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 [controlled-trials.com].

Impact of the AutoPap (currently Focalpoint) primary screening system location guide use on interpretation time and diagnosis.

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.