A comparison of liquid-based cytology and Pap smear as a screening method for cervical cancer.

Department for Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska University Hospital at Huddinge, Karolinska Institute, S-141 86 Stockholm, Sweden.

The implementation of population-based screening for cervical cancer with Pap smear in the early sixties was set to detect and treat precancerous lesions, hopefully preventing a subsequent invasive cervical cancer. Epidemiological data indicate that organized screening has a major impact on morbidity and mortality from cervical cancer. The limited sensitivity of a single smear necessitates repeated smears in organized program. It is suggested that liquid-based cytology improves the sensitivity. The aim of this split-sample study was to compare ThinPrep liquid-based cytology with conventional Pap smear, relying on a laboratory with long-term experience of the latter. In total, 137 women with atypical Pap smear in population-based cervical screening were enrolled for the split-sample study. The performance of both techniques (ThinPrep liquid-based cytology and conventional Pap smear) were compared and validated by a histological follow-up. Women without representative histological biopsy were excluded from the study. Pap smear had sensitivity for detection of CIN2-3 of 47% compared to 66% for liquid-based material. The concordance of the two sampling techniques with the histological diagnosis was 37% and 53%, respectively, this difference being statistically significant. The proportion of reports on atypical squamous cells of undetermined significance (ASCUS) was significantly less in the liquid-based material, 4.3% compared to 8% of the conventional smears. This improved sensitivity in combination with the possibility to perform reflex testing such as HPV DNA or p16 immunocytochemistry without renewed sampling gives ThinPrep a substantial advantage and makes the liquid-based technique interesting.

Direct-to-vial comparison of a new liquid-based cytology system, liqui-PREP versus the conventional pap smear.

Department of Clinical Pathology, EONE Reference Laboratory, Seoul, Korea. lovefate@hanafos.com

The objective of the study was to assess the clinical utility of a liquid-based cytology system on cervicovaginal screening in a clinical commercial laboratory. Twenty-six thousand, one hundred and seventy eight cervicovaginal specimens were prepared by the Liqui-PREP (LGM International Inc., Ft. Lauderdale, FL) with a direct-to-vial comparison to 218,548 cases of the conventional direct smear from August 2005 through December 2005. Biopsy data was obtained to confirm the sensitivity for each method. Liqui-PREP showed a marked increase in HSIL+ detection compared to the conventional smear ( P = 0.001). The rate of LSIL and AGC detection was higher with Liqui-PREP ( P equals; 0.001 for both). The percentage of ASCUS specimens was higher than with conventional smear due to cleaner slides and easier detection of suspicious cells. The WNL rate was lower for Liqui- PREP ( P = 0.001) consistent with increased HSIL+ and ASCUS. The unsatisfactory rate was lower for Liqui-PREP ( P = 0.017). The histological predictive value of Liqui-PREP was slightly higher than the conventional smear (94.1% versus 89.9%). The Liqui-PREP system similar to other reported LBC technologies shows an increased detection of squamous intraepithelial lesions, and gives higher-quality slides for interpretation than the conventional smear. Histological results confirm that this increase in cytological findings are clinically significant. LGM's new LBC technology is a more sensitive screening tool when compared with the conventional smear. Copyright 2007 Wiley-Liss, Inc.

黑体字：Liqui-PREP（液基）的预测值略高于常规涂片（ 94.1 ％比89.9 ％ ）。该Liqui-PREP（液基）系统类似于其他已报道的液基技术，增加鳞状上皮内病变的检出，同传统的涂片比较并制出了更高质量的涂片。组织学结果证实：这增加细胞学结果的临床意义。相比较传统涂片，LGM新的液基细胞学技术是一种更加敏感的筛查工具。

Liquid-based cytology versus conventional Papanicolaou smear in an organized screening program : a prospective randomized study.

Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Goteborg and Sahlgrenska University Hospital, Goteborg, Sweden.

