Search

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., ((c) 2007 Wiley-Liss, Inc.)

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 [controlled-trials.com].

The study was aimed at assessing interlaboratory reproducibility in the reporting of cervical smears in the atypical squamous cells of undetermined significance (ASCUS) category. A set of 50 selected slides circulated among 89 laboratories, currently involved in population-based screening programmes for cervical cancer, which provided a diagnostic report according to four main reporting categories based on the 1991 Bethesda system. Interlaboratory agreement was determined according to kappa (K) statistics: overall and weighted K values were determined for each laboratory and for single reporting categories. The results showed a very low reproducibility for the ASCUS category. This finding supports the Bethesda system 1991 recommendation to limit the use of this reporting category and suggests that the clinical response to ASCUS reports should be decided locally, based on the observed positive predictive value for cervical intraepithelial neoplasia 2 or more severe lesions.

The study objective was assessing whether circulation of smears and discussion of those with differing interpretation can increase reproducibility between laboratories. The study included: the blind interpretation of a first set of 194 smears among seven laboratories, the discussion of smears with discrepant diagnoses during the previous phase and the blind interpretation of a second set of smears of same size and characteristics. After discussions, the overall weighted kappa increased in five laboratories (substantially in three : +50%, +27% and +20%). However, no change was observed in one laboratory and a slight decrease (-4%) in another. The latter interpreted the second set of smears at a longer time interval from discussions. Agreement improved for all diagnostic classes except low grade intraepithelial neoplasia (LSIL). Overall, the intervention increased diagnostic agreement, but its effect varied with laboratory and by diagnostic class and could be transient. Continued programmes of smear exchange and discussion appear to be advisable.

Background: AutoPap (currently Focalpoint) is a computerized scanning system for the primary screening of cervicovaginal smears. For smears indicated to require further review, the system provides maps (PapMaps) to identify the most abnormal areas of the smear., Methods: To study the effect of PapMaps on diagnosis, 481 smears (from 4656 successfully processed smears using AutoPap) were first classified by conventional manual interpretation and then reinterpreted blind by the same cytologist who limited his examination to only the fields of view marked by the PapMaps. The interpretation time with and without PapMaps was measured on another simple random sample of 188 smears., Results: The interpretation time was reduced significantly, by approximately 40% using PapMaps (average reduction, 136 seconds per smear, 95% confidence interval [CI], 123-150). No cases manually classified as low-grade squamous intraepithelial lesions (LSIL) or worse and 20% of those manually classified as atypical squamous cells of undertermined significance (ASCUS) were judged as completely normal on the basis of fields of visions marked by PapMaps. In none of the latter was a histologically confirmed intraepithelial lesion identified. In relation to detailed diagnosis, the weighted kappa between manual and PapMap-aided interpretation was 0.745 (95% CI 0.687-0.804). Systematic differences were found (symmetry chi-square(10d.f) =19.11, P = 0.039): 48% of smears classified as ASCUS and 23% classified as LSIL by conventional diagnosis were classified as less severe (including normal) on the basis of PapMaps., Conclusions: Use of PapMaps resulted in a substantial reduction in interpretation time. PapMaps showed good sensitivity (100% for squamous intraepithelial lesions and 80% for ACSUC) for selecting abnormal slides. The latter require full examination: detailed diagnosis based only on areas marked by PapMaps could lead to under-grading., (Copyright 2003 American Cancer Society.)

Introduction: Many studies have already shown the association of persistent infection of human high risk papillomavirus (HPV) with the development of pre-invasive and invasive cervical disease., Materials and Methods: We evaluated the use of high risk HPV testing in a study of about 1908 women, aged 29-78, who attending, from 1996 to 1998, the Sant'Anna Hospital in Turin for routine, second level smears and histopathological diagnosis. We considered all cervical lesions: ASCUS, LSIL, HSIL, squamous and adeno invasive cancers. HPV testing was performed by polymerase chain reaction (PCR) using L1 consensus primers which can detect almost all infections (high and low risk types). The most important high risk HPV types (16, 18, 31, 33 and 35) were tested using specific primers., Results: The prevalence of high risk HPV was: ASCUS 42.2%, LSIL 39%, HSIL 73.5%, squamous invasive cancers 98.3% and adeno 100%. In addition HPV 16 is the most represented type in all lesions: ASCUS 40%, LSIL 62%, HSIL 71.2% squamous invasive cancers 73.3% and adeno 50.6%. In addition we study the mean age of cervical cancer onset compared with the different high risk HPV types. We found that HPV 18 related cancer occurs in younger women (mean age 41 years; range 39-42)., Conclusions: The addition of high risk HPV testing to cytology may improve early identification of women at risk for cervical cancer.