高危型人乳头状瘤病毒检测在不除外高度鳞状上皮内病变的不典型鳞状上皮细胞中的意义

目的 探讨高危型人乳头状瘤病毒(HR-HPV)的检测在宫颈细胞学不除外高度鳞状上皮内病变的不典型鳞状上皮细胞(ASC-H)中的意义.方法 对45例诊断为ASC-H的患者用杂交捕获二代(HC-Ⅱ)方法检测HR-HPV DNA含量,并进行阴道镜检查及活检,分析其结果之间的关系.结果 45例ASC-H的活检结果为宫颈鳞状上皮内病变(SIL)33例(73.3%);45例ASC-H中36例HR-HPV阳性,其中高度鳞状上皮内病变(HSIL)及以上病变者19例(52.8%);9例HR-HPV阴性病例中,没有HSIL及以上病变;HR-HPV对ASC-H患者HSIL的敏感性及阴性预测值均为100%.结论 ASC-H高度提示宫颈病变的存在;HR-HPV可以作为ASC-H患者是否需要立即阴道镜检查的一个预测指标,HR-HPV阳性者应立即阴道镜检查及活检,HR-HPV阴性是HSIL阴性的一个预测指标.     

宫颈液基薄层细胞学筛查中非典型鳞状细胞研究进展

非典型鳞状细胞(atypical squamous cells，ASC)自1943年被首次提出，历经1988，1991和2001年TBS (the Bethesda System)三版修订，非典型鳞状细胞被分为意义不明确的不典型鳞状细胞(ASC of undetermined significance，ASC-US)和不除外高度上皮内病变的不典型鳞状细胞[ASC cannot exclude high-grade squamous intraepithelial lesion (HSIL)，又称为ASC-H]，这两个术语已得到临床实践证实，用其作为诊断分类明显提高了宫颈巴氏细胞学临床使用性。诊断为ASC-US和ASC-H的患者行高危型人乳头状瘤病毒(high-risk types of human papillomavirus，HR HPV)检测后分组管理，使后续的处理及治疗更加人性化，提高了宫颈液基薄层细胞学筛查的可靠性，降低了人为的过度治疗，使宫颈细胞学筛查更具科学性、可行性。     

P16INK4A和人乳头状瘤病毒检测对宫颈上皮高度病变的预测意义

目的 探讨在液基细胞学(TCT)未明确意义的不典型鳞状上皮细胞(ASCUS)中,P16INK4A免疫细胞化学染色和高危型人乳头状瘤(HR-HPV)检测对宫颈上皮内高度病变(HSIL)的预测意义.方法 应用免疫细胞化学方法检测P16INK4A在89例液基细胞学不典型鳞状上皮细胞(ASC-US 55例和ASC-H 34例)中的表达,用第二代杂交捕获法(HC-2)检测每一患者的13种HR-HPV DNA,并同组织病理诊断结果比较.结果 在89例ASCUS中,组织病理证实:HSIL(CIN2/3)22例,宫颈癌2例.占26.97%(24/89).P16INK4A免疫细胞化学染色阳性26例中,组织病理证实:CIN2/3 20例,宫颈癌2例,CIN1和宫颈炎4例;HC-2HR-HPV DNA检测阳性64例,组织病理证实:CIN2/3 21例,宫颈癌2例,CIN1和宫颈炎41例;差异有统计学意义(P<0.01).P16INK4A免疫细胞化学染色对宫颈鳞状上皮内高度病变(HSIL)的阳性预测值(PPV)和特异性(Sp)分别为84.62%和93.85%,明显高于HC-2 HR-HPV DNA检测的PPV 35.94%和Sp 36.92%.结论 在TCT-ASCUS中,P16INK4A特异免疫染色比HG2 HR-HPVDNA检测能够更可靠地鉴别宫颈良、恶性疾病,二者联合检测将会为病人提供一种更有效、更合理的处理方案.     

