ThinPrep versus conventional Papanicolaou smear in the cytologic follow-up of women with equivocal cervical smears.

Department of Pathology, General Hospital of Bolzano, Bolzano, Italy. gneg@iol.it

BACKGROUND: The purpose of the current study was to compare the efficacy of liquid-based cytology and conventional smears in the cytologic follow-up of cases with "atypical squamous cells, cannot exclude a high-grade lesion" (ASC-H) or "atypical glandular cells" (AGC). METHODS: Cytologic follow-up was performed on 214 cases with ASC-H/AGC diagnosis an conventional smears using either ThinPrep (n = 100) or conventional Papanicoloau (Pap) tests (n = 114). Results were then compared with further histologic and/or cytologic follow-up. RESULTS: Repetition on conventional smears enabled a definite diagnosis (within normal limits [WNL], squamous intraepithelial lesion [SIL] or carcinoma) in 58 cases (50.9%). ASC/AGC was confirmed in 50 cases (43.9%), and 6 of the smears (5.3%) were inadequate. WNL, SIL, or carcinoma was diagnosed in 82 (82.0%) cases by following the patients with ThinPrep cytology, whereas ASC or AGC was confirmed in 18 cases (18.0%). No inadequate specimens were found. A diagnosis of SIL or greater (SIL +) was confirmed histologically in 11 of 11 (100.0%) conventional smears and in 31 of 34 (91.2%) ThinPrep specimens. Of the 87 WNL specimens, 9 (8 conventional smears and 1 ThinPrep specimen) developed a histologically confirmed SIL during further follow-up. Specimen adequacy was significantly better in the ThinPrep specimens compared with conventional smears. CONCLUSIONS: Because of better specimen adequacy, ThinPrep cervical cytology appears to significantly reduce the occurrence of ASC/AGC compared with conventional Pap smears.

结论：由于更多的标本量，ThinPrep宫颈细胞学同传统巴氏涂片比较似乎大大的降低了ASC/AGC（不确定）的诊断。

Comparison of performance of conventional and ThinPrep gynecologic preparations in the College of American Pathologists Gynecologic Cytology Program.

College of American Pathologists Gynecologic Cytology Program, Northfield, Ill., USA.

CONTEXT: Results of clinical trials suggest that interpretation of liquid-based cytology preparations is more accurate and is associated with less screening error than interpretation of conventional preparations. OBJECTIVE: In this study, the performance of participants in interpreting ThinPrep (TP) preparations was compared with participants' performance on conventional Papanicolaou tests in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP). DESIGN: The results of the PAP from the year 2002 were reviewed, and the discordancies to series and exact-match error rates for the 2 cytologic methods were compared. RESULTS: For this study, a total of 89 815 interpretations from conventional smears and 20 886 interpretations from TP samples were analyzed. Overall, interpretations of TP preparations had both significantly fewer false-positive (1.6%) and false-negative (1.3%) rates than those of conventional smears (P =.001 and P =.02, respectively) for validated or validated-equivalent slides, as assessed by concordance with the correct diagnostic series. In this assessment of concordance to series, interpretations of educational TP and conventional preparations were similar, except for high-grade squamous intraepithelial lesion, in which the performance was significantly worse for educational TP preparations (false-negative rate of 8.1% vs 4.1% for conventional smears, P <.001). When interpretations were matched to the exact diagnosis, validated-equivalent TP preparations were generally more accurate for diagnoses in the 100 series and 200 series than were conventional smears. Notably, for the reference diagnosis of squamous cell carcinoma, the exact-match error rate on validated equivalent TP slides was significantly greater than that of conventional slides (44.5% vs 23.1%, P <.001). Interpretations of educational TP preparations also had a significantly higher error rate in matching to the exact reference diagnosis for squamous cell carcinoma (33.7% vs 22.8%, P =.007). CONCLUSIONS: Overall, TP preparations in this program were associated with significantly lower error rates than conventional smears for both validated and educational cases. However, unlike the negative for intraepithelial lesion and malignancy, not otherwise specified, low-grade squamous intraepithelial lesion, and adenocarcinoma cytodiagnostic challenges, participants' responses indicated some difficulty in recognizing high-grade squamous intraepithelial lesion and squamous cell carcinoma.

结论：总之，液基细胞学在病例的验证和教育性（educational）两方面比传统涂片显著的降低了错误率。然而，和NILM、AGC-NOS(无具体指定）、LSIL和腺癌的细胞学诊断面临的挑战不同，与会者表达了在认识HSIL和鳞状细胞癌的一些困难。

Use of a liquid-based, thin-layer Pap test in a community hospital. Impact on cytology performance and productivity.

Department of Pathology, Decatur Memorial Hospital, 2300 North Edward Street, Decatur, Illinois 62526, USA.

