odds ratio for HSIL on the current Pap with any prior abnormal was 18 (28/31 vs. 10/29, P < .0001). Three cases had at least three consecutive negative Paps prior to the diagnosis of HSIL. CONCLUSION: Women with one or more prior negative Pap smears had a significantly decreased risk of HSIL on the current Pap. Consecutive negative Paps did not appear to further decrease the risk; 10% of HSIL patients had had three or more consecutive prior negative Paps. To detect HSIL at its earliest stage, women should be advised to continue annual Pap screening in spite of consecutive negative results.     

CIN in pregnancy: antepartum and postpartum cytology and histology

OBJECTIVE: To determine the rates of antepartum and postpartum cervical intraepithelial neoplasia (CIN) 2 or worse in pregnant women with abnormal cervical cytology. STUDY DESIGN: A prospective, cohort study of 283 pregnant women referred for colposcopy between 1992 and 1999 for the evaluation of abnormal Pap smears. In this analysis, the population was stratified by severity of referral cytology (atypical squamous cells of undetermined significance [ASCUS] or low grade squamous intraepithelial lesion [LSIL] versus high grade squamous intraepithelial lesion [HSIL] and atypical glandular cells of undetermined significance [AGUS]). RESULTS: Sixty-seven women (24%) had ASCUS, 147 (52%) LSIL, 67 (24%) HSIL and 2 (0.7%) AGUS. As compared to women with HSIL or AGUS, women with ASCUS or LSIL were less likely to undergo antepartum biopsy (relative risk [RR] .34, 95% CI .23-.51) and if biopsied, less likely to have CIN 2 or worse (OR .49, 95% CI .24-.99). Women with antepartum ASCUS or LSIL were less likely to have postpartum HSIL (OR .29, 95% CI, .17-.52) and tended to have fewer histologically severe biopsies as compared to women with antepartum HSIL (OR .55, 95% CI .31-1.05). CONCLUSION: Among those biopsied, pregnant women with mildly abnormal cytology (ASCUS or LSIL), as compared to pregnant women with HSIL, were less likely to have either antepartum or postpartum CIN 2 or worse.     

Prevalence of high-risk human papillomavirus (HR-HPV) types 16 and 18 in healthy women with cytologically negative Pap smear

OBJECTIVE: To study the prevalence of high-risk human papillomavirus (HR-HPV) types 16 and 18 in healthy women with negative Pap smears in identifying women with underlying cervical squamous intra-epithelial (SIL) lesions. METHODS: A total of 3300 women who were attending the Gynecology OPD of Lok Nayak Hospital, one of the major government tertiary hospitals in New Delhi, were screened during a 1-year study period, and 2079 (63%) of them were found to have cytologically negative Pap smear with inflammation and the rest (37%) also had negative Pap report but without inflammation. Hundred and sixty of these sexually active women aged between 20 and 60 years were randomly selected, and were investigated by colposcopy and a guided biopsy was done wherever required. HPV types 16 and 18 DNA was detected in scraped cervical cells from all women using type-specific primers in polymerase chain reaction (PCR). RESULTS: The high-risk HPV (type 16 and 18) prevalence by PCR was found to be 10% (16/160). Histopathological findings were obtained in 123 women, out of which 15 had LSIL and four had HSIL. High-risk HPV types 16/18 could be detected in nine out of these 19 (47.3%) squamous intra-epithelial lesions (p < 0.00008) which includes two out of the four women (50%) having HSIL, while only seven out of 104 (6.7%) of the subjects with normal (negative) Pap reports (p = 0.03) had infection of high-risk HPV. CONCLUSION: The results indicate that about 10% of women who show a negative Pap smear, but have inflammation are positive for high-risk HPV types 16/18 and about 15% harbor squamous intra-epithelial lesions. It is suggested that high-risk HPV detection can be utilized as an adjunct to routine cytology screening programs to identify 'high risk' women who have concurrently negative Pap smears but may harbor oncogenic HPV infection and/or more likely to develop CIN lesions.     