9012例子宫颈液基细胞学诊断结果分析

目的探讨液基薄层细胞(TCT)检查在宫颈癌及癌前病变筛查中的应用价值。方法回顾分析开县人民医院9 012例宫颈液基细胞学检测结果和伯塞斯达系统(TBS)分类系统结果,其中12例ASC-US、10例ASC-H、35例低度鳞状上皮内病变(LSIL)、72例高度鳞状上皮内病变(HSIL)、2例鳞状上皮细胞癌(SCC)和6例腺细胞异常做阴道镜下病理活检,对细胞学异常结果与阴道镜下活组织检查病理诊断结果进行比较。结果 9 012例液基细胞学检测中,筛查出非典型鳞状细胞(ASC-US)以上病例285例,阳性率3.2%。液基细胞学检测与阴道镜下病理活检结果的符合率为91.24%。结论 TCT制片技术和TBS报告能较全面反映宫颈病变的情况,通过定期正规的筛查,能早期发现宫颈癌及癌前病变,从而早期治疗,阻止病变升级是预防宫颈癌的关键。     

高危型人乳头状瘤病毒和宫颈细胞学联合检测在诊断宫颈病变中的临床价值

目的 探讨高危型人乳头状瘤病毒(hish-risk human papillomavirus,HR-HPV)和宫颈细胞学联合检测在诊断宫颈病变中的临床价值.方法 对2004年10月至2006年12月北京大学第一医院就诊的患者进行HR-HPV检测和宫颈细胞学检查,对一项或两项结果异常者均行阴道镜下宫颈活检,并以宫颈活检结果为金标准,比较HR-HPV检测、宫颈细胞学检查、HR-HPV和宫颈细胞学联合检测对宫颈病变的诊断价值.结果 HR-HPV检测、宫颈细胞学检查及HR-HPV检测联合宫颈细胞学检查对诊断宫颈病变有不同价值.HR-HPV检测筛查CINⅡ、CINⅢ的敏感度、特异度、阳性预测值和阴性预测值分别为94.83%、31.06%、55.22%、87.02%,宫颈细胞学筛查CINⅡ、CINⅢ的敏感度、特异度、阳性预测值和阴性预测值分别为92.10%、31.06%、54.50%、81.43%,HR-HPV和宫颈细胞学联合检测筛查CINⅡ、CINⅢ的敏感度、特异度、阳性预测值和阴性预测值分别为99.65%、18.55%、61.46%、97.62%.结论 采用HR-HPV和宫颈细胞学联合检测可提高宫颈病变的检出率,并可指导临床医生对宫颈病变的治疗.     

HPV-DNA分型检测在不同类型的ASC中的意义

目的 了解非典型鳞状细胞(ASC)的两种不同亚型--ASC-US和ASC-H患者临床结局的差异,以及HPV-DNA分型检测在两种不同亚型中的意义.方法 对2005年1月至2007年12月宫颈脱落细胞学判读为ASC的1256例(其中580例同时行HPV-DNA分型检测)行阴道镜及活检,并对上述资料进行分析和总结.结果 在1256例ASC中ASC-US和ASC-H分别占90.1%和9.9%,经阴道镜和宫颈活检病理诊断CIN2及以上的分别为8.5%和24.2%(P=0.000).在ASC-US组HPV高危亚型的感染率为67.2%,不同的HPV-DNA检测结果与阴道镜以及病理检查结果间相比差异有统计学意义(P=0.000).在ASC.H组HPV高危亚型的感染率为47.3%,不同的HPV-DNA检测结果与阴道镜以及病理检查结果间相比差异无统计学意义(P=0.054).结论 ASC的两种不同亚型患者的临床结局不同,应区别对待.HPV-DNA分型检测在ASC-US患者分层处理中有意义,但对于ASC-H患者建议全部行阴道镜检查.     

