液基细胞学检测在宫颈癌筛查中的应用效果

目的探讨液基细胞学检测(TCT)在宫颈癌筛查中的应用效果。方法选取2015年6月至2016年12月间眉山市妇幼保健院收治的760例宫颈筛查患者,所有患者均行TCT检测,对于TCT阳性的患者行阴道镜检测,以病理诊断为金标准,观察分析TCT检测的准确度和特异度。结果760例患者中液基细胞学异常者159例(20.9%),其中不典型鳞状细胞(ASCUS)75例(9.9%),高度鳞状上皮内病变(HSIL)43例(5.7%),低度鳞状上皮内病变(LSIL)41例(5.4%)。159例患者阴道镜下宫颈活检术发现,宫颈上皮内瘤变(CIN)I患者73例(45.9%)。在75例ASCUS患者中,阴道镜检查CIN I 41例,CIN II 18例,TCT诊断符合率为78.7%;43例HSIL患者中,阴道镜检查CIN I14例,CIN II 18例,CIN III 6例,3例宫颈癌,符合率为95.3%;41例LSIL患者中,阴道镜检查CIN I18例,CIN II 13例,CIN III 3例,符合率为82.9%。结论 TCT检查在宫颈癌筛查中准确度较高,可为临床诊断提供一定的依据。     

8730例宫颈液基细胞学检查结果分析

[目的]评价利普液基细胞学（LPT）在宫颈癌变诊断中的应用价值。[方法]8730例利普液基细胞学样本采用TBS分类诊断,并与组织学活检结果对照。[结果]LPT细胞学阳性者723例,总检出率8.28%,其中意义不明的不典型鳞状细胞（ASC-US）345例（占3.95%）,不除外上皮内高度病变的不典型鳞状细胞（ASC-H）67例（占0.77%）,低度鳞状上皮内病变（LSIL）256例（占2.93%）,高度鳞状上皮内病变（HSIL）42例（占0.48%）,鳞状细胞癌（SCC）11例（占0.13%）,腺癌（AC）2例（占0.02%）,未检到意义不明的不典型腺细胞（AGUS）。HSIL活检阳性率和准确率分别为95.24%和85.72%,ASC-US活检阳性率33.16%。[结论]LPT对宫颈病变的检测有较高的敏感性和特异性。     

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。     

高危型人乳头瘤病毒HC2检测在宫颈上皮内瘤变筛查中的意义

目的:评估杂交捕获法Ⅱ(HC2)检测高危型人乳头瘤病毒(HPV)在子宫颈上皮内瘤变筛查中的价值.方法:回顾性分析2009年1月至2010年10月在我院妇科门诊进行宫颈薄层液基细胞学(LCT)检测和HPV-DNA 二联检查的700例患者,以及其中进行LCT、HPV-DNA 和阴道镜下宫颈多点活检三联检查的131例患者的临床资料,以组织病理活检结果作为金标准.结果:在二联检查的700例患者中,宫颈非典型性鳞状细胞(ASC)、低级别鳞状上皮内病变(LSIL)、高级别鳞状上皮内病变(HSIL)和鳞状细胞癌(SCC)组HPV阳性率分别为67%、93.3%、100%和100%,均高于未见上皮内病变或恶性病变组(NILM)43.6%(P＜0.05).在三联检查131例患者中,轻度宫颈上皮内瘤样病变(CINⅠ)、中度宫颈上皮内瘤样病变(CINⅡ)、重度宫颈上皮内瘤样病变(CINⅢ)和浸润癌组HPV阳性率分别为71.8%、92.9%、100%和100%,呈明显升高趋势,均高于病理结果正常组(无高危型HPV感染的湿疣,炎症与正常组织)57.7%.在HPV-DNA 和LCT结果均为阴性的228例,活检未发现阳性病例(高危型HPV感染的湿疣CINⅠ、CINⅡ、CINⅢ、浸润癌);HPV-DNA 阴性、LCT阳性的133例,活检发现2例阳性病例;HPV-DNA阳性、LCT阴性的176例,活检发现9例阳性病例;HPV-DNA阳性、LCT阳性的163例,活检发现75例阳性病例;结论:高危型HPV感染与宫颈癌前病变及宫颈癌密切相关.对于宫颈癌及其癌前病变的筛查及早期诊断,应以高危型HPV-DNA HC2检测辅助宫颈细胞学检查以提高检出率.     