Effectiveness of screening for cervical cancer in an inpatient hospital setting

OBJECTIVE: To estimate the effectiveness of an inpatient, hospital-based cervical cancer screening program at a single institution. METHODS: Between January 1999 and December 2002, 1,117 women admitted to the Johns Hopkins Hospital underwent Papanicolaou (Pap) test screening during their hospital stay. In that time period, 111,933 women were screened at all of the combined Hopkins outpatient clinics. We compared rates of abnormal Pap tests in these cohorts (retrospective cohort study). Our main outcome measure was the prevalence of abnormal Pap tests among the screening population by age group, ethnicity, and insurance status compared between our outpatient and inpatient populations. RESULTS: The prevalence of abnormal Pap tests in the inpatient cohort was twice as high as that in the outpatient setting (15.5% versus 7%). The prevalence of high-grade squamous intraepithelial lesions (HSIL), the immediate precursor lesion to cervical cancer, was nearly 5-fold higher in the inpatient cohort compared with the outpatient cohort (3% versus 0.7%). In multivariable models, younger women had greater risk for all types of abnormal Pap tests, and black women had greater risk for HSIL. Previous abnormal Pap and human immunodeficiency virus-positive status were associated with all abnormal tests and with HSIL results. CONCLUSIONS: A hospital-based, inpatient Pap test program is an efficient strategy for targeting limited screening funds toward women at high risk of invasive cervical cancer. LEVEL OF EVIDENCE: II-2     

Comparison of HPV test versus conventional and automation-assisted Pap screening as potential screening tools for preventing cervical cancer

OBJECTIVE: To evaluate new techniques in primary cervical cancer screening programmes. DESIGN: Cross sectional pilot study. SETTING: Department of Obstetrics and Gynaecology, Helsinki University Hospital. POPULATION: Consecutive 2032 human papillomavirus (HPV) DNA and Pap smear samples were taken. Histological diagnoses were obtained from 460 patients. METHODS: We compared the validity of the high risk (HR) HPV DNA detection test to automation-assisted and conventional Pap smear screening. MAIN OUTCOME MEASURES: Specificity and sensitivity of screening methods. RESULTS: Twenty-three percent of women were HPV positive. Forty-five of 46 had high grade lesions and cancers were HR HPV DNA positive, whereas 72/93 of low grade and more severe lesions were HR HPV DNA positive. When histologically verified high grade lesions were observed, the relative sensitivity of HR Hybrid Capture 2 (HR HC2) test was 98% compared with conventional Pap smear and Papnet tests, which performed 54%versus 58%, 83%versus 86% and 93%versus 98% relative sensitivity respectively, using cytological diagnoses HSIL (high grade squamous intraepithelial lesion), LSIL (low grade squamous intraepithelial lesion) or ASCUS (atypical squamous cells of undetermined significance) as the cutoff. The specificity of HC2 test (77-79%) was comparable with the ASCUS+ (ASCUS and more severe) cytology (68-79%), but lower when compared with LSIL+ (91-95%) or especially HSIL+ (97-99%) Pap smear results. CONCLUSION: Pap smear, as a screening test, is very different from HPV DNA detecting test HR HC 2. If cutoff LSIL or more severe lesions is used, primary Pap smear is clearly more specific than HR HC2, but markedly less sensitive. Due to high relative sensitivity of the HPV, only very few histologically confirmed high grade lesions would be detected among HPV negatives using simultaneous cytology. On the other hand, using HPV DNA test alone would lead to multifold amounts of referrals for colposcopy. A posterior Pap smear assessment among HPV positives might be helpful in increasing sensitivity and specificity of screening and defining those who need an immediate referral or treatment. We plan to incorporate primary HR HPV DNA test with posterior Pap smear reading of HPV positives into our ongoing randomised prospective multiarm trial evaluating new techniques in organised screening for cervical cancer in Finland.