Does liquid-based technology really improve detection of cervical neoplasia? A prospective, randomized trial comparing the ThinPrep Pap Test with the conventional Pap Test, including follow-up of HSIL cases.

Cytology Laboratory of Jörg H. Obwegeser, Zurich, Switzerland. zylabob@swissonline.ch

OBJECTIVE: To compare the sensitivity, specificity and specimen adequacy of the ThinPrep Pap Test (TP) with the conventional Pap Test (CV) in a low-risk population with subsequent follow-up of HSIL cases. STUDY DESIGN: A prospective, randomized, controlled design was chosen to compare the TP with CV. Cytologic diagnosis and specimen adequacy were evaluated and compared with histology data in high grade squamous intraepithelial lesion (HSIL) cases. Fifteen gynecologists in private practice, all trained in colposcopy, participated in the trial. Cytologic diagnosis, specimen adequacy and follow-up of the cytologic HSIL cases were compared in the two groups. In total, 1,999 patients were included, 997 in the TP group and 1,002 in the CV group. Randomization assignments were designated on cytology case report forms, which were placed in sealed envelopes. Each envelope had a sequential randomization number on the outside to allow tracking and authentication of randomization assignments. RESULTS: Comparison of results between CVs and TPs revealed no statistically significant differences in all diagnostic categories, ranging from "within normal limits" to HSIL. Specimen adequacy, however, was superior with CVs (P < .001). The cytologic diagnosis of HSIL correlated with the histologic diagnosis in 91% of the TP group and 100% of the CV group. CONCLUSION: Because there was no statistically significant difference in sensitivity and specificity of the two techniques, improved detection of cervical abnormalities and better specimen adequacy might not be a consequence of utilizing liquid-based preparations but of a better sampling technique. Removing mucus and cellular debris from the cervical surface with a cellulose swab before sampling cells with a proper sampling device results in the same sensitivity and specimen adequacy and is much less expensive than the liquid-based technique.

结论：因为两种技术在敏感性和特异性上没有显著性的统计学差异。提高了检测宫颈的异常情况和更多样本量可能不是使用液基的结果，而是用了更好的采样技术。在用适当采样工具之前，用纤维素拭子从宫颈表面去除黏液和细胞碎片，得到的结果是同液基技术相同的敏感性和充足的标本量并便宜得多的花费。

Liquid-based cytology for primary cervical cancer screening: a multi-centre study.

Institut Alfred Fournier, 25 boulevard Saint Jacques, Paris, 75014, France.

The aim of this six-centre, split-sample study was to compare ThinPrep fluid-based cytology to the conventional Papanicolaou smear. Six cytopathology laboratories and 35 gynaecologists participated. 5428 patients met the inclusion criteria (age > 18 years old, intact cervix, informed consent). Each cervical sample was used first to prepare a conventional Pap smear, then the sampling device was rinsed into a PreservCyt vial, and a ThinPrep slide was made. Screening of slide pairs was blinded (n = 5428). All non-negative concordant cases (n = 101), all non-concordant cases (n = 206), and a 5% random sample of concordant negative cases (n = 272) underwent review by one independent pathologist then by the panel of 6 investigators. Initial (blinded) screening results for ThinPrep and conventional smears were correlated. Initial diagnoses were correlated with consensus cytological diagnoses. Differences in disease detection were evaluated using McNemar's test. On initial screening, 29% more ASCUS cases and 39% more low-grade squamous intraepithelial lesions (LSIL) and more severe lesions (LSIL+) were detected on the ThinPrep slides than on the conventional smears (P = 0.001), including 50% more LSIL and 18% more high-grade SIL (HSIL). The ASCUS:SIL ratio was lower for the ThinPrep method (115:132 = 0.87:1) than for the conventional smear method (89:94 = 0.95:1). The same trend was observed for the ASCUS/AGUS:LSIL ratio. Independent and consensus review confirmed 145 LSIL+ diagnoses; of these, 18% more had been detected initially on the ThinPrep slides than on the conventional smears (P = 0.041). The ThinPrep Pap Test is more accurate than the conventional Pap test and has the potential to optimize the effectiveness of primary cervical cancer screening.

ThinPrep实验是比传统巴氏实验更准确和具有做为初次宫颈癌筛查的潜在的高效率。

Comment in:

Cancer. 2000 Feb 25;90(1):67-9.

Utility of liquid-based cytology for cervical carcinoma screening: results of a population-based study conducted in a region of Costa Rica with a high incidence of cervical carcinoma.

Women & Infants Hospital, Brown University, Providence, Rhode Island 02905-2401, USA.

BACKGROUND: In a study using a split-sample design, liquid-based cytology (ThinPrep Processor, Cytyc Corporation, Boxborough, MA) was compared with the conventional Papanicolaou (Pap) smear in Guanacaste, Costa Rica. The study provides the first population-based comparison of the ThinPrep screening technology and includes "gold standard" measures of diagnostic accuracy. METHODS: The population-based study was performed among over 8000 women residing in a Costa Rican province with a high incidence of cervical carcinoma. Conventional smears were prepared and diagnosed in Costa Rica, while the residual material on the sampling device was collected into a liquid preservative and shipped to the U.S., where ThinPrep cytologic slides were prepared and diagnosed. Cytologic diagnoses based on the two techniques, categorized according to the Bethesda System, were compared with a "gold standard" final case diagnosis for each patient, also based on Bethesda terminology, that reflected an integrated interpretation of all available data, including cytology, histology, and cervicography. Results were also compared with the results of HPV DNA detection (Hybrid Capture, Digene Corporation, Silver Spring, MD). RESULTS: ASCUS was the threshold for colposcopy referral. There were significantly more women referred according to this threshold with the ThinPrep slide (12.7%) than with the conventional smear (6.7%, P<0.001). Compared with the final case diagnosis, referral by ThinPrep slides detected 92.9% of cases with high grade squamous intraepithelial lesions (HSIL) and 100% of carcinoma cases. Smears detected 77.8% of HSIL and 90.9% of carcinomas. Thus, ThinPrep cytology was significantly more sensitive in the detection of HSIL and cancer (McNemar test, P<0.001). Adjudication of cases in which the ThinPrep and smear diagnoses disagreed, using the final case diagnoses and the HPV DNA test results as reference standards, suggested that the ThinPrep method was detecting additional true SIL as opposed to false-positives. CONCLUSIONS: In a population-based study of high risk women, ThinPrep cytology demonstrated significantly increased sensitivity for detecting HSIL and carcinoma, with a concurrent significant increase in colposcopy referrals.

结论：在一个人口为基础的高风险妇女的研究中表明ThinPrep细胞学显著提高检测HSIL和癌的敏感性，同时大大增加了阴道镜的推广。

[Comparison of conventional PAP smears with thin layer specimen (liquid-based PAP test) and correlation with cytopathological findings with HPV status using the hybrid capture system]

Spital Pflegi-Neumünster, Zürich.

Cervical smears of 554 outpatients of a hospital were examined using a blinded, split sample match pair protocol for which a conventional PAP-smear (CS) was first prepared with Cervex brush and the reminder of the sample was used for the thin-layer-preparation (TLP) according to the manual CytoRich System. The preparations of the two methods were compared with respect to quality and to sensitivity for atypias. In addition the HPV status was determined on the same cell suspension in cases with borderline changes (BLC) and dysplasias including carcinoma using the Hybrid Capture System. The use of TLP reduced the proportion of suboptimal preparations by more than 50% (14.6% vs. 35%) and eliminated the only inadequate preparation registered in CS. The DSP detected more than twice as many dysplasias of all degrees as CS (3.4% vs. 1.4%) and reduced the proportion of BLC to one third (3.2% vs. 9.6%). The percentages of cases positive for high- and intermediate-risk HPV in preparations with BLC, LSIL and HSIL were 17, 62.5% and 100% respectively. The TL-method improves significantly the efficiency of PAP-smears and allows the typing of HPV which is of clinical importance for the management of low grade squamous intraepitelial lesions and borderline changes. The findings speak against the further use of CS for cervical screening.

这种薄层方法比传统巴氏涂片大大提高了效率和通过HPV的分型对LSIL和交界性改变进行重要的临床管理。这个结果表明反对进一步的用传统巴氏涂片进行宫颈癌筛查。