利普液基细胞学(LPT)在宫颈病变诊断中的价值

目的:探讨利普超薄液基细胞学制片技术(Liquid-Prep Test, LPT)在宫颈病变中的应用价值.方法:7 000例患者接受LPT宫颈液基细胞学检查.部分结果异常者做阴道镜检查或宫颈多点活检进行组织病理学检查对照.结果:92例LPT宫颈细胞学检查与组织病理学对照结果显示:鳞状细胞癌(SCC)符合率最高,为100%(9/9),其次鳞状上皮内高度病变(HSIL)为90.91%(20/22),鳞状上皮内低度病变(LSIL)为72.41%(21/29).腺癌(AC)为100%(1/1).结论:LPT液基细胞学检查的敏感性高,它能准确地反映宫颈癌和癌前病变,是一种有效的宫颈癌的筛查手段.     

液基薄层细胞学在宫颈癌前病变和宫颈癌诊断中的价值

目的：探讨液基薄层细胞学检测在宫颈癌前疾病诊断中的临床价值。方法：采用第三代液基细胞学制片系统（LPT）制片,按TBS（The bethesda system）系统诊断为不能明确诊断意义的非典型鳞状细胞（ASCUS）以上的768例,其中低度病变（LSIL）以上184例;对有病理组织学诊断对照的139例进行了对比分析。结果：139例中细胞学诊断宫颈癌1例,宫颈高度病变（HSIL）13例,宫颈低度病变（LSIL）120例,非典型细胞不能除外高度病变（ASC—H）5例;与组织学结果对照,阳性符合率分别为癌100％,HSIL84．6％,LSIL70％。5例ASC—H中2例宫颈癌,1例宫颈上皮内瘤变（CIN）2级,1例CIN 1级-2级,1例湿疣。结论：液基细胞学在诊断宫颈癌前病变和宫颈癌方面,与组织学诊断结果有较高的符合率,因而具有较高的临床应用价值。     

TCT及阴道镜检查对宫颈病变诊断的临床价值

为了探讨液基薄层细胞学技术(thin prep cytologic test,TCT)及阴道镜检查对子宫颈病变的诊断价值,收集6 521例患者及健康体检者,进行TCT检测,TCT阳性者行阴道镜检查及活检.TCT异常者688例(10.55%),TCT和阴道镜对低度鳞状上皮内瘤变(LSIL)的检出率分别为63.96%(158/247)和70.04%(173/247),高度鳞状上皮内瘤变(HSIL)为73.03%(65/89)和84.27%(75/89),宫颈浸润癌(CC)为81.82%(27/33)和96.97%(32/33).初步研究结果提示,TCT筛查是诊断宫颈病变的重要方法,配合阴道镜下活检,能提高子宫颈癌前病变和宫颈早期浸润癌检出率,具有重要的临床意义.中华肿瘤防治杂志,2009,16(10):789-790     