OBJECTIVE: To evaluate the direct-to-vial efficacy of the SurePath Pap test (TriPath Imaging, Burlington, North Carolina, U.S.A.) in a community hospital laboratory and to assess its impact on productivity, as measured by Pap test turnaround times (TATs). STUDY DESIGN: A total of 8,771 SurePath Pap tests were compared to 5,055 conventional Pap smears collected and processed over the same 12-month period. SurePath histologic correlation rates were compared to historical correlation rates for conventional Pap smears. Pap test TATs for 3 months prior to implementing SurePath were compared to TATs for the last 3 months of the study, which included an approximate 70:30 ratio of SurePath to conventional Pap tests. Laboratory staffing was unchanged, and mean monthly accessions were relatively constant. RESULTS: SurePath showed statistically significant improvements in the detection of low grade (LSIL) (196%) and high grade (HSIL) (243%) squamous intraepithelial lesions (SILs) relative to conventional Pap smears. The atypical cells of undetermined significance (ASCUS) rate remained nearly constant with SurePath, while the ASCUS/SIL ratio decreased by 68%. Unsatisfactory rates declined 81%. Histologic correlation rates with SurePath increased over those of conventional Pap smears. Pap test mean TATs improved 73% with SurePath. CONCLUSION: Sure-Path detected significantly more cases of LSIL and HSIL than conventional smears without compromising specificity. The ASCUS/SIL ratio and unsatisfactory rate declined dramatically. Pap test TATs also improved markedly with SurePath.

结论：Sure-Path比传统涂片检测出了更多的LSIL和HSIL的病例而没有损害特性性。诊断ASCUS/SIL和不满意的病例的比率急剧减少。使用Sure-Path让筛查周期显著延长。

Cervical biopsy-based comparison of a new liquid-based thin-layer preparation with conventional Pap smears.

Department of Gynecology, Federal University of Sao Paulo, Escola Paulista de Medicina (UNIFESP-EPM), Sao Paulo, Brazil.

The objective of this study is to compare the diagnostic efficacy of universal collection medium (UCM) liquid-based cytology (LBC) (Digene Corp., MD) and the conventional Pap smear in a comparative study, using histologic results as the gold standard. This was a cross-sectional study. Conventional Pap smears and UCM LBC specimens, obtained from women in a low socioeconomic outpatient population referred to a tertiary center for gynecologic care, were compared. For the purpose of this study, when cervical specimens were collected for cytology, all women underwent colposcopy and biopsy was done if a cervical abnormality was observed. Cytologic evaluation of UCM LBC and conventional Pap smears were carried out separately, masked to the results of the other method. Agreement beyond chance between the two cytologic methods was ascertained by means of the unweighted kappa statistic. Sensitivity, specificity, and predictive values with 95% confidence intervals were calculated for both methods. McNemar's test was used to determine the level of association between the two cytology procedures. A total of 800 women were evaluated. Assessment of the overall agreement between the two cytologic methods yielded a kappa of 0.777 (P < 0.0001). After adjustment for histologic diagnosis, the computed kappa in each stratum was as follows: normal = 0.733; CIN 1 = 0.631; CIN 2/3 = 0.735; cancer = 0.652. The sensitivity and specificity of UCM LBC for detection of cervical intraepithelial lesions and cancer were 75.3% and 86.4%, respectively, not statistically different from the 81.8% and 85.2% seen with the conventional method. This study demonstrates that the UCM LBC method is as accurate as the conventional Pap smear cytology in detecting cervical intraepithelial lesions and cancer even so the UCM samples were systematically prepared from a second sampling of the cervix.

UCM(universal collection medium =普通集中收集)液基细胞学在CIN和癌的敏感性和特异性分别为75.3%和86.4%;同传统方法的81.8%和85.2%没有统计学的差异性。这个研究表明：即使UCM的样品是进行了系统地准备的第二次宫颈抽样，这种UCM液基细胞学方法同传统巴氏涂片在诊断CIN和癌上一样准确。

Liquid-based cytology in cervical screening: an updated rapid and systematic review and economic analysis.

The School of Health and Related Research The University of Sheffield, Sheffield, UK.

OBJECTIVES: To update an earlier published report reviewing the effectiveness and cost-effectiveness of liquid-based cytology (LBC). DATA SOURCES: Electronic bibliographic databases, relevant articles, sponsor submissions and various health services research-related resources. REVIEW METHODS: The selected data were reviewed and assessed with respect to the quality of the evidence. Pooled estimates of the parameters of interest were derived from the original and the updated studies. Meta-analyses were undertaken where appropriate. The mathematical model developed for the original rapid review of LBC was adapted to synthesise the updated data to estimate costs, survival and quality-adjusted survival of patients tested using LBC and using Papanicolaou (Pap) smear testing. Cost data from published sources were incorporated into the above model to allow economic, as well as clinical, implications of treatment to be assessed. The primary incremental cost-effectiveness ratio is the cost per life year gained (LYG), although estimates of the cost per quality-adjusted life-year (QALY) gained are also presented. A sensitivity analysis was undertaken to identify the key parameters that determine the cost-effectiveness of the treatments, with the objective of identifying how robust the results of the economic analysis are, given the current level of evidence. RESULTS: From the evidence available, it is likely that the LBC technique will reduce the number of false-negative test results. Modelling analyses undertaken as part of this study indicate that this would reduce the incidence of invasive cancer. There is now more evidence to support improvements emanating from the use of LBC screening in terms of a reduced number of unsatisfactory specimens and a decrease in the time needed to obtain the smear samples. The estimated annual gross cost of consumables and operating equipment, and other one-off conversion costs associated with introducing the new technique, will be between 17 British pounds and 38 British pounds million in England and Wales, depending on the LBC system and the configuration of the service. Analyses based on models of disease natural history, conducted in this study, showed that conventional Pap smear screening was extendedly dominated by LBC (LBC was always more cost-effective than conventional Pap smear testing over the same screening interval). Comparing LBC across alternative screening intervals gave a cost-effectiveness of under 10,000 British pounds per LYG when screening was undertaken every 3 years. The cost-effectiveness results were relatively stable under most conditions, although if screening outcomes such as borderline results and colposcopy are assumed to induce even small amounts of disutility then LBC screening at 5-yearly intervals may be the most cost-effective option. CONCLUSIONS: This updated analysis provides more certainty with regard to the potential cost-effectiveness of LBC compared with conventional Pap smear testing. However, there is uncertainty regarding the relative effectiveness (and cost-effectiveness) of the two main LBC techniques. Further research in the area of utility assessment may be worthwhile and possibly a full cost-effectiveness study of LBC based on a trial of its introduction in a low-prevalence population, although the results of the modelling analysis provide a robust argument that LBC is a cost-effective alternative to conventional cervical cancer screening. A randomised comparison of the two main techniques may also be useful.

