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。

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.

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 。

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。

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。

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。

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。

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。

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。

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。

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。

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。

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。

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。

Comment in:

Cancer. 2004 Jun 25;102(3):200; author reply 200-1.

Liquid-based cytology and conventional cervical smears: a comparison study in an Asian screening population.

Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong, China. anycheun@hkucc.hku.hk

BACKGROUND: This study compared the findings of cervical cytology screening by ThinPrep Papanicolaou (Pap) tests (TP) with the findings of screening by conventional cervical smears (CS) in a screening population involving what to the authors' knowledge is the largest sample of ThinPrep Pap tests published to date. METHOD: Data from 191,581 CS that were screened in the period from March 1, 1998 to February 28, 2000 were compared with data from 190,667 TP performed from March 1, 2000 to February 28, 2002 and that were obtained from the same sources. RESULTS: With TP, the unsatisfactory rate was reduced from 0.48% to 0.32%. Fewer cases were considered to be suboptimal (19.12% vs. 12.97%). The detection rates of squamous cell carcinomas, adenocarcinomas, and high-grade squamous intraepithelial lesions (HSIL) were essentially unchanged in the TP group (0.005%, 0.003%, and 0.25%, respectively) compared with the rates for the CS group (0.01%, 0.006%, and 0.25%, respectively). There was an increase in the detection of atypical squamous cells of undetermined significance (ASCUS; 3.74% vs. 3.19%) and low-grade SIL (LSIL; 1.67% vs. 1.01%) with a decrease in the ASCUS-to-LSIL ratio from 3.15 for CS to 2.33 for TP. The detection of atypical glandular cells of undetermined significance (AGUS) increased slightly from 0.07% to 0.09%. The proportion of cells reported to have reactive atypia dropped from 2.71% to 1.48%. Limited biopsy correlation (range, 73.2-76.2%) confirmed the increased sensitivity of TP. More actinomyces (1.07% vs. 0.52%) were detected in TP samples despite of a similar portion of intrauterine-device users. The average primary screening and rapid rescreening time of each slide were reduced from 8 minutes to 4 minutes and from 2 minutes to less than 1 minute, respectively. CONCLUSIONS: The preliminary experience of the authors of the current study appears to support the use of the ThinPrep Pap test to enhance the efficiency of cervical cytology screening.

结论：以作者目前研究的初步经验表明支持用ThinPrep巴氏实验做宫颈细胞学筛查以提高效率。

Cytohistologic correlation rates between conventional Papanicolaou smears and ThinPrep cervical cytology: a comparison.

Cytopathology Division of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. mary.chacho@yale.edu

BACKGROUND: The ThinPrep Papanicolaou (Pap) test, a liquid-based alternative to the long-used conventional Pap smear, received Food and Drug Administration approval in 1996. The current study is a comparison of the accuracy, as assessed by cytohistologic correlation, of conventional versus ThinPrep Pap smears in a hospital setting. METHODS: A retrospective analysis of all patients who underwent Pap smears (conventional and ThinPrep) and pertinent surgical pathology tissue processed in our department over a 1-year period was undertaken. Tissue diagnoses were grouped into broad general categories to correlate with the Bethesda system. The statistical significance of differences between the two types of Pap test results compared with tissue diagnoses was assessed using a chi-square test with 1 degree of freedom and an alpha value of 0.05. RESULTS: Of the 65,421 Pap smears interpreted during the study period, histologic correlation was possible in 1544 patients. Of those diagnosed as negative (644 conventional and 245 ThinPrep Smears), low-grade squamous intraepithelial lesion (LGSIL) (116 conventional and 114 ThinPrep smears), and high-grade squamous intraepithelial lesions (HGSIL) (142 conventional and 131 ThinPrep smears), there was no statistically significant difference found between the correlation rates of conventional and ThinPrep Pap smear results. However, review of all cases of invasive cervical carcinoma identified during this time period showed the ThinPrep to be less consistent in predicting the presence of invasive carcinoma compared with the conventional Pap smear. CONCLUSIONS: Based on cytohistologic correlation evidence, the ThinPrep Pap test may not be more effective in detecting cervical disease, particularly invasive carcinoma, when compared with the conventional Pap smear.