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。     

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。     

宫颈液基细胞学筛查阴性及高危型人乳头瘤病毒筛查阳性患者临床病理特征分析

目的:分析宫颈液基细胞学(liquid-based thinlayer cytologic test,TCT)筛查阴性、高危型人乳头瘤病毒(high risk-human papillomavirus,HR-HPV)筛查阳性患者临床病理特征,探讨TCT阴性、HR-HPV阳性患者行宫颈病理活检的时机和意义。方法:选取2020年01月至2021年03月期间我院收治的TCT阴性且HR-HPV16和(或)18阳性或间隔1年后TCT阴性且15种HR-HPV的1种或多种持续阳性患者1 141例作为研究对象,进一步行电子阴道镜活检,分析TCT阴性、HR-HPV阳性状态下HPV分型及宫颈病变的临床病理和流行病学特征。结果:单一型HPV感染870例(76.2%),多重感染271例(23.8%);检出率最高的前5位HR-HPV亚型依次为HPV16、52、58、51、39。有491例接受阴道镜下组织活检,活检率43.0%(491/1 141),共检出LSIL 71例(14.5%)、HSIL 66例(13.4%)、宫颈癌6例(1.2%)。40岁以下年轻女性HSIL及以上病变的发生率更高,而在60岁及以上女性再次出现发病高峰,差异有统计学意义(χ2=9.950,P=0.041)。HPV16和(或)18亚型感染女性的活检率高于其余15种HR-HPV感染者(χ2=4.207,P=0.040),HPV16和(或)18感染女性的HSIL及宫颈癌的比率均高于其余15种HR-HPV感染者,差异有统计学意义(χ2=11.831,P=0.001; χ2=6.962,P=0.008)。多重感染女性的宫颈癌的比率高于单一感染者,差异有统计学意义(χ2=5.956,P=0.015);而其他宫颈组织病变程度(正常或宫颈炎、LSIL、HSIL)与HPV病毒感染种类数无显著相关(P均＞0.05)。结论:TCT检查存在较高的假阴性率,对于HPV16和(或)18感染患者首诊即应行阴道镜检查,而对于未行活检患者应重点加强随访管理。     

Performance of HPV DNA Testing with Hybrid Capture 2 in Triaging Women with Minor Cervical Cytologic Abnormalities (ASC-US/LSIL) in Northern Thailand

Background: Minor cervical cytologic abnormalities include atypical squamous cells of undeterminedsignificance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Approximately 10-20% of womenwith minor cytologic abnormalities have histologic high-grade squamous intraepithelial or worse lesions (HSIL+).In Thailand, women with minor cytologic abnormalities have a relatively high risk of cervical cancer, and referralfor colposcopy has been suggested. A triage test is useful in the selection of women at risk for histologic HSIL+ toreduce the colposcopy burden. The aim of this study was to assess the performance of high-risk HPV DNA test intriage of women with minor cytologic abnormalities in northern Thailand. Materials and Methods: All womenwith ASC-US/LSIL cytology who were referred to our colposcopy clinic from October 2010 to February 2014were included. HPV DNA testing was performed using Hybrid Capture 2 (HC2). All patients received colposcopicexamination. Accuracy values of HC2 in predicting the presence of histologic HSIL+ were calculated. Results:There were 238 women in this study (121 ASC-US and 117 LSIL). The HC2 positivity rate was significantlyhigher in the LSIL group than in ASC-US group (74.8% versus 41.0%, p<0.001). Histologic HSIL+ was detectedin 9 women (7.4%) in the ASC-US group and 16 women (13.7%) in the LSIL group (p=0.141). There was nohistologic HSIL+ detected among HC2-negative cases (sensitivity and negative predictive value of 100%). Theperformance of HC2 triage was highest among women aged >50 years with ASC-US cytology. An increase in thecut-off threshold for positive HC2 resulted in a substantial decrease of sensitivity and negative predictive value.Conclusions: HPV DNA testing with HC2 shows very high sensitivity and negative predictive value in triage ofwomen with minor cervical cytologic abnormalities in northern Thailand. An increase of the cut-off thresholdfor HC2 triage is not recommended in this region.     

Human papillomavirus testing for triage of women with low‐grade squamous intraepithelial lesions

Low‐grade squamous intraepithelial lesion (LSIL) is a common cytologic finding in cervical screening, yet only about 10–20% have significant histologic abnormalities and these are almost always positive for high‐risk human papillomavirus (hrHPV). This analysis aims to clarify the role of hrHPV DNA testing in the triage of women with LSIL cytology. In the ATHENA screening trial, we examined 1,084 cases of LSIL, of which 925 had an evaluable biopsy, to determine the extent to which hrHPV testing can identify those patients who have precursor lesions in need of immediate clinical referral and those who have changes more likely to regress spontaneously. Overall, 71.2% of LSIL cases were hrHPV positive, but the prevalence was age dependent, with only 56.1% in women ≥40 years. Among women with LSIL, 11.6% (107/925) had a cervical intraepithelial neoplasia grade 2 or worse (CIN2+) histologic diagnosis and, of these, only nine were hrHPV negative. For CIN3+, 91.7% (44/48) of women with LSIL were hrHPV positive. The negative predictive value of hrHPV testing for CIN3+ in LSIL was 100% for women aged ≥40 years. Women who were HPV16 positive had a higher positive predictive value for CIN2+ (25.4%) than those who were positive for 12 other pooled hrHPV types (11.5%). Testing for hrHPV in women with LSIL is effective in identifying high‐grade cervical lesions, thereby avoiding unnecessary referrals to colposcopy and potential over‐treatment of non‐progressive lesions, especially for women aged ≥40 years.     

