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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]

The article presents arguments in favor of human papillomavirus (HPV) primary cervical screening. Topics discussed include some large randomised trials which showed that HPV testing is more sensitive than cytology for detecting underlying high-grade cervical intraepithelial neoplasia (CIN), and the fact that some cases of CIN stage 3 are caused by non-vaccine types.

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]

Potential roles for HPV testing in cervical screening.The most important clinical value of HPV testing in thelower genital tract is to distinguish women at very low riskof malignancy from those at some risk.In cervical screening, the principal roles that HPV testingmay play are(i) in primary screening,(ii) in following up the treatment of cervical abnormalities,(iii) triage of mild abnormalities.Study findingsThe ASCUC-LSIL triage study (ALTS) investigated the sensitivityof HPV testing using HC II combined with repeat cytologyin detecting CIN3+ lesions (Table 1) [11].Further results from the ALTS study, in which 897 cases oflow-grade squamous intraepithelial lesion (LSIL) and 1193cases of HPV DNA-positive ASCUS were followed for 2 years,suggested that LSIL lesions and HPV-positive ASCUS areclinically equivalent [12]. Initial colposcopic detection of obviouslyprevalent CIN2+ reduