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Summary: Background: The standard for reading cervical cytology is for a cytoscreener to manually search across an entire slide for abnormal cells using a conventional microscope. Automated technology can select fields of view to assess abnormal cells, which allows targeted reading by cytoscreeners. In the Manual Assessment Versus Automated Reading In Cytology (MAVARIC) trial, we compared the accuracy of these techniques for the detection of underlying disease. Methods: For this randomised controlled trial, women aged 25–64 years undergoing primary cervical screening in Manchester, UK, were randomly assigned (1:2) to receive either manual reading only or paired reading (automation-assisted reading and manual reading), between March 1, 2006, and Feb 28, 2009. In the paired arm, two automated systems were used—the ThinPrep Imaging System and the FocalPoint GS Imaging System. General practices and community clinics were randomised to either ThinPrep or to SurePath (for the FocalPoint system) liquid-based cytology with block randomisation stratified by deprivation index. Samples were then individually randomised to manual reading only or paired reading only. Laboratory staff were unaware of the allocation of each slide and concealment was maintained until the end of the reporting process. The primary outcome was sensitivity of automation-assisted reading relative to manual reading for the detection of underlying cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in the paired arm. This trial is registered, number ISRCTN66377374. Findings: 73 266 liquid-based cytology samples were obtained from women undergoing primary cervical screening; 24 688 allocated to the manual-only arm and 48 578 to the paired-reading arm. Automation-assisted reading was 8% less sensitive than manual reading (relative sensitivity 0·92, 95% CI 0·89–0·95), which was equivalent to an absolute reduction in sensitivity of 6·3%, assuming the sensitivity of manual reading to be 79%. Specificity of automation-assisted reading relative to manual reading increased by 0·6% (1·006, 95% CI 1·005–1·007). Interpretation: The inferior sensitivity of automation-assisted reading for the detection of CIN2+, combined with an inconsequential increase in specificity, suggests that automation-assisted reading cannot be recommended for primary cervical screening. Funding: National Institute for Health Research Health Technology Assessment programme. [Copyright &y& Elsevier]

Summary: Background: Testing for human papillomavirus (HPV) DNA is reportedly more sensitive than cytology for the detection of high-grade cervical intraepithelial neoplasia (CIN). The effectiveness of HPV testing in primary cervical screening was assessed in the ARTISTIC trial, which was done over two screening rounds approximately 3 years apart (2001–03 and 2004–07) by comparing liquid-based cytology (LBC) combined with HPV testing against LBC alone. Methods: Women aged 20–64 years who were undergoing routine screening as part of the English National Health Service Cervical Screening Programme in Greater Manchester were randomly assigned (between July, 2001, and September, 2003) in a ratio of 3:1 to either combined LBC and HPV testing in which the results were revealed and acted on, or to combined LBC and HPV testing where the HPV result was concealed from the patient and investigator. The primary outcome was the detection rate of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in the second screening round, analysed by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number ISRCTN25417821. Findings: There were 24 510 eligible women at entry (18 386 in the revealed group, 6124 in the concealed group). In the first round of screening 233 women (1·27%) in the revealed group had CIN3+, compared with 80 (1·31%) women in the concealed group (odds ratio [OR] 0·97, 95% CI 0·75–1·25; p>0·2). There was an unexpectedly large drop in the proportion of women with CIN3+ between the first and second rounds of screening in both groups, at 0·25% (29 of 11 676) in the revealed group and 0·47% (18 of 3866 women) in the concealed group (OR 0·53, 95% CI 0·30–0·96; p=0·042). For both rounds combined, the proportion of women with CIN3+ were 1·51% (revealed) and 1·77% (concealed) (OR 0·85, 95% CI 0·67–1·08; p>0·2). Interpretation: LBC combined with HPV testing resulted in a significantly lower detection rate of CIN3+ in the second round of screening compared with LBC screening alone, but the effect was small. Over the two screening rounds combined, co-testing did not detect a higher rate of CIN3+ or CIN2+ than LBC alone. Potential changes in screening methodology should be assessed over at least two screening rounds. Funding: National Institute of Health Research Health Technology Assessment Programme. [Copyright &y& Elsevier]

Abstract: This chapter reviews the contribution of cervical cytology, what makes it successful, the management of screen positives and how technological advances may affect its use in the future. Cervical screening has saved hundreds of thousands of lives but has not been available to women in the poorest countries. In countries where wide coverage has been achieved and quality assurance is in place, incidence and death rates have fallen by over 50% even though cervical cytology is logistically complex. The management of high-grade cervical intraepithelial neoplasia (CIN) is very effective, but low-grade cytological abnormalities require care to avoid over-treatment. The increasing rate of human papillomavirus (HPV) testing and the prospect of prophylactic vaccination will change the way cervical cytology is used, possibly giving way to HPV testing as the primary test in secondary prevention. [Copyright &y& Elsevier]