宫颈病变液基细胞学筛查与组织病理学对照观察

目的　探讨液基薄层细胞学(ThinPrepCytologyTest, TCT)技术在妇科门诊人群宫颈病变筛查的准确性。方法　回顾性分析10 980例TCT,与组织学对比观察。结果　　TCTLSIL以上阳性率45. 7% ( 373 /817),组织学检查阳性率50. 1% ( 409 /817 ),两者统计学比较无显著性差异(P>0. 05 )。TCT诊断符合率LSIL75. 8% (191 /252),HSIL98. 1% (101 /103),SCC90. 9% (10 /11),AC85. 7% (6 /7)。鳞状上皮内病变诊断符合率HSIL与LSIL统计学比较有显著性差异(P<0. 01)。结论　液基细胞学检查是宫颈癌早期筛查的有效手段,加强制片技术及诊断质量控制对提高诊断的准确性有重要意义。     

P16/Ki-67 Dual Staining in Positive Human Papillomavirus DNA Testing for Predictive Diagnosis of Abnormal Cervical Lesions in Northeastern Thai Women

Objective: Cervical cancer screening can effectively reduce new cervical cancer cases, including in Thailand. The abnormal results are subsequently referred for colposcopy. To avoid unnecessary colposcopy, an efficient triage is still needed for validation. This study aimed to investigate the overall positivity of cytology-based screening, HPV detection, and p16/Ki-67 dual staining and evaluate different triage strategies for predictive diagnosis of abnormal cervical lesions in northeastern Thailand. Methods: Cervical cells were collected from 191 women who came for cervical screening in the gynecological outpatient department during March 2019-February 2020. Pap smear samples were classified into 6 groups including 17 atypical glandular cells (AGC), 21 atypical squamous cells of undetermined significance (ASC-US), 7 atypical squamous cells - cannot exclude HSIL (ASC-H), 26 low-grade squamous intraepithelial lesions (LSILs), 19 high-grade SILs (HSILs) and 101 no squamous intraepithelial lesion (noSIL). Polymerase chain reaction (PCR) was performed for HPV DNA detection. HPV genotyping was determined by reverse line blot hybridization. P16/Ki-67 dual staining was performed by using CINtec PLUS Cytology kit. Biopsies from abnormal screening were collected for surgical pathology classification. Results: High-risk HPV (HR-HPV) infection was 2.97%, 29.41%, 38.10%, 57.14%, 46.15% and 84.21% in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL cytology respectively. P16/ Ki-67 in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL was 0.99%, 5.88%, 9.52%, 42.86%, 26.92% and 63.16%, respectively (P-value < 0.001). Among p16/Ki-67 positive cases, 96.15% (25/26) were infected with HPV and 84.62% (22/26) were HR-HPV. The overall positivity of each and co-testing between cytology or HPV DNA testing or p16/Ki-67 dual staining was evaluated. In each cervical lesion, primary HPV DNA testing showed the highest sensitivity, but low specificity. The combined all HPV/HR-HPV with p16/Ki-67 detection increased the specificity of abnormal cervical lesions. Conclusion: P16/Ki-67 dual stain cytology in HPV-positive women performs well for diagnosis of abnormal cervical lesions and should be considered for management of HPV-positive women to avoid unnecessary colposcopy referrals.     