人乳头状瘤病毒分型检测在宫颈细胞学诊断为ASCUS分层处理中的意义

目的 探讨人乳头状瘤病毒(human papillomavirus,HPV)分型检测在宫颈细胞学诊断为不典型鳞状细胞意义不明确(atypical squamous cell of undetermined significance.ASCUS)分层处理中的意义.方法 对184例宫颈细胞学诊断为ASCUS的患者,分别进行HPV检测和阴道镜下宫颈组织活检.结果 184例宫颈细胞学诊断为ASCUS的患者中,经组织病理学证实炎症112例(60.87%),CIN Ⅰ级33例(17.93%),CIN Ⅱ级17例(9.24%),CIN Ⅲ级8例(4.35%),宫颈鳞癌4例(2.17%),宫颈湿疣10例(5.43%).其中124例经检测呈高危型HPV(high-risk types HPV,HR-HPV)阳性,阳性率为67.39%(124/184),随后经病理学证实炎症66例(53.23%),CIN Ⅰ级22例(17.74%),CIN Ⅱ级16例(12.90%),CIN Ⅲ级8例(6.45%),宫颈鳞癌4例(3.23%),宫颈湿疣8例(6.45%).HPV阳性组CIN以上病变检出率明显高于HPV阴性组(P<0.003).结论对宫颈细胞学诊断为ASCUS的患者,建议作HPV检测,若HR-HPV阳性,则需进一步阴道镜下宫颈活检;若HPV阴性,酌情处理.     

细胞块在宫颈液基细胞学中的应用

目的探讨细胞块(cell block,CB)在宫颈液基细胞学(liquid-based preparation,LBP)中的应用价值。方法选择LBP阳性标本285例,其中高危HPV 16型45例、HPV 18型58例,HPV高危其他型(31、33、35、39、45、51、52、56、58、59、66、68型)182例,同时制作成CB并行阴道镜活检247例,最终均以组织学诊断为金标准。结果对于非典型鳞状上皮细胞(atypical squamous cells,ASC),应用LBP与LBP+CB检测同时阳性的组织学阳性符合率差异有显著性(72.3%±2.3%vs 83.2%±1.1%,P0.01),其中诊断为非典型鳞状上皮细胞-意义不明的(atypical squamous cells of undetermined significance,ASC-US)标本中,LBP与LBP+CB同时阳性的组织学阳性符合率分别为66.28%(57/86)、78.85%(41/52);诊断为非典型鳞状上皮细胞-不除外高级别鳞状上皮内病变(atypical squamous cells,cannot exclude hsil,ASC-H)标本中,LBP与LBP+CB同时阳性的组织学阳性符合率分别为82.98%(39/47)、89.74%(35/39)。对于低级别鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL),LBP+CB同时阳性的组织学阳性符合率比LBP高,但差异无统计学意义(P0.05);而对≥高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)和非典型腺细胞(atypical glandular cells,AGC),LBP与LBP+CB同时阳性的组织学阳性符合率一致;在62例LBP诊断LSIL标本中,CB诊断分别为无上皮内病变或恶性病变(negative for squamous intraepithelial lesions or malignancy,NILM)2例、ASC-US 7例、ASC-H 10例、LSIL 33例、HSIL 10例;对于50例LBP诊断HSIL标本中,CB诊断分别为ASC-US 2例、ASC-H 11例、LSIL 5例、HSIL 30例、鳞状细胞癌(squamous cell carcinoma,SCC)2例。HSIL、NILM、LSIL组中p16表达差异有显著性(P0.05)。另外,p16在HSIL组中的阳性表达明显高于LSIL组。结论 CB在LBP中的应用,可以提高宫颈癌筛查的组织学阳性符合率,也可作为临床高度怀疑有病变或高危HPV而LBP未见阳性的一种补充,值得在临床细胞病理学中推广。     

ASCUS患者发生宫颈高级别病变高危因素分析

探讨不能明确意义的非典型鳞状细胞患者发生CINⅡ 及其以上宫颈病变的影响因素。方法 通过完善设计的调查量表对我院门诊就诊行宫颈液基细胞学检查（TCT）为ASCUS的236例患者进行回顾性资料收集,同时行人乳头瘤状病毒（HPV）基因型检测,和阴道镜检查+宫颈活检,对相关危险因素进行单因素和多因素分析。结果 236例ASCUS病变中,病理证实CIN共68例（28.81%）,其中CINⅡ及以上检出36例,占总病例数的15.25%。236例ASCUS病例中,高危型HPV阳性率为55.51%,高危型HPV阳性及高危型HPV阴性组CINⅡ及以上病变检出率分别为25.19%、2.86%,差异有统计学意义（P＜0.05）。高危型HPV检测CINⅡ及其以上的敏感性达91.67%,阴性预测值达97.14%。单因素分析中年龄、初次性生活年龄、流产次数、HR-HPV与CINⅡ及其以上密切相关。Logistic多因素回归分析的结果表明初次性生活年龄、流产次数、HR-HPV是宫颈CINⅡ及其以上的高危因素。结论 高危型HPV检测是ASCUS患者分流的重要指标,尤其是年龄在30~50岁。初次性生活年龄≤20岁、流产次数＞2次、HR-HPV是ASCUS患者发生宫颈高度病变的独立的高危因素。     

