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. INTRODUCTIONLiquid based cytology is used widely for primary screening of cervical cancer but high quality studies on its accuracy are limited. Indeed almost all published studies are based either on the comparison of non-randomly assigned populations or on double testing the same women. With the double testing design, cells used for diagnosis could be removed with the conventional sample, which is taken first, leading to an underestimation of the accuracy of liquid based cytology. In addition only some of the published studies, in a primary screening setting, considered histologically confirmed cervical intraepithelial neoplasia as the end point and only a few verified the diagnosis by colpohistology in the large majority of women with abnormal cytology results. A recent review identified one small randomised trial only and concluded that large randomised trials were needed.

Spoiled gradient echo sequences can only reach a homogeneous steady state if sufficiently strong crusher gradients are used in combination with RF phase cycling (RF spoiling). However, the signal depends quite sensitively on the chosen phase increment ϕ and—lacking analytical solutions—numerical simulations must be used to study the transient and steady‐state magnetization. For the steady state an exact analytical solution is derived, which holds for arbitrary sequence and tissue parameters. Besides a considerably improved computation performance, the analytical approach enables a better understanding of the complicated dependence on ϕ. For short repetition times (TR) the regime of small ϕ turns out to be particularly interesting: It is shown that the typical ϕc, where RF spoiling starts to become effective, is essentially inversely proportional to T2. This tissue dependence implies that contrasts can be considerably larger with partial spoiling (ϕ ≈ ϕc) than with conventional RF spoiling (ϕ ≫ ϕc). As an example, the uptake of contrast agents in tissues is investigated. For typical parameters a considerably improved contrast enhancement can be obtained, both theoretically and experimentally. Magn Reson Med, 2006. © 2005 Wiley‐Liss, Inc.

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.

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A set of 300 vaginal smears was interpreted by 13 cytologists from six European laboratories, who were requested to report inadequate and suboptimal smears. The set had been appropriately seeded to reach approximately 10% inadequate and 20% suboptimal smear frequency. According to the majority report, 230 smears were classified as adequate (76.7%), 43 as inadequate (14.3%), and 27 as suboptimal (9.0%). Agreement with the majority report ranged from 52% to 91% (average 78%). Kappa statistics for reporting inadequate smears showed a high level of agreement for five cytologists, and fair to good agreement for eight. In contrast, kappa statistics for reporting suboptimal smears showed fair to good agreement with the majority report only in five instances, whereas agreement was poor for eight cytologists. 'Inadequate smear' rates may be used to compare the quality of smears received in different laboratories, as there is a high level of agreement among cytologists as to what constitutes an inadequate smear. However, this is not true for "suboptimal smear" rates, and more precise reporting criteria must be defined and tested if an intermediate category is to be retained to report poor quality smears: more precise reporting criteria must be defined and tested if an intermediate category is to be retained to report poor quality smears.

Within a multicentre controlled trial framework, an external quality control (EQC) was scheduled to evaluate the interlaboratory reproducibility of liquid-based cytology. In particular, this EQC intended to evaluate the reproducibility of the ASCUS diagnosis.A selected set of 30 slides (4 within normal limit cases, 16 atypical squamous cells of undetermined significance; 4 low-grade squamous intraepithelial lesions and 6 high-grade squamous intraepithelial lesions) circulated among the 13 laboratories involved in the trial.Kappa values were obtained from the comparison between individual laboratory diagnoses and majority diagnoses with target diagnoses. Specific kappa values resulted moderate to high for HSIL and low to moderate for LSIL and WNL. Meanwhile, the specific kappa for ASCUS was below 0.4 in 12 of 13 participating laboratories. The lack of reproducibility for ASCUS was not a result of the introduction of this new technology but rather to the low reproducibility of the ASCUS category itself stemming from intrinsic uncertainties in the reporting criteria.

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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.