结论：考虑到液基细胞学同传统巴氏涂片潜在的成本效益的比较，这种更新分析具有更大的确定性。但是，两种主要液基细胞学技术相对有效性（和成本效益）是存在不确定性的。基于液基细胞学在低使用人群的成本效益的充分研究，在这一领域的效用评估需近一步研究或许是值得和可能的。尽管这个模型分析结果为液基细胞学取代传统巴氏进行宫颈癌筛查提供了强有力的论据。但是两个主要技术的一项随机比较也可能是有用的。

Significance of atypia in conventional Papanicolaou smears and liquid-based cytology: a follow-up study.

Department of Pathology, Odense University Hospital, Odense, Denmark. doris.schledermann@ouh.fyns-amt.dk

The diagnosis of atypical squamous epithelial cells, borderline nuclear changes, is associated with some controversy, as it encompasses benign, reactive, as well as possible neoplastic conditions. The aim of this study was to evaluate the follow-up diagnoses of cytological atypia in conventional Papanicolaou smears (CP) and liquid-based samples by the ThinPrep Pap Test (TP). A total of 1607 CP smears from 1 January 2000 to 31 December 2000 and 798 TP samples from 1 January 2002 to 31 December 2002 diagnosed as atypia were included. The results show that the detection rate of atypia in cervical cytological samples was reduced by 41.3% (P < 0.001) in TP compared with CP. Cytological and histological follow-up data showed the presence of neoplastic lesions in 34.7% of patients screened by TP versus 22.3% of patients screened by CP, corresponding to a 55.6% increase in TP (P < 0.001). Follow-up diagnosis of mild dysplasia was seen more than twice as often in TP than in CP (12.8% versus 5.0%, P < 0.001). The prevalence of moderate and severe dysplasia was significantly increased with 26.7% in TP compared with CP (21.9% versus 17.2%, P < 0.01). In conclusion, the ThinPrep Pap Test yielded a significant decrease in atypia rates compared with the conventional Papanicolaou test. In subsequent follow-up the percentage of neoplastic lesions was significantly increased in the ThinPrep Pap Test samples.

结论，ThinPrep液基细胞实验比传统涂片实验在非典型细胞（ASC）诊断上明显的减少。随访中证实在肿瘤性病变的检出百分比有明显的增加。

Pap test in a high-risk population comparison of conventional and liquid-base cytology.

Division of Pathology of Adolfo Lutz Institute, 01246-902 São Paulo, Brazil.

Liquid-based cytology (LBC) is believed to have better sensitivity than conventional smears (CSs) and offers the possibility to perform molecular assay. The goal of this work was to study the performance of CS and LBC in a high-risk population and to compare the results with the hybrid capture (HC) II for high-risk human papillomavirus (HPV). Samples were collected from selected women with clinical suspicions of low genital tract lesion at Pérola Biygnton Hospital (São Paulo, Brazil). After CS preparation, the brush was introduced in the endocervix and a new sample was collected and rinsed in the preservative medium of the system. The residual material was used to HC2. From 925 cases, LBC was unsatisfactory in 4 (1.51%) cases and CS was unsatisfactory in 100 cases (10.81%); among theses cases HC2(+) reactions was observed in 54 (54%) CSs and 3 (21.4%) LBCs. Considering cases with atypia of undetermined significance (squamous and glandular), 85 (77.27%) cases from LBC and 44 (86.4%) from CS were positive for HC2 assay for high-risk DNA-HPV. The difference among the methods was not significant (P < 0.38). The diagnosis improvement of LBC in comparison with CS was 86% in satisfactory samples, 92.76% in undetermined atypical lesions (including glandular), 83% in positive low-grade squamous intraepithelial lesions (LSIL(+)), and 86.84% in high-grade SIL(+) (HSIL(+)). HC2(+) reactions were observed in 144 CS cases and 266 LBC cases with abnormalities. Our results have showed that LBC was superior to CS in a high-risk population to detect lesions with high concordance with HC2(+) reactions; CSs also exhibit a high concordance with HC2 assay but with inferior performance to detect lesions.