Risk factors for squamous intraepithelial lesions (SIL) of the cervix among women residing at the US-Mexico border

It is now well established that cervical cancer is caused by oncogenic human papillomavirus (HPV) infections that commonly infect women worldwide. What remains to be understood are the factors that contribute to cervical cancer in the presence of HPV infection. We conducted a case-control analysis of women recruited at the US-Mexico border to simultaneously evaluate factors associated with 3 cytologic outcomes: atypical squamous cells of undetermined significance or atypical glandular cells of undetermined significance (ASCUS/AGUS), low grade squamous intraepithelial lesions (LSIL) and high grade squamous intraepithelial lesions (HSIL). A cross-sectional binational study of 2059 women ages 15-79 years was conducted between 1997 and 1998. A significant difference in the distribution of cytologic categories by country was observed (3.0% vs. 0.7% HSIL among Mexican vs. US women, respectively). The only factors independently associated with all 3 cytologic outcomes were HPV infection and viral load. A linear increase in risk with increasing viral load was observed for each of the 3 outcome variables, with the strength of this association increasing with cytology abnormality. In addition to HPV infection, parity and Mexico as a country of residence appear to be associated with LSIL and HSIL, respectively. Factors associated with cytologic outcomes in analyses limited to women with HPV infection were similar to results obtained in models where HPV infection was included as a covariate. Future work is needed to evaluate the predictive value of HPV viral load utilizing more specific and quantitative measures.     

Pathology correlates of a Papanicolaou diagnosis of low‐grade squamous intraepithelial lesion,cannot exclude high‐grade squamous intraepithelial lesion

BACKGROUND.

The objective of this study was to compare findings after a cytologic report of low‐grade squamous intraepithelial lesion, cannot exclude high‐grade squamous intraepithelial lesion (LSIL‐H) with findings after a report of low‐grade squamous intraepithelial lesion (LSIL).

METHODS.

A review of patient records revealed that 312 women had cytologic findings of LSIL‐H, and 324 consecutive women in a comparison group had cytologic findings of LSIL during 2005. Findings over 6 months after diagnosis were retrieved and analyzed using chi‐square tests, Fisher exact tests, and independent group t tests.

RESULTS.

Histology was available for 194 of 312 women (64%) with LSIL‐H and for 184 of 324 women (57%) with LSIL. Of these, 47 of 194 women (24%) with LSIL‐H had grade 2 cervical intraepithelial neoplasia or greater (CIN2+) versus 13 of 184 women (7%) with LSIL (P < .0001). No cancers were identified. High‐grade SIL cytology was reported in 2 of 105 women who had LSIL (2%) and in 4 of 93 women who had LSIL‐H (4%). Women with LSIL‐H who were positive for CIN2+ were younger than those without CIN2+ (25 years vs 30 years; P = .0067)

CONCLUSIONS.

Clinicians whose laboratories report LSIL‐H should manage women who have LSIL‐H with colposcopy, whereas only serial cytologic surveillance is required after a report of LSIL. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

Prevalence of High Grade Squamous Intraepithelial Lesion (HSIL) and Invasive Cervical Cancer in Patients with Low Grade Squamous Intraepithelial Lesion (LSIL) at Cervical Pap Smear

Objective: To assess the prevalence and factors associated with a histologic diagnosis of high grade squamous intraepithelial lesion (HSIL) and invasive cervical cancer in patients with low grade squamous intraepithelial lesion (LSIL) cervical pap smear findings. Methods: Medical records (including cytology reports, colposcopic impression, and pathologic results from cervical biopsy, endocervical curetting, cervical conization or hysterectomy) of 226 women with LSIL from conventional cervical pap smears during January 2001 to December 2005, who subsequently underwent colposcopic evaluation at our institution, were reviewed. Results: Mean age of the patients was 39.0 years. The incidences of LSIL, HSIL, microinvasive cervical cancer were 58.8%, 15.0%, 1.3% respectively. No associations were found between age, parity, contraception, anti-HIV or menstrual status and the detection of HSIL/invasive cervical cancer. Conclusion: Approximately 16.3 % of LSIL pap smear cases turn out to be HSIL or invasive cervical cancer from histologic diagnosis.     