细胞免疫化学p16/Ki-67双染预测子宫颈上皮内高级别瘤变

目的 探讨细胞免疫化学p16/Ki-67双染预测子宫颈上皮内高级别瘤变及其意义。方法 随机收集行细胞学检查标本123例,其中不明意义的非典型鳞状上皮细胞(atypical squamous cell of undetermined significance,ASC-US)及以上病例(合计103例)同时行高危人乳头瘤病毒(high risk-human papillomavirus,HR-HPV)检测且具有活检结果,20例液基细胞学检查未见恶性细胞和上皮内病变细胞(negative for intraepithelial lesion or malignancy,NILM),通过细胞免疫化学双染检测p16/Ki-67结果。结果 20例液基细胞学NLIM的标本中p16/Ki-67双染结果均阴性,ASC-US病例中预测CIN2+的敏感性66.67%、特异性95.92%、阳性预测值50.00%、阴性预测值97.92%,低级别鳞状上皮内病变(low-grade squamous intraepithelial lesions,LSIL)病例中预测CIN2+的敏感性91.67%、特异性95.00%、阳性预测值91.67%、阴性预测值95.00%,高级别鳞状上皮内病变(high-grade squamous intraepithelial lesions,HSIL)病例中预测CIN2+的敏感性92.86%、特异性0、阳性预测值92.86%、阴性预测值0;ASC-US及以上病例预测CIN2+的敏感性89.66%、特异性94.28%、阳性预测值86.67%、阴性预测值95.65%。结论 HR-HPV阳性的ASC-US和LSIL病例中进行p16/Ki-67双染检测,可以明显提高CIN2+检出的预测值,细胞免疫化学p16/Ki-67双染有望成为HPV筛查的有效辅助方法。     

Dual immunostaining of cervical cytology specimens with atypical squamous cells for p16/Ki-67 does not exclude the existence of a high-grade squamous intraepithelial lesion

This study was conducted to evaluate the accuracy of p16/Ki-67 dual immunostaining compared to high-risk human papillomavirus (HR-HPV) DNA testing for cervical intraepithelial neoplasia (CIN) in women with atypical squamous cells, cytology not excluding high-grade squamous intraepithelial lesion (ASC-H). Data were collected from 73 patients diagnosed to have ASC-H on a Pap smear who were HPV genotyped and had histological examination of a cervical biopsy. The CINtec®PLUS kit was used on residual liquid-based material, and the immunoreactivity of dual-stained cells was graded according to the number as follows: G1 (1–5 positive cells), G2 (6–10), G3 (11–20), and G4 (> 20). Accuracy was evaluated based on the histological examination of colposcopy-guided biopsy or cervical conization on follow-up. Of the 70 patients with available data, positive p16/Ki-67 was associated with histological severity as follows: 15 % in negative histology, 67 % in CIN 1, 90 % in CIN 2, and 100 % in CIN 3. The average grade of positive p16/Ki-67 staining also increased from 0.2 in histologically negative cases to 1.2 in CIN 1, 2.4 in CIN 2, and 2.9 in CIN 3 (p?<?0.01). For patients with CIN 2 or higher, p16/Ki-67 had a sensitivity of 94.6 % and a specificity of 75.8 %, while HR-HPV testing showed a sensitivity of 67.6 % and a specificity of 66.7 %. p16/Ki-67 immunostaining demonstrated better accuracy than HR-HPV for detecting CIN 2 or higher in patients with ASC-H cytology. Given the higher concordance with histological diagnosis, the grading system of positive p16/Ki-67 can be a useful adjunct for predicting high-grade lesions in clinical practice.     