结论：基于细胞组织学相关证据，ThinPrep巴氏实验同传统巴氏涂片比较没有更有效的检测出宫颈病变、特别是浸润癌。

Positive predictive value of liquid-based and conventional cervical Papanicolaou smears reported as malignant.

Department of Obstetrics and Gynecology, University of Vermont College of Medicine, Burlington, USA.

OBJECTIVES: The predictive value of cervical Papanicolaou (Pap) smears reported as "positive for malignancy," especially those obtained by the liquid-based method, has not been adequately assessed. The objectives of this study are to determine the positive predictive value of Papanicolaou smears with features of malignancy, to compare the accuracy of Papanicolaou smears obtained by the liquid-based method to those obtained by the conventional technique in this setting, and to study the factors influencing a false-positive cytologic diagnosis of malignancy. MATERIALS AND METHODS: Pap smears significant for malignant cytology were identified at Fletcher Allen Health Care Hospital in Burlington, VT, from May 1, 1995, to April 30, 2001. A retrospective review of the hospital records and pathology reports was performed documenting patient characteristics, the collection technique, and the final histology. An independent review of the cytology and histology was performed. The positive predictive value and false-positive rate of malignant cytology were calculated for the liquid-based and conventional Pap smear techniques. RESULTS: A total of 472,743 Pap smears were performed during the period specified. One hundred four Pap smears were reported as positive for malignancy, yielding a prevalence rate of 0.02%. A total of 68 patients had paired cytology and histology specimens. Malignant cytology was identified in 36 smears obtained by the liquid-based technique and 32 smears obtained by the conventional technique. A true-positive result, meaning malignant cytology confirmed by the presence of invasive carcinoma on histology, was obtained in 61 of 68 (89.7%) patients. A false-positive result, meaning malignant cytology not confirmed by histology, was obtained in 7 of the 68 (10.3%) patients. The false-positive rate of malignant cytology was 8.4% for the liquid-based technique and 12.5% for the conventional technique. All 7 false-positive smears were diagnosed with high-grade dysplasia by histology. Three of the 7 patients with high-grade dysplasia had previous treatment for dysplasia, one of whom was also pregnant at the time of the smear. CONCLUSIONS: Malignant cervical Papanicolaou smear cytology has a high positive predictive value in the setting of gynecologic and nongynecologic malignancies. Previous treatment for cervical dysplasia or pregnancy may influence the false-positive rate of malignant cytology.

Conventional pap smear and liquid-based cervical cytology smear: comparison from the same patient.

Cytopathology Unit, Borgo San Lorenzo Hospital, Florence, Italy. conforti@plugit.net

BACKGROUND: The results of blind reading of smears obtained with liquid-based cytology in patients previously screened by conventional cytology were compared. MATERIAL AND METHODS: Cases selected for the study were a consecutive series of 99 subjects undergoing colposcopy within the screening program of the Florence District. The Pap test samples were processed utilizing the Thin Prep 2000 (Cytyc Corporation, Boxborough, MA). The liquid-base cytology smears were randomly admixed and read by seven expert cytologists with more than 15 years of experience in Pap smear reading. For each case, a consensus diagnosis was created and considered as the definitive diagnosis. Cytologic reports in conventional and liquid-based cytology smears were compared by the kappa statistic to evaluate diagnostic agreement. RESULTS: The study showed that the conventional and liquid-based cytology provide comparable cytologic reports and that the latter is not less sensitive than the former in detecting CIN2+ lesions of the cervix. DISCUSSION: Such evidence suggests the feasibility of randomized studies comparing the two methods, which are needed before adopting liquid-based cytology as the current method when screening for cervical cancer.

讨论：这种证据表明了随机研究比较这两种方法的可行性，采用液基细胞学做为宫颈癌筛查的方法之前的研究是必须的。

Conventional and liquid-based cervicovaginal cytology: a comparison study with clinical and histologic follow-up.