我们的研究结果表明液基细胞学大大优于传统涂片在高危人群病变的检出并与HC2阳性反应具有高的一致性。传统涂片也具有与HC2法高的一致性，但是病变检测方面较差。

Comparison of the SurePath liquid-based Papanicolaou smear with the conventional Papanicolaou smear in a multisite direct-to-vial study.

SeaCoast Pathology, 1 Hampton Road, Suite 108, Exeter, NH 03833, USA. mfremontsmith@yahoo.com

BACKGROUND: Split-sample clinical trials for liquid-based Papanicolaou (Pap) smears demonstrated that the liquid-based Pap smear was a safe and effective replacement for the conventional Pap smear. However, clinical intended use of liquid-based technology employs direct-to-vial collection methods. The current study compared the cytologic detection rates of the liquid-based Pap smear with conventional Pap smears in a direct-to-vial study performed at three clinical sites. METHODS: Data from 58,580 prospective SurePath slides and 58,988 historic conventional slides were collected. Results were statistically compared with regard to disease prevalence and adequacy to include biopsy follow-up data for conventional and SurePath tests. RESULTS: The SurePath method was found to provide a statistically significantly greater detection rate for clinically important categories of high-grade squamous intraepithelial lesion (HSIL+) and low-grade squamous intraepithelial lesion (LSIL+) (64% and 107%, respectively; P < 0.00001 for each lesion) compared with conventional slides. The clinical significance of increased cytologic detection using SurePath was supported by biopsy data that essentially demonstrated concordance with regard to biopsy interpretation for HSIL+ (P = 0.9105 at Site 1; P = 1.0000 at Site 2; and P = 1.0000 at Site 3) and LSIL+ (P = 0.6966 at Site 1; P = 0.8052 at Site 2; and P = 1.00 at Site 3). The detection rate of atypical squamous cells of undetermined significance (ASCUS+) was found to be significantly increased (75.12%; P < 0.00001). A statistically significantly lower proportion of unsatisfactory slides using the SurePath test compared with conventional slides was noted (-58%; P < 0.00001). The ASCUS/LSIL+ ratio was found to be reduced overall when using SurePath (-28.9%), regardless of whether the study sites were combined or considered individually. The rate of false-negative results noted with SurePath (10.43%) and conventional slides (12.97%) was essentially equivalent. CONCLUSIONS: The SurePath Pap smear was found to outperform conventional slides in the detection of HSIL+ and LSIL+ cytologic lesions of the cervix and reduced the number of unsatisfactory diagnoses. The HSIL+ advantage for SurePath is not limited to HSIL but appears to extend to carcinoma as well.

结论：SurePath 巴氏涂片超出传统巴氏涂片，在诊断HSIL以上及LSIL以上的病变和减少了不满意样本诊断的数量。SurePath对HSIL以上诊断的优势并不局限于HSIL，也表现在癌的诊断上。

Accuracy of liquid-based Pap tests: comparison of concurrent liquid-based tests and cervical biopsies on 782 women with previously abnormal Pap smears.

Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi, USA. mguo@mdanderson.org

OBJECTIVE: To evaluate the diagnostic performance of a liquid-based Pap test, the ThinPrep Pap test (TP) (Cytyc Corp., Boxborough, Massachusetts, U.S.A.), by comparing concurrent TP and cervical biopsy results on 782 patients who were referred for colposcopy because of previously abnormal conventional Pap smears (CPs). STUDY DESIGN: The ability of TP diagnoses of atypical cells of undetermined significance (ASC-US) and squamous intraepithelial lesions (SILs) to predict biopsy diagnoses of cervical intraepithelial neoplasia (CIN) was analyzed using chi2 and McNemar tests. RESULTS: The rate of agreement between diagnoses of SIL by TP and CIN by biopsy was 74.7%. ASC-US accounted for 16.0% of TP diagnoses. ASC-US had biopsy diagnoses of CIN 1 in 60% and CIN 2/3 in 12.8% of cases. For TP diagnosis of low grade SIL, biopsy diagnoses of CIN 2/3 were found in 13.5% of cases. For TP diagnoses of ASC-US and higher, the proportions of TP and cervical biopsies in comparable diagnostic categories were statistically significant (p < 0.001), with TP having sensitivity of 89.4% and positive predictive value of 89.7% for the detection of CIN. The false positive rate for TP was 8.1%, but rescreening confirmed the presence of abnormal cells in 51 of 63 (81.0%) cases of ASC-US or higher having negative biopsies. TP had a false negative rate of 8.3% and negative predictive value of 61.3%. Rescreening showed that most (77.6%) of the false negative TP specimens failed to have abnormal cells on the slides. CONCLUSION: For patients having previously detected cervical abnormalities by CP, concurrent TP demonstrated the following: (1) that it has high diagnostic accuracy for SIL, (2) that ASC-US was diagnostically equivalent to LSIL, and (3) that false negative TP for SIL can be attributed primarily to sampling rather than cytotechnologists' screening errors.

结论：患者通过传统巴氏涂片诊断宫颈异常，接着做液基细胞学会显示以下内容：1、对SIL有更高的诊断准确率，2、对ASCUS的诊断等同于LSIL，3、液基细胞学对SIL的诊断的假阴性主要是采样的原因，而不是细胞学技术员的筛查错误。

Correlation of conventional and liquid-based cytology and their meaning in management of precancerous cervical lesions.