"Low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion" is a distinct cytologic category: histologic outcomes and HPV prevalence

We examined the histologic outcomes and prevalence of high-risk human papillomavirus (HR-HPV) in women with liquid-based Papanicolaou (Pap) tests interpreted as "low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion" (LSIL-H) compared with the 2001 Bethesda System (TBS 2001) cytologic categories of LSIL, high-grade SIL (HSIL), and atypical squamous cells, cannot exclude HSIL (ASC-H). A computer search identified 426 LSIL, 86 ASC-H, 81 LSIL-H, and 110 HSIL cytologic interpretations during a 1-year period, each with up to 2 years of histologic follow-up. The risk of histologic cervical intraepithelial neoplasia (CIN) 2 or worse (CIN 2+) associated with LSIL-H (32/81 [40%]) was intermediate between LSIL (46/426 [10.8%]) and HSIL (72/110 [65.5%]), but not significantly different from ASC-H (23/86 [27%]). However, LSIL-H was more frequently associated with a definitive histologic diagnosis of any CIN (CIN 1+) than ASC-H (53/81 [65%] vs 35/86 [41%]). Moreover, the prevalence of HR-HPV was significantly greater in patients with LSIL-H than in patients with ASC-H (15/15 [100%] vs 43/73 [59%]). The histologic outcomes and HR-HPV prevalence associated with LSIL-H differ significantly from the established categories of TBS 2001 and provide evidence to support the recognition of LSIL-H as a distinct cytologic category.     

Correlation of histopathologic/cytologic follow-up findings with vaginal ASC-US and ASC-H Papanicolaou test and HPV test results

Current American Society of Colposcopy and Cervical Pathology recommendations about human papillomavirus (HPV) triage and further management for atypical squamous cells are pertinent to cervical Papanicolaou (Pap) tests. There are limited data on HPV detection in vaginal liquid-based cytology (LBC) specimens. The aims of this study were to determine whether adjunctive high-risk (HR)-HPV testing is useful for disease risk assessment in women with vaginal atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells, cannot exclude HSIL (ASC-H) Pap results. We identified 1,125 ASC-US and 36 ASC-H vaginal Pap results with HR-HPV testing. Of the cases, 244 (21.7%) ASC-US and 21 (58%) ASC-H were HR-HPV+. Among ASC-US HR-HPV+ cases, 47.8% had a squamous intraepithelial lesion (SIL) compared with 4.7% of HR-HPV- cases. Among ASC-H HR-HPV+ cases, 75% (12/16) had SIL compared with 31% (4/13) in HR-HPV- cases. Our results indicate that HPV triage testing is a reasonable and cost-effective approach for women with ASC-US vaginal Pap results and also a useful option for women with ASC-H vaginal Pap results.     

Reflex high-risk human papilloma virus DNA test is useful in the triage of women with atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion

This study is aimed to investigate the role of reflex high-risk human papilloma virus (HPV) DNA testing as an alternative triage method to colposcopy for women with atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on Papanicolaou (Pap) tests. Reflex HPV DNA testing using Hybrid Capture II method was carried out on 88 women with ASC-H diagnosed by Thin Prep Pap test. Correlation with follow-up biopsies was available on 42 of these patients. The reflex HPV DNA test showed an overall positive rate of 67% and negative rate of 33% in 88 patients with ASC-H. Using age 30 as the cut off point, the positive rate had increased to 83.3% (35/42) in patients 30 yr or younger, while the positive rate for patients older than 30 yr had decreased to 52.2% (24/46). Follow-up colposcopic biopsy results were available in 35 of 59 HPV-positive women, which revealed 15 (43%) high-grade squamous intraepithelial lesions (HSIL), 12 low-grade squamous intraepithelial lesions (LSIL), and 8 negative for dysplasia. In 7 HPV-negative patients, the follow-up biopsies showed no evidence of HSIL or LSIL. Correlation between clinical risk factors and the HPV results demonstrated no significant differences in HPV positivity between the high-risk and low-risk patients. The high sensitivity (100%) and negative predictive rate (100%) in detecting HSIL in our study provide strong evidence that, instead of automatic referral to colposcopy, reflex HPV DNA testing may be used as an alternative triage method for women diagnosed with ASC-H on Thin Prep Pap test, especially for women older than 30 yr of age.     

Atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion: the practice experience of a hospital-based reference laboratory with this new Bethesda system diagnostic category

The 2001 Bethesda System diagnostic category of atypical squamous cells cannot exclude a high grade squamous intraepithelial lesion (ASC-H) was developed and implemented after many studies that proved its clinical relevance. In this study, we describe the practice experience of a hospital-based reference laboratory with this new diagnostic category. The anatomic pathology computer database was searched, and 414 Papanicolaou (Pap) smears signed out as ASC-H were discovered among 60,390 Pap smear accessions over a 17-month period of time. One hundred four cases had corresponding tissue specimens. Slides from all Pap smears and tissue specimens were reviewed, and five Pap smears were reclassified, leaving 99 study cases. In our laboratory, 88.9% of the study cases had either low or high grade dysplasia diagnosed on subsequent tissue specimens. The positive predictive value of ASC-H for histologically proven high-grade squamous intraepithelial lesions (HSIL's) was 40.4%. Of those having human papillomavirus (HPV) hybrid capture II testing, high-risk HPV types were detected in 73.9% of cases. The majority of study cases had less than 25 atypical cells. In two hysterectomy cases and three loop electrosurgical excession procedure (LEEP) conization cases, high-grade dysplasia was present as a single microscopic focus, suggesting that the paucity of atypical cells in ASC-H Pap smears may be secondary to small lesion sampling. Thirteen study patients were postmenopausal and 30.8% had low-grade dysplasia, and of these, 46.2% had high-grade dysplasia on subsequent tissue specimens. In conclusion, our practice experience with ASC-H is similar to that reported in the literature before the 2001 Bethesda System.     

Atypical squamous cells,cannot exclude high grade intraepithelial lesion (ASC‐H): Does HPV matter?

The role of human papillomavirus (HPV) in cases diagnosed as atypical squamous cells, cannot exclude high squamous grade intraepithelial lesion (ASC-H) in cervical specimens is not well established. The objective of this study is to evaluate the role of HPV status in cases of ASC-H in a major cancer center. One hundred thirty-two patients with a diagnosis of ASC-H were identified over a 4-yr period in our institution. Forty-four of 132 cases were evaluated for high-risk HPV and had biopsy follow-up. The positive predictive value (PPV) of ASC-H for high-grade squamous intraepithelial lesions overall was 32% while PPV of ASC-H with associated HR HPV was 42%. This increase was statistically significant with P = 0.003 and suggest that HPV testing might be useful to increase the PPV of ASC-H.     

Immunostaining of p16INK4a/Ki-67 and L1 Capsid Protein on Liquid-based Cytology Specimens Obtained from ASC-H and LSIL-H Cases

Background: Atypical squamous cell cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and low-grade intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion (LSIL-H) are ambiguous diagnostic entities for the prediction of high-grade cervical lesion. Objective and reproducible tests for predicting high-grade cervical lesions are needed to reduce unnecessary colposcopic referrals or follow-ups.Objective: We aimed to identify an adequate set of adjunctive markers to predict cervical intraepithelial neoplasia grade 2+ (CIN2+) in residual liquid-based cytology specimens (LBCS).Methods: We conducted p16 ^INK4a/Ki-67 and L1 capsid protein immunostaining and human papillomavirus (HPV) DNA typing on 56 LBCS diagnosed with ASC-H or LSIL-H, all of which were subjected to histologic confirmation or follow-up cytologic examination.Results: Positivity for p16 ^INK4a/Ki-67 was associated with a histology of CIN2+ (P=0.047) and CIN3+ (P=0.002). Negativity for L1 capsid protein was associated with CIN2+ confirmed at follow-up (P=0.02).Positivity for high-risk HPV (HR-HPV) was associated with CIN2+ confirmed at follow-up (P=0.036) and a histology of CIN2+ (P=0.037). The sensitivity, specificity, positive predictive value, and negative predictive value for predicting follow-up CIN2+ were 76.2%, 51.4%, 48.5%, and 78.3%, respectively, for p16 ^INK4a/Ki-67 immunostaining; 95.2%, 34.3%, 46.5%, and 92.3%, respectively, for L1 capsid protein; and 66.7%, 67.7%, 54.5%, and 77.8%, respectively, for HR-HPV. The classification and regression tree analysis showed that the combined results of p16 ^INK4a/Ki-67 andL1 capsid protein immunostaining and the HR-HPV test, conducted sequentially, correctly classified 81.8% of samples (27/33)in the prediction of a histology of CIN2 + in ASC-H or LSIL-H. For determination of the histology of cervical intraepithelial neoplasia grade 3+ (CIN3+)in ASC-H or LSIL-H, we found that the combined results of p16 ^INK4a/Ki-67 and L1 capsid protein immunostaining correctly classified 78.8% (26/33) of samples.Conclusions: p16^INK4a/Ki-67 and L1 capsid protein immunostaining and HR-HPV testing of residual LBCS diagnosed with ASC-H or LSIL-H are useful objective biomarkers for predicting CIN2+. Immunostaining for p16^INK4a/Ki-67 and L1 capsid protein are sufficient to predict CIN3+.     