BACKGROUND: The objective of this study was to evaluate whether liquid-based cytology (LBC) can improve high-standard cervical cancer screening cytology further. The primary endpoint was histopathologic high-grade lesions in current and subsequent screening rounds. The secondary endpoints were cytologic diagnosis and inadequate samples. METHODS: Women were randomized to smear taking by conventional Papanicolaou (Pap) smear or LBC according to the time of appointment. Eight thousand eight hundred ten conventional Pap smears and 4674 LBC samples were included. Evaluations of atypical cytology and referral to colposcopy and treatment were performed as routine procedures. Histopathologic diagnoses were retrieved from a regional database 8 months after the study was closed. The mean follow-up was 2 years and 9 months. RESULTS: Inadequate samples were observed in 0.3% of LBC samples versus 0.7% of Pap smears (P = .002). The total fraction of nonbenign diagnoses in cytology was 4.5% versus 3.5%, respectively (P < .001). Histopathologic evaluation was made on 570 patients constituting 4.6% of the LBC samples and 4% of the Pap smears. Forty percent more high-grade lesions were identified as a result of LBC sampling (1.20% vs 0.85%; P = .05). The influence of the sampling method was significant for all variables (odds ratio [OR], 1.60; 95% confidence interval [95% CI], 1.12-2.28) for high-grade lesions that were identified by histology when adjusting for age and screening unit in a logistic regression model. At the second follow-up 2 years and 1 month later, the OR was decreased only slightly (1.51; 95% CI, 1.13-2.01). CONCLUSIONS: In the ongoing cervical screening program of western Sweden, liquid cytology produced a significantly higher yield of histologic high-grade lesions compared with conventional Pap smears.

结论：正在瑞典西部进行的宫颈筛查项目。同传统涂片相比较，液基细胞学大大提高了组织学高级别病变的检出率。

Comparison of two preparation methods for endocervical evaluation.

Department of Pathology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Republic of Korea.

OBJECTIVE: To assess the validity of SurePath liquid-based preparation method for examination of endocervical brush specimens as a substitute for conventionally prepared cytology methods for evaluating the endocervical canal during colposcopic examination and biopsy. STUDY DESIGN: Paired SurePath liquid-based test slides and conventional smears were obtained using an endocervical brush in a split sample protocol before biopsy at the time of colposcopy. The level of agreement between cytologic results obtained was assessed. Accuracy and operating characteristics were evaluated compared to histologic follow-up. RESULTS: Agreement between cytology results for the methods was excellent. The overall kappa was 0.924 (p = 0.0000). There was exact agreement on interpretation between the methods in 283 of 299 cases (94.6%). Cytohistologic follow-up results correlation were: SurePath liquid-based Pap test results and conventional smear results agreed with histology results in 47.8% and 49.2% of cases, respectively. Allowing for a discrepancy within 1 level of severity of cytologic grade, agreements were 76.6% and 77.2%, respectively. CONCLUSION: This study demonstrates that the SurePath method is equivalent to conventional endocervical brush cytology preparation and performs well for detection of cervical intraepithelial lesions and cancer. SurePath is acceptable for endocervical evaluation as a substitute for endocervical curettage at colposcopic biopsy.

结论：这个研究表明这种SurePath方法相当于传统的刷取细胞学和对检测CIN和癌效果良好。在阴道镜活检前，SurePath在子宫颈评估中取代子宫颈刮板是可以接受的。

Scientific Institute of Public Health, Brussels, Belgium. marc.arbyn@iph.fgov.be

OBJECTIVE: To compare test performance characteristics of conventional Pap tests and liquid-based cervical cytology samples. DATA SOURCES: Eligible studies, published between 1991 and 2007, were retrieved through PubMed/EmBase searching and completed by consultation of other sources. METHODS OF STUDY SELECTION: Studies were selected if a conventional and a liquid-based sample were prepared from the same woman or when one or the other type of sample was taken from a separate but similar cohort. The current systematic review and meta-analysis is restricted to studies where all subjects were submitted to gold standard verification, based on colposcopy and histology of colposcopy-targeted biopsies, allowing computation of absolute and relative test validity for cervical intraepithelial neoplasia grade 2 or worse. Randomized trials were selected as well if all test-positive cases were verified with the same gold standard, allowing computation of the relative sensitivity. Impact of study characteristics on accuracy was assessed by subgroup meta-analyses, meta-regression, and summary receiver operating characteristic curve regression. TABULATION, INTEGRATION, AND RESULTS: The relative sensitivity, pooled from eight studies, with complete gold standard verification and from one randomized clinical trial, did not differ significantly from unity. Also, the specificity, considering high-grade and low-grade squamous intraepithelial lesions as cutoff, was similar in conventional and liquid cytology. However, a lower pooled specificity was found for liquid-based cytology when presence of atypical squamous cells of undetermined significance was the cutoff (ratio 0.91, 95% confidence interval 0.84-0.98). Differences in study characteristics did not explain interstudy heterogeneity. CONCLUSION: Liquid-based cervical cytology is neither more sensitive nor more specific for detection of high-grade cervical intraepithelial neoplasia compared with the conventional Pap test.

结论：液基宫颈细胞学同传统巴氏实验比较：对高级别CIN而言，既没有更高的敏感性也没有更高的特异性。

Interobserver reproducibility with LiquiPrep liquid-based cervical cytology screening in a developing country.

Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

OBJECTIVE: A modified liquid-based techniques known as the "LiquiPrep (LP) system" requires neither expensive equipment nor complicated specimen preparation. The aim of this study was to assess the applicability of the LP for use in a developing country. METHODS: Cervical cytology specimens were collected from 777 women, using the Cervex-Brush. The brush was first smeared on a glass side for conventional Papanicolaou (CP) stain, and then immersed in preservation fluid for LP preparation. Cytologic interpretations were classified into four categories: 1) no atypical cells, 2) atypical squamous epithelial cells (ASC), 3) definite epithelial cell abnormality, and 4) unsatisfactory specimen. Interobserver variability was tested using weighted kappa statistics. RESULTS: An LP specimen cost $9 per case compared to $3 per case for a conventional Pap smear. The time to learn the technique was only a few days. Forty six (5.92%) specimens by LP were unsatisfactory. The overall agreement between cytopathologists was 96.7% (weight kappa=0.62), with 95.6% (weight kappa=0.44) for the cases enrolled earlier, increasing to 97.9% (weight kappa=0.78) for the cases enrolled later. CONCLUSIONS: In summary, after a short learning curve, interobserver reproducibility of LP smear was near perfect. This feature of the LP, together with the relatively low cost and simple protocol, makes it quite suitable for cervical cytology screening in developing countries. Moreover, with this technique, some of each sample can be reserved for additional studies such as HPV detection and subtyping.

Follow-up study of atypical glandular cells in gynecologic cytology using conventional Pap smears and liquid-based preparations: impact of the Bethesda System 2001.

Department of Pathology, The University of Hong Kong and Hong Kong Sanatorium and Hospital, Hong Kong Special Administrative Region, China.

OBJECTIVE: This study evaluated the impact of the Bethesda System (TBS) 2001 in reporting of atypical glandular cells (AGC) when using conventional Pap smears (CS) and liquid-based cytology preparations (LBC). STUDY DESIGN: Follow-up information for all atypical glandular cells of undetermined significance (AGUS)/ AGC cases encountered in Queen Mary Hospital from July 2000 to June 2004 was analyzed. The difference in percentages associated with certain end points when using different reporting systems and preparation methods were compared. The age trends and time interval between cytologic diagnosis and detection of positive end points were studied. RESULTS: More than half of these cases turned out to be "negative." The majority with "negative" end points belonged to the "not otherwise specified" (NOS) groups (including atypical endometrial cells) in TBS 2001. The connotation of "favor neoplastic" carried a high positive predictive value for significant lesions. Most of the significant outcomes were discovered within the subsequent 6 months. A decreased reporting of "AGC, NOS" and an increased reporting of "atypical endocervical cells, NOS" were noted when using LBC. CONCLUSION: Subcategorization of AGC in TBS 2001 according to cellular origin and risk of malignancy, which is further enhanced by application of LBC, is useful.

结论：在2001年TBS系统中AGC这个次级分类中，根据细胞来源和恶性肿瘤的风险；是进一步加强了液基细胞应用价值和意义。

Performance of 3 methods for quality control for gynecologic cytology diagnoses.

Pathology Division, Adolfo Lutz Institute, Department of Pathology, Federal University of São Paulo, Sã Paulo, Brazil.