Clinic for Gynecology and Obstetrics, Medical faculty, University "St Cyril and Methodi", Skopje, Macedonia.

AIM: Introduction of efficiency of liquid-based citoscreen cytology METHOD: Conventional cytology with Papanicolaou method and comparison with novel cytology liquid-based method in women with histological findings associated to Human Papilloma Virus praecancerous lesions for "gold standard" method. RESULTS: 100 women with praecancerous cervical lesions were included in the study. In all of the women, biopsy and endocervical curettage were made, and histological results were taken as a "gold standard". From the histology: LSIL was found in 64 women (64%) and HSIL in 36 women (36%). In LSIL, in 8 women the lesions are associated with existence of HPV or with coilocitic atipya and the other 56 women were with CIN 1. In group with HSIL, in 26 women was found CIN 2, 6 women were with CIN 3 and 4 women with CIS. In all women from both groups, conventional PAP and LBC cytoscreen were made. The results from conventional PAP were adequate in 42 women (42%), sub diagnosis in 34 (34%), over diagnosis in 10 (10%) and false-negative in 14 (14%). The results from LBC cytoscreen were adequate in 56 (56%), sub diagnosis in 22 (22%), over diagnosis in 16 (16%) and false-negative in 6 (6%). Sensitivity for PAP test is 84% and for LBC 94%. CONCLUSION: LBC cytoscreen method is better than the conventional PAP test in detection of the cervical epithlial abnormalities.

结论：液基细胞学细胞筛查方法在诊断宫颈上皮异常优于传统的巴氏实验。

DCS liquid-based system is more effective than conventional smears to diagnosis of cervical lesions: study in high-risk population with biopsy-based confirmation.

Division of Pathology, Adolfo Lutz Institute, Dr. Arnaldo Avenue, 355-Cerqueira Cezar, 01246-902 São Paulo, Brazil. longatto16@hotmail.com

OBJECTIVE: To compare the performances of Papanicolaou test (PapTest) and of a new liquid-based cytology method, DNA-Citoliq System (DCS), in a high-risk population, with histology confirmation. METHODS: Paired specimens of exfoliated cervical cells were collected under split-sample protocol. All patients were submitted to colposcopy and a biopsy taken when any atypical transformation zone was seen. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of both conventional and DCS methods were computed in relation to histology. RESULTS: A total of 1095 patients were analyzed by two cytology methods and, in 425 (38.8%), histologically. There were significantly more adequate samples with DCS (98.63%) than with conventional (89.6%) smears (P < 0.001). ASCUS was diagnosed significantly more with DCS than with conventional Pap (P < 0.001). Conventional Pap misclassified as normal 55.4% (158/285) of cases with either LSIL or HSIL or cancer at histology, whereas DCS misclassified 31.2% (89/285) of cases (P < 0.001). DCS had a significantly higher sensitivity (70% and 91.3%) than the conventional Pap (49.8% and 72.8%) to detect both LSIL+ and HSIL+ at histology, respectively. On the other hand, specificity of conventional smear (88.2% and 85.2%) was significantly higher than DCS (75.4% and 70.9%) considering both LSIL+ and HSIL+ at histology, respectively. CONCLUSIONS: This study confirms the superiority of the liquid-based cytology system DCS to detect cervical lesions. The rate of adequate DSC slides was significantly higher than with conventional cytology.

结论：这个研究表明液基细胞学系统（DCS=DNA-Citoliq系统）在检测宫颈病变的优越性。这种DCS涂片在满意度（The rate of adequate）方面大大优于传统涂片。

Erratum in:

Aust N Z J Obstet Gynaecol. 2005 Oct;45(5):352.

Comment in:

Aust N Z J Obstet Gynaecol. 2006 Feb;46(1):67.

Aust N Z J Obstet Gynaecol. 2006 Feb;46(1):70-1; author reply 71-2.

An alternative cost effectiveness analysis of ThinPrep in the Australian setting.

Pretium, Sydney, Australia. munro.neville@pretium.com.au

OBJECTIVE: To assess the clinical and economic impacts of the use of liquid based cytology (LBC) in the Australian average risk population from the perspective of the public health care budget. BACKGROUND: Concerns over the evaluation of medical technologies in Australia, which are assessed by the Medicare Services Advisory Committee (MSAC), have been raised recently. We report on the evaluation of LBC, which although being widely adopted in other parts of the world, has, despite substantial uptake in the private sector in Australia, been rejected for public funding by MSAC. METHODS: We used the health economic model developed by MSAC, but populated the model with the best available international data, sourced from a published review article. The economic model considered the clinical benefits and the costs arising from a biennial cervical screening programme. Net costs divided by life years saved is the cost per life year saved and this is reported as the incremental cost effectiveness. RESULTS: Populating the MSAC model with data on test performance showed that one type of LBC (ThinPrep) 'dominates' the conventional Pap smear in the screening of average risk women in the Australian setting. CONCLUSION: The health economic model created by MSAC predicts that ThinPrep dominates the conventional Pap as a screening test for cervical cancer. An additional 2240 high-grade lesions could be detected, resulting in 480 life years gained and delivering an expected saving to the health care system of $5,536,000 per annum if liquid based cytology replaced the conventional Pap.

