Maria Paola Cariaggi

Accuracy of liquid based versus conventional cytology: overall results of new technologies for cervical cancer screening randomised controlled trial

Objective To compare the accuracy of conventional cytology with liquid based cytology for primary screening of cervical cancer. Design Randomised controlled trial. Setting Nine screening programmes in Italy. Participants Women aged 25-60 attending for a new screening round: 22 466 were assigned to the conventional arm and 22 708 were assigned to the experimental arm. Interventions Conventional cytology compared with liquid based cytology and testing for human papillomavirus. Main outcome measure Relative sensitivity for cervical intraepithelial neoplasia of grade 2 or more at blindly reviewed histology, with atypical cells of undetermined significance or more severe cytology considered a positive result. Results In an intention to screen analysis liquid based cytology showed no significant increase in sensitivity for cervical intraepithelial neoplasia of grade 2 or more (relative sensitivity 1.17, 95% confidence interval 0.87 to 1.56) whereas the positive predictive value was reduced (relative positive predictive value v conventional cytology 0.58, 0.44 to 0.77). Liquid based cytology detected more lesions of grade 1 or more (relative sensitivity 1.68, 1.40 to 2.02), with a larger increase among women aged 25-34 (P for heterogeneity 0.0006), but did not detect more lesions of grade 3 or more (relative sensitivity 0.84, 0.56 to 1.25). Results were similar when only low grade intraepithelial lesions or more severe cytology were considered a positive result. No evidence was found of heterogeneity between centres or of improvement with increasing time from start of the study. The relative frequency of women with at least one unsatisfactory result was lower with liquid based cytology (0.62, 0.56 to 0.69). Conclusion Liquid based cytology showed no statistically significant difference in sensitivity to conventional cytology for detection of cervical intraepithelial neoplasia of grade 2 or more. More positive results were found, however, leading to a lower positive predictive value. A large reduction in unsatisfactory smears was evident. Trial registration Current Controlled Trials ISRCTN81678807.

Solid nonpalpable breast lesions Success and failure of guided fine-needle aspiration cytology in a consecutive series of 2444 cases

Purpose: To evaluate the contribution of guided fine-needle aspiration cytology in reducing unnecessary biopsies of benign solid nonpalpable breast lesions with low suspicion of malignancy at mammography. Material and Methods: An evaluation was made of a consecutive series of 2444 solid nonpalpable breast lesions detected by mammography and undergoing guided (sonography or stereotaxy) fine-needle aspiration cytology. Surgical biopsy was made in the presence of strong suspicion of malignancy at mammography and/or of abnormal cytology. Results: The sensitivity was 96.7% and the specificity 77.7% (average follow-up 2.77 years). False-negative/inadequate cytology associated with low suspicion of malignancy at mammography resulted in a diagnostic delay in 27 cancer cases (invasive 20, intraductal 7). On the other hand, cytology led to surgical biopsy in 53 cancer cases which might not otherwise have been biopsied because of low radiological suspicion of cancer. Surgical biopsy of all cases, to avoid diagnostic delays, would have increased the benign biopsy rate by a factor of 4.5, with a rise in the benign: malignant biopsy ratio from 0.44:1 to 1.93:1. Conclusion: Stereotaxy- or ultrasound-guided fine-needle aspiration cytology of nonpalpable mammographic abnormalities can achieve a sharp reduction in unnecessary benign biopsies in cases of low suspicion of malignancy at mammography.

Triage with human papillomavirus testing of women with cytologic abnormalities prompting referral for colposcopy assessment

The current study was conducted to evaluate the cost‐effectiveness of triaging for colposcopy using human papillomavirus (HPV) testing.

A Feasibility Study of the Use of the AutoPap Screening System as a Primary Screening and Location-Guided Rescreening Device

The AutoPap 300 QC system (Tripath Imaging, Inc., Burlington, NC) is an automated device that was designed to screen conventionally prepared cervical smears and, more recently, thin‐layer slide preparations. The system has been tested in large clinical trials.

Is Conventional Urinary Cytology Still Reliable for Diagnosis of Primary Bladder Carcinoma? Accuracy Based on Data Linkage of a Consecutive Clinical Series and Cancer Registry

Objective: Reported urine cytology accuracy, particular sensitivity, is highly variable. We evaluated the accuracy of urinary cytology for primary bladder cancer using population data linkage to provide valid estimates. Study Design: Consecutive cytology tests processed through a major service between January 2000 and December 2004 were linked to a regional population cancer registry (allowing outcome ascertainment). Sensitivity and specificity were calculated using different thresholds, based on standardized reporting categories (C1 = negative, C2 = reactive, C3 = atypical, C4 = suspicious, C5 = malignant, Cx = inadequate). Results: Cancer registry matching of 2,594 tests revealed 130 incident bladder cancers, of which 97 occurred within 12 months of cytology and were included in calculating accuracy. Sensitivity (C3–C5 considered positive) ranged between 40.2 and 42.3%, and specificity was 93.7–94.1%. If C3 results are counted as negative, sensitivity estimates reduced to 24.7–26.0%. The positive predictive value of a C3, C4 or C5 report was 11.7, 39.2, and 66.6%, respectively. High tumor grade was associated with significantly higher sensitivity compared to low and intermediate grades combined (p = 0.02). Conclusion: Urine cytology is highly specific but has intermediate sensitivity, indicating that it has a role in adjunct diagnosis, but not in screening for primary bladder cancer. C3 results should be considered ‘positive’ and further investigated, and all positive results should prompt further intervention.

Analysis of morphologic patterns of fine-needle aspiration of the breast to reduce false-negative results in breast cytology.

The identification of specific morphologic diagnostic criteria is of paramount importance to optimize the accuracy of fine‐needle aspiration cytology (FNAC) and to reduce the rate of false‐negative results. In the current study, the authors reviewed a consecutive series of false‐negative findings observed in the study center to define the presence and degree of cytologic abnormalities. False‐negative cases were randomly mixed with true‐negative cases and were reviewed by a panel of expert readers in a blinded fashion. The main objective of the current study was to identify a morphologic pattern that may permit the reduction of false‐negative findings while maintaining the specificity of FNAC.

PERFORMANCE OF FINE-NEEDLE ASPIRATION CYTOLOGY OF THE BREAST-MULTICENTER STUDY OF 23,063 ASPIRATES IN TEN ITALIAN LABORATORIES

Aims and background The aim of this study was to assess the performance of routine breast cytology in a group of Italian laboratories, as a basis for interlaboratory quality control. Methods A multicenter retrospective consecutive series of 23,063 aspirates from breast lesions (5,130 invasive carcinoma, 247 intraductal carcinoma, 2,386 benign lesions [histological], 13,144 benign lesions [follow-up], 2,156 other [no follow–up]) was reviewed. Standard accuracy measurements (inadequacy rate, sensitivity, specificity, predictive value) were determined, as well as the contribution of diagnostic tests such as physical examination and instrumental diagnostic procedures (mammography, sonography). Results Overall, inadequacy rate was 6.5% for malignant and 23.2% for benign lesions. Sensitivity was 92.2%, specificity was 95.3%, and the positive predictive value of an equivocal or malignant report was 53.4% or 96.9%, respectively. Sensitivity was associated with histological type (intraductal vs invasive: 77.0% vs 92.9%, p < 0.000001; lobular vs other invasive: 85.5% vs 94%, p = 0.0025) as well as with tumor size (pT1 = 91.6%, pT2 = 94.3%, pT3–4 = 96.0%, p < 0.000001). Observed differences in performance indicators between centers may be explained by variability in sampling or reading accuracy, and warrant the need for some adjustment in single centers, especially, as far as the criteria to report an equivocal smear are concerned. Cytology contributed to detect otherwise unsuspected carcinomas, although in some centers this benefit was poor and not cost-effective because a large number of unnecessary biopsies were caused by false equivocal/positive reports. Conclusions Although centers scored, on average, well within standards recommended by national authorities, this study suggests the opportunity of interlaboratory quality control to achieve more homogeneous criteria.

Reliability of sparing Papanicolaou test conventional reading in cases reported as No Further Review at AutoPap-assisted cytological screening: survey of 30,658 cases with follow-up cytological screening.

AutoPap‐assisted smear reading has been proposed prior to conventional manual reading; the latter may be unnecessary for cases reported as No Further Review (NFR) and would be required for cases reported as Review (REV).

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

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 κ 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.

Detection of false-negative Pap smears using the PAPNET system.

Aims and background False-negative cytological diagnoses represent the critical point of a screening program for early detection of cervical cancer. Computer-assisted reading using neural network technology has been suggested as a possible approach to manage the problem. The study assessed the performance and the cost-outcome ratio of computer-assisted versus conventional manual Pap smear reading. Methods One thousand routine smears, seeded with 81 false-negative smears, were independently interpreted by two readers by conventional and PAPNET-assisted reading. Results of both readings were compared in terms of: a)sensitivity for false-negative smears, b)specificity, and c) cost-outcome (cost per CIN2+ lesion detected). Results PAPNET-assisted reading showed a small increase in sensitivity only for one reader. Including the cost of PAPNET, the cost per detected lesion would be