OBJECTIVE: To evaluate performance and viability of internal quality control (QC) strategies in a public health laboratory of the state of São Paulo. STUDY DESIGN: A retrospective study was performed with 3 QC strategies to improve internal cytologic diagnoses: morphologic guided-list criteria (MGLC), 100% rapid-rescreening (100% RR) of negative slides ("turret" method) and 10% rescreening (10% R) of negative slides. Cases were examined at Adolfo Lutz Institute, São Paulo, Brazil, from 2002 to 2004. Histopathologic results, when available, were considered gold standard; cytologic consensus diagnosis was by 2 pathologists when histologic results were unavailable. RESULTS: MGLC selected 20.7% samples with cytologic atypias, 10% R selected 0.6% and RR selected 2.5%. Cytologic/histologic initial concordance was 57.4%, low-grade squamous intra-epithelial lesion false negative rate was 34.9% and high-grade squamous intraepithelial lesion false negative rate was 12.2%. After diagnosis, consensus concordance was 97.2%. CONCLUSION: The 100% RR and 10% R QC strategies detected more false negative cases in liquid-based cytology than in conventional Pap smears. The 100% RR strategy reduced the false negative results and allowed evaluation of individual staff performance. The 10% R strategy did not offer significant results. We concluded that association of MGLC and 100% RR strategies might improve cytologic diagnostic quality.

结论：液基细胞学同传统涂片比，（阴性涂片）100%快速复阅和10%复阅的质控策略检测出更高的假阴性病例。100%快速复阅策略降低了假阴性结果和评估个别工作人员的业绩。10%复阅（阴性涂片）策略没有提供有意义的结果。我们可以得出结合大纲性（导向性）的形态学标准（morphologic guided-list criteria）和100%快速复阅（阴性涂片）的策略会提高细胞学诊断的质量。

Endometrial carcinoma detected with SurePath liquid-based cervical cytology: comparison with conventional cytology.

Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.

C. Patel, A. Ullal, M. Roberts, J. Brady, P. Birch, J. N. Bulmer and V. Wadehra Endometrial carcinoma detected with SurePath liquid-based cervical cytology: comparison with conventional cytologyIntroduction: Conventional Pap smears (CPS) have little impact on the detection of endometrial carcinoma. Although liquid-based cytology (LBC) is replacing CPS in the UK, experience with identification of endometrial cancers with this technique is limited. Aim: To compare the accuracy of the SurePath LBC with that of CPS for detection of endometrial cancers. Methods: Our study group comprised SurePath LBC samples reported as atypical endometrial cells and endometrial adenocarcinoma (classified respectively as borderline, code 8 and ?glandular neoplasia, code 6 for the NHS Cervical Screening Programme statistics) in 2004-2005. CPS reported as atypical endometrial cells or adenocarcinoma in 1993-1998 comprised the control group. Histological follow-up was obtained. Results: Endometrial abnormalities were reported in 95 (0.073%) of 130 352 LBC samples, comprising 75 (0.058%) atypical endometrial cells and 20 (0.015%) endometrial adenocarcinoma reports. Of 409 495 CPS, 117 (0.029%) were diagnosed as endometrial abnormalities, comprising 59 (0.014%) atypical endometrial cells and 58 (0.014%) endometrial adenocarcinoma reports. Thus, the endometrial adenocarcinoma reporting rate was similar in both groups, but that for atypical endometrial cells was higher with LBC (P < 0.001). The positive predictive value for endometrial cancer of endometrial adenocarcinoma and atypical endometrial cell reports in the LBC group was 73.3 and 18.8%, respectively, compared with 42.3 and 6.7% in the CPS group. The endometrial adenocarcinoma patients in CPS group were older (mean age 62.5 years versus 56.5 years) and most (22/25) were symptomatic, whereas most (13/17) patients in the LBC group were asymptomatic at the time of sampling (P < 0.001). Conclusion: SurePath LBC is at least as accurate a method for detecting endometrial cancer as CPS. SurePath LBC demonstrates enhanced identification of endometrial pathology in asymptomatic women in the cervical screening programme.

只翻译结论部分：

SurePath 液基制片至少是一种同传统涂片一样准确的检测子宫内膜癌的方法。SurePath 液基制片表明在宫颈筛查项目中，加强无症状妇女的子宫内膜病理的鉴定诊断。