 结论：通过医疗健康咨询委员会（MSAC）创建的健康经济模型预测ThinPrep占主导地位做为宫颈癌筛查的巴氏实验。如果用液基细胞学代替传统巴氏，每年会增加2240例HSIL的诊断，每年480个生命获得救治和每年卫生保健系统的费用会节省$5,536,000 。

The impact of converting to liquid-based cervical cytology in a military population.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Walter Reed Army Medical Center, 6900 Georgia Avenue NW, Washington, DC 20307, USA.

OBJECTIVE: The liquid-based cytology Pap test was adopted as the exclusive collection method for cervical cytology in military treatment facilities within the National Capital Area in 2001. We sought to determine the impact of converting from conventional to liquid-based cervical cytology. METHODS: A retrospective population-based study was performed to analyze the cervical cytology results from the National Capital Area for fiscal years 1999, 2000, 2002, and 2003. Using a computer database, the results of 78,738 conventional and 76,675 liquid-based cervico-vaginal cytology examinations were reviewed. All cytology samples during the study period were collected with the same collection device and were processed in a single laboratory. RESULTS: An increase of 116% (P < 0.005) in the mean rate of LSIL detection and a 38% (P < 0.005) increase in HSIL detection were noted with conversion to liquid-based cytology. A 65% (P < 0.005) decrease in the mean rate of atypical glandular cell detection was also observed. However, a mean increase of 46% (P < 0.005) per year was noted in the unsatisfactory rate with conversion to liquid-based cytology. The incidence of cervical carcinoma did not change during the study period. CONCLUSIONS: Consistent with previous reports, conversion from conventional to liquid-based Pap testing in this population resulted in a significant increase in the detection rates of both LSIL and HSIL. Contrary to earlier studies, we noted an almost 50% increase in the number of unsatisfactory samples after conversion. Further studies are warranted to determine the potential etiology of these findings to include the role of collection devices.

Conventional Pap smear and liquid-based cytology as screening tools in low-resource settings in Latin America: experience of the Latin American screening study.

Instituto Adolfo Lutz and Hospital Leonor M de Barros, São Paulo, Brazil. longatto16@hotmail.com

OBJECTIVE: To evaluate the performance of the conventional Pap test and liquid-based cytology (LBC) in an ongoing multicenter trial testing optional screening tools (cytology, screening colposcopy, visual inspection with acetic acid, visual inspection with Lugol's Iodine, cervicography and Hybrid Capture II [HCII] (Digene Brazil, São Paulo, Brazil) conventional and self-sampling), for cervical cancer in Brazil and Argentina. STUDY DESIGN: A cohort of 12,107 women attending four clinics (Campinas, São Paulo, Porto Alegre, Buenos Aires) were randomized into the 8 diagnostic arms. Women testing positive with any of the tests were referred for colposcopy, and cervical biopsies were used as the gold standard to assess performance characteristics of the diagnostic tests. Conventional Pap smears were sampled by all clinics (n = 10,240), and LBC (Autocyte PREP, [TriPath Imaging, Burlington, North Carolina, U.S.A.], n=320, and DNA-Citoliq [Digene Brazil], n =1,346) was performed by 1 of the clinics. RESULTS: Conventional Pap smears showed no squamous intraepithelial lesions (normal) in 8,946 (87.4%) and LBC in 1,373 (82.4%). Using high grade squamous intraepithelial lesions (HSIL) as the cutoff, Pap smears predicted high grade (cervical intraepithelial neoplasia [CIN] 3) with OR 63.0 (95% CI, 36.90-107.70), standard error (SE) 59%, SP 97.8%, positive predictive value (PPV) 68.1% and negative predictive value (NPV) 96.7%. The same figures for Autocyte PREP were: OR 9.0 (95% CI, 2.43-33.24), sensitivity (SE) 33.3%, specificity (SP) 100%, PPV 100% and negative PV (NPV) 88.8%. DNA-Citoliq detected CIN 3 as follows: OR 11.8 (95% CI 2.60-53.26), SE 40.0%, SP 94.6%, PPV 40.0% and NPV 94.6%. Lowering the cutoff to low grade squamous intraepithelial lesions increased SE and NPV but compromised SP and PPV. The detection rates for high grade lesions after an atypical squamous cells of undetermined significance diagnosis were similar with the 3 techniques. In our settings, the 3 methods of cervical cytology were slightly different in performance. The conventional Pap smear had the highest SE, while Autocyte PREP had 100% SP and PPV in detecting CIN3 with the HSIL cutoff. All 3 tests had lower SE but higher SP as compared to HCII.

在我们的实验设计中，宫颈细胞学三种方法的表现略有不同。传统巴氏涂片有最高的敏感性，但是Autocyte PREP 有100%的特异性和阳性预测值在检测HSIL中的CIN3。3种方法同HC2比较都有较低敏感性和更高的特异性。

Clinical results of a split sample liquid-based cytology (ThinPrep) study of 4,322 patients in a Turkish institution.