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68498-7549, USA. jbaker@unmc.edu

Increased rates of squamous intraepithelial lesion (SIL) diagnosis with liquid-based cervicovaginal cytology (CVC) methods are well documented. This retrospective study compares the ability of the ThinPrep Pap Test (TP) and the conventional Pap smear (CP) to detect biopsy-proven SIL and to exclude nonneoplastic disease. All CVC reports from January 1999 through December 2000 from seven community Family Medicine clinics affiliated with the University of Nebraska were reviewed. For women with at least one CVC diagnosis of epithelial cell abnormality (ECA), follow-up histology, cytology, and clinical data were obtained. Statistical analysis was performed using the chi-square method. SIL was diagnosed in 166 of 3,286 patients by TP (5.1%) and in 169 of 4,872 patients by CP (3.5%) (P < 0.001); 32 of the TP diagnoses (1.0%) and 34 of the CP diagnoses (0.7%) were high-grade SIL (HSIL). Atypical squamous or glandular cells of undetermined significance (ASCUS/AGUS) was the most severe abnormality diagnosed by TP in 218 patients (6.6%) and by CP in 279 patients (5.7%). Follow-up histology data on CVC SIL diagnoses showed evidence of cervical intraepithelial neoplasia in 94 patients screened by TP (2.9%) and in 79 patients screened by CP (1.6%) (P < 0.001); the biopsy diagnoses were CIN 2 or CIN 3 in 34 patients in the TP group (1.0%) and in 28 patients in the CP group (0.6%) (P < 0.025). Follow-up of patients in whom the first ECA CVC diagnosis was ASCUS or AGUS disclosed a positive predictive value for CIN of 22.8% for TP ASCUS/AGUS diagnoses and 11.9% for CP ASCUS/AGUS diagnoses (P < 0.005). In this population, TP was significantly better than CP in detecting biopsy- proven disease and in screening out benign abnormalities.

在这群人中的活检证实病变和良性异常改变检测中，液基细胞学实验大大优于传统涂片。

Histologic follow-up of atypical endocervical cells. Liquid-based, thin-layer preparation vs. conventional Pap smear.

Department of Pathology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio, USA.

OBJECTIVE: To review the histologic findings in patients diagnosed with "atypical glandular cells of uncertain significance, endocervical cell type" (AGUS-EC) by ThinPrep Pap Test (TPPT) or conventional Pap smear (CPS) and to evaluate the clinical value of subclassifying AGUS-EC as "favor reactive" or "favor neoplastic." STUDY DESIGN: All TPPT and CPS diagnosed as AGUS-EC (favor reactive, unspecified and favor neoplastic) from January 1998 through December 1999 and all available histologic follow-up (defined as endocervical curettage, cervical biopsy, cervical conization or hysterectomy obtained within six months of the time of an AGUS-EC diagnosis) were obtained from a computerized database. RESULTS: AGUS-EC was diagnosed in 0.77% of CPS (683 of 88,825) and 0.59% of TPPT (183 of 30,968) (P = NS). There was no statistically significant difference in any of the follow-up histologic diagnoses between the CPS and TPPT groups. The majority of the follow-up biopsies demonstrated benign processes in both groups. Patients with a diagnosis of AGUS-EC "favor neoplastic" had a greater proportion of true glandular pathology as compared with AGUS-EC "unspecified" or "favor reactive" (P < .001). None of the patients with a diagnosis of AGUS-EC "favor reactive" were found to have true glandular pathology; however, a minority of them proved to have squamous pathology. CONCLUSION: In this study there was no difference in CPS and TPPT in regard to the specificity of a diagnosis of AGUS-EC for true glandular pathology. Subclassifying AGUS-EC as "favor reactive" or "favor neoplastic" may provide valuable information for directing patient follow-up.

结论：在这个研究中，通过确诊的腺体病理证实ThinPrep实验同传统巴氏涂片在诊断AGC（颈管来源）的特异性没有差异。AGC（颈管来源）的次分类“AGC倾向反应性”或“倾向肿瘤”为指导病人的后续追踪提供了宝贵的信息。（注：2001版之前的TBS语言都改为2001版的语言）