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: diagnostic performance, human papillomavirus testing, and follow-up results

BACKGROUND: Current guidelines recommend colposcopy rather than high-risk human papillomavirus (HPV) testing for the evaluation of abnormal cervical cytology interpreted as "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" (ASC-H) based on data from the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion (ASCUS/LSIL) Triage Study (ALTS), which indicated that ASC-H had a significantly greater frequency of high-risk HPV positivity and underlying high-grade squamous intraepithelial lesions (HSIL) compared with ASCUS. The cytologic interpretations in the ALTS were expert consensus diagnoses rather than routine, single-pathologist readings. METHODS: The authors conducted a comparative analysis of Hybrid Capture 2 high-risk HPV positivity and frequency of histologically diagnosed HSIL for ASC-H and ASCUS to evaluate the performance of ASC-H as a cytologic interpretation subcategory and the potential utility of HPV testing for colposcopy triage of ASC-H in routine practice. RESULTS: Sixty-four of 96 patients with ASC-H (66.7%) were HPV-positive compared with 484 of 1079 patients with ASCUS (44.9%). Among the patients who had histologic follow-up, HSIL was identified in 18 of 45 patients (40.0%) with HPV-positive ASC-H compared with 27 of 266 patients (10.2%) with HPV-positive ASCUS (P < 0.0001) and 1 of 22 patients (4.5%) with HPV-negative ASC-H (P = 0.003); the latter result was similar to the finding of HSIL in 5 of 85 patients (5.9%) with HPV-negative ASCUS. The frequency of HPV-positive ASC-H in the current study (67%) was lower than that obtained in the ALTS for ASC-H (86%) but higher than that for ASCUS in both this study (45%) and in the ALTS (51% for all ASC; 63% for ASCUS, equivocal for LSIL). Underlying HSIL was detected in a similar percentage of patients with HPV-positive ASC-H in this study and in the ALTS (41%). CONCLUSIONS: The greater frequency of HPV positivity and the significantly increased risk of underlying HSIL for ASC-H compared with ASCUS indicated that ASC-H category utilization and performance are appropriate in this routine clinical practice setting. The lower frequency of HPV positivity for ASC-H compared with the ALTS data and the similar low risk of HSIL in HPV-negative ASC-H and HPV-negative ASCUS indicate that HPV testing for triage of ASC-H in routine practice has the potential to reduce the number of women who are referred for colposcopy without an increased risk of failure to detect HSIL among HPV-negative women, similar to its triage role for ASCUS.     

Combined use of cytology,p16 immunostaining and genotyping for triage of women positive for high-risk human papillomavirus at primary screening

Human papillomavirus (HPV) testing is very sensitive for primary cervical screening but has low specificity. Triage tests that improve specificity but maintain high sensitivity are needed. Women enrolled in the experimental arm of Phase 2 of the New Technologies for Cervical Cancer randomized controlled cervical screening trial were tested for high-risk HPV (hrHPV) and referred to colposcopy if positive. hrHPV-positive women also had HPV genotyping (by polymerase chain reaction with GP5+/GP6+ primers and reverse line blotting), immunostaining for p16 overexpression and cytology. We computed sensitivity, specificity and positive predictive value (PPV) for different combinations of tests and determined potential hierarchical ordering of triage tests. A number of 1,091 HPV-positive women had valid tests for cytology, p16 and genotyping. Ninety-two of them had cervical intraepithelial neoplasia grade 2+ (CIN2+) histology and 40 of them had CIN grade 3+ (CIN3+) histology. The PPV for CIN2+ was >10% in hrHPV-positive women with positive high-grade squamous intraepithelial lesion (61.3%), positive low-grade squamous intraepithelial lesion (LSIL+) (18.3%) and positive atypical squamous cells of undetermined significance (14.8%) cytology, p16 positive (16.7%) and, hierarchically, for infections by HPV33, 16, 35, 59, 31 and 52 (in decreasing order). Referral of women positive for either p16 or LSIL+ cytology had 97.8% sensitivity for CIN2+ and women negative for both of these had a 3-year CIN3+ risk of 0.2%. Similar results were seen for women being either p16 or HPV16/33 positive. hrHPV-positive women who were negative for p16 and cytology (LSIL threshold) had a very low CIN3+ rate in the following 3 years. Recalling them after that interval and referring those positive for either test to immediate colposcopy seem to be an efficient triage strategy. The same applies to p16 and HPV16.