Department of Obstetrics and Gynecology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

PURPOSE: A prospective study was carried out to compare the efficacy of liquid-based cytology (ThinPrep) with the conventional Pap smear using a split-sample design in a Turkish university hospital outpatient gynecology clinic. METHODS: 4,322 consecutive patients were recruited for the study between 2002 and 2003. All the patients underwent conventional Pap tests followed by a ThinPrep test for screening of cervical cancer. The results were evaluated in terms of the Bethesda III classification. All the patients with abnormal tests underwent colposcopy and directed biopsy. RESULTS: While 2.3% of the specimens were unsatisfactory for evaluation in the conventional Pap test group, this rate was 1.7% for the ThinPrep group. Epithelial cell abnormalities were observed in 42 (1.0%) patients in the conventional Pap test group and in 36 (0.8%) patients in the ThinPrep group. ASCUS was observed in 26 patients in the conventional Pap test group whereas the ThinPrep group had 20 cases of ASCUS as the leading cause of abnormal cytology. Biopsy of these cases revealed CIN 1 in two CIN 2-3 in three and cervical/endometrial adenocarcinoma in three patients. The ThinPrep application led to diagnoses of one additional case of CIN 2-3 and one case of adenocarcinoma among the negative or unsatisfactory for evaluation categories of the conventional Pap test group. CONCLUSION: Despite an adverse bias introduced by the split-sample study design, application of ThinPrep showed an improved rate of specimen adequacy and increased sensitivity for more significant cervical precursor lesions over the conventional Pap test.

结论：尽管通过分组设计存在一些不利的偏差，但是应用ThinPrep表明在更为重要的宫颈癌前病变中提高了标本满意度和敏感性方面超过了常规巴氏试验。

Liquid-based cytology can improve efficiency of cervical smear readers: evidence from timing surveys in two NHS cytology laboratories.

Health Economics Research Group, Brunel University, Uxbridge, UK. robin.dowie@brunel.ac.uk

OBJECTIVE: Cervical screening programmes in England and Wales were advised by the National Institute for Clinical Excellence in 2003 to adopt liquid-based cytology (LBC) in place of conventional Papanicolaou (Pap) cytology to facilitate laboratory efficiency. Pilot evaluations in England and Scotland monitored daily or weekly workloads of smear readers and concluded that LBC could increase hourly throughput rates. This study, instead, used timing surveys to determine screening rates. METHODS: Two National Health Service cytology laboratories in Manchester and Stockport were partially converted to the LBC ThinPrep process for a cervical screening trial. Three 1-week timing surveys were conducted over 7 months. The surveys covered all LBC-trained staff. The first survey in Manchester also covered staff undertaking conventional Pap screening. The smear readers used timers to record time taken for examining and reporting each slide. RESULTS: In Manchester, in the first survey, nearly 1 minute per slide was saved by the LBC method during primary microscopy. In both laboratories, the mean microscopy time for primary screening of LBC slides was reduced by almost 1 minute between the first and second surveys. There was no difference between the second and third surveys. Microscopy by cytopathologists was also 1 minute per slide quicker with LBC than conventional Pap. The LBC inadequate rates for both laboratories were <2.0%. Organizational factors impacted on the hourly LBC primary screening rates in the laboratories, the rate for Stockport being higher than the rates in the pilot evaluations. CONCLUSIONS: The timing surveys confirm that the LBC ThinPrep technology can improve laboratory efficiency. However, decision-makers should also consider the overall costs and benefits of introducing the technology in screening programmes, including the capital investment and workforce implications.

Randomized Pilot Study Comparing Rates of Endocervical Cell Recovery between Conventional Pap Smears and Liquid-Based Cytology in a Pregnant Population.

Department of Obstetrics and Gynecology, Thomas Jefferson University Hospital, Philadelphia, PA.

OBJECTIVE.: To determine whether liquid-based cytology improves Pap smear adequacy, as defined by the presence of endocervical cells, compared with conventional cytology during pregnancy. MATERIALS AND METHODS.: A randomized pilot study was conducted between May 2001 and May 2002. Patients presenting for their first prenatal visit were randomized to receive either a conventional Pap smear or a liquid-based smear (ThinPrep). Rates of endocervical cell recovery and cytologic results were compared between the groups. RESULTS.: Eighty-one patients were enrolled in the study. There were no differences between the groups in age (p = .40), parity (p = .62), gestational age (p = .14), history of abnormal pap (p = .08), previous treatment of neoplasia (p = 1.00), and tobacco use (p = .67). Adequacy of the standard pap versus the liquid-based smear was not different between the two groups (90.5% vs 82.1%, respectively;p = .34). CONCLUSIONS.: The results of this pilot study show that rates of endocervical cell recovery in a pregnant population are not statistically different using conventional or liquid-based cytology. Further research is indicated to assess the utility of the more expensive ThinPrep technology in this population.

结论：这个研究的结果表明：在怀孕的人群中，用传统方法和液基细胞学宫颈细胞的获取率没有明显差异。评估在这一人群使用更加昂贵ThinPrep技术需进一步研究。

Evolution of Pap testing at a community hospital: a ten year experience.