The value of duplicate slides on atypical squamous cells, cannot exclude high-grade intraepithelial lesion

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) category was added to the 2001 Bethesda System. ASC-H accounts for a small percentage (0.2-0.6%) of abnormal Pap smears and includes heterogenous group of lesions. There are more high-grade cervical lesions (30-50%) in ASC-H than ASC-US (10-15%). An accurate Pap diagnosis is crucial for appropriate patient follow-up and treatment. A total of 43 consecutive ASC-H cases were collected from October 2007 to March 2008, and all duplicate and the original slides were reviewed blindly at the end of the study. On review of the duplicate Pap slides, 18 cases had diagnostic SIL cells (15 HSIL, 2 LSIL with ASC-H, and 1 LSIL). The duplicate slides could have potentially changed 18 (41.9%) ASC-H diagnoses to a more definitive SIL diagnosis. On review of the original Pap slides, 8 of these 18 cases also had HSIL cells. Twenty-one follow-up cervical biopsies (21/43, 48.8%) showed 12 CIN 2/3, 4 CIN 1, 1 VAIN 1, 2 cervical polyps, 1 negative for dysplasia, and 1 insufficient for diagnosis. The CIN 2/3 rate was 57.1% (12/21) based on the original ASC-H Pap diagnosis. The CIN 2/3 rates were 80% (8/10) with SIL cells on duplicate slides and 36.4% (4/11) without SIL cases on duplicate slides. Our study suggested that duplicate slides were very useful for further classification of ASC-H, but other ancillary tests might be necessary for some cases. We propose a systematic approach using combined duplicate slides and reflex HPV testing to further classify ASC-H.     

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion. A follow-up study of conventional and liquid-based preparations in a high-risk population

We compared the histologic follow-up of 368 smears or slides with an interpretation of "atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion" (ASC-H) based on conventional and liquid-based preparations and age groups in a high-risk population. Patients with an ASC-H interpretation were 17 to 87 years old (mean, 36.8 years). The specimens were 52 liquid-based preparations and 316 conventional smears. For 218 cases (59.2%), including 28 liquid-based preparations (65%) and 190 conventional smears (58%), histologic follow-up was available. In 20 liquid-based preparations (71%) and 152 conventional smears (80.0%), cervical intraepithelial neoplasia (CIN) or higher was revealed on subsequent biopsy. Other results were as follows: liquid-based preparations, CIN1, 11 (55%); CIN2/3, 9 (45%); conventional smears, CIN1, 78 (51.3%); CIN2/3, 70 (46.1%); squamous cell carcinoma, 4 (2.6%). There was no statistically significant difference in the incidence of CIN or higher on subsequent biopsy after an interpretation of ASC-H based on preparation types. The incidences of CIN in patients 40 years old or older and patients younger than 40 years were 66% and 84%, respectively, a statistically significant difference. Because of the high incidence of clinically significant lesions noted on subsequent follow-up, patients with an interpretation of ASC-H should be observed closely and referred for colposcopic examination regardless of their age.