Medical Director of Cytology, Rex Hospital, Raleigh, NC 27607-7505, USA. keith.nance@rexhealth.com

Over a 10-year period the Pap program at our community hospital laboratory progressed from the use of 100% conventional smears to predominantly ThinPrep (TP) and then to nearly 100% SurePath (SP). During this period the annual Pap volume grew from less than 20,000 to nearly 50,000. This retrospective review focuses on improvements in high-grade squamous intraepithelial lesion (HSIL) detection rates and specimen adequacy rates during the 10-year period.The laboratory database was used to identify 310,080 Pap test records between 1995 and 2004 inclusive. Pap type differences in HSIL detection rates and specimen adequacy rates were examined using the Cochran-Mantel-Haenszel test, with year as the stratification variable. The Breslow-Day test was used to evaluate the consistency of differences across the years. The overall results are summarized below in tabular format. Results of Combined 10-Year Data for Total Number of Cases, HSIL Rate, and Unsatisfactory Specimen Rate by Pap Method are given: [table: see text]. HSIL detection rates were significantly higher for liquid-based Pap tests compared with conventional smears (P < 0.0001). In addition, SP was associated with higher HSIL detection rates than TP with an estimated common odds ratio (OR) of 1.37 (95% confidence interval (CI), 1.10 - 1.71; P = 0.005), and higher specimen adequacy compared with TP or conventional Pap methods (P < 0.0001).

液基细胞学的HSIL病变检出率大大高于传统涂片（P<0.0001）。此外，SurePath在HSIL病变中比ThinPrep有更高的检出率和共同的比值比（OR）1.37（95%可信区间（CI），1.10-1.71；P=0.005）；并具有比ThinPrep和传统方法更多的样本量。

Comment in:

Am J Clin Pathol. 2007 Apr;127(4):489-91.

A follow-up study of atypical squamous cells in gynecologic cytology using conventional papanicolaou smears and liquid-based preparations: the impact of the Bethesda System 2001.

Department of Pathology, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

We evaluated the impact of the Bethesda System (TBS) 2001 in cytology reporting of atypical squamous cells (ASC) when using conventional Pap smears and liquid-based cytology preparations (LBC). Follow-up information for all ASC cases encountered in Queen Mary Hospital, Hong Kong, China, from July 2000 to June 2004 (using TBS 1991 in the first 2-year period and TBS 2001 in the second) was analyzed. Among 4, 089 ASC cases studied, more than 50% had negative follow-up; this percentage was lower with TBS 2001. The percentage of ASC cases with a low-grade cervical intraepithelial neoplasia (CIN) end point was higher with TBS 2001, especially after application of LBC. There was also a decreasing trend of having this low-grade CIN end point with advancing age. Most clinically significant outcomes occurred after 6 months and before 1 year post-ASC diagnosis. With TBS 2001, more than 50% of ASC, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) were associated with high-grade CIN on follow-up. TBS 2001 improves the positive predictive value of ASC for clinically significant lesions. Introduction of dichotomous subcategorization of ASC is relevant, with ASC-H associated with a much higher risk of subsequent high-grade squamous lesions.

低级别CIN的ASC病例百分比的终点高于使用2001年TBS系统；特别是在应用液基细胞学后。这种低级别CIN终点随着年龄也有下降的趋势在。最有临床意义的结果发生在前一次ASC诊断后6个月到1年之间。用2001年TBS系统，超过50％以上ASC-H的随访结果是高级别的CIN。2001年TBS系统提高了ASC阳性预测值为有临床意义的病变。与采用二分法ASC的次级分类有关，ASC-H具有比较高的高度鳞状病变的风险。

[Comparison of the ThinPrep monolayer technique and conventional cervical Pap smears in a high-risk population using the Munich II nomenclature]

Zytologisches Labor der Universitätsfrauenklinik Münster, Deutschland. info@lellenet.de

OBJECTIVE: In this prospective study using the Munich II nomenclature for cervical cytology. Pap smear results obtained by the ThinPrep monolayer technique and those obtained by the conventional method were compared. METHODS: Pap smears were obtained from 1,000 women using an Ayre spatula/endocervical brush combination. Following transfer of the cell sample onto a slide, the same collection devices were rinsed in a liquid medium and processed using ThinPrep-2000 processor (split-sample technique). RESULTS: Specimen inadequacies due to drying artefacts, cell overlap or low number of epithelial cells were rare with both methods without any significant differences. However, ThinPrep slides were significantly less often compromised by red or white blood cells or by cytolysis. In contrast, endocervical cells were missing in 11.6% of slides compared to only 2.3% in conventional Pap smears. ThinPrep yielded results of unknown significance (Pap III) significantly less often (4.2 vs 6.3%). CONCLUSIONS: ThinPrep slides are less frequently compromised by blood components or cytolysis. Inconclusive results of Pap III are slightly less frequent when using ThinPrep. However, there is a significant percentage of slides lacking the endocervical component. Using a combination of spatula and cytobrush, this may not necessarily be due to non-representative cell sampling. Copyright 2007 S. Karger AG, Basel.

结论：ThinPrep涂片较少被血液成份或细胞退变影响。没有结果Pap III（不能明确意义）的是略低于频繁使用ThinPrep。但是，有相当比例的液基片缺少宫颈成份。结合使用刮板和细胞刷取材，这是不必要由于非代表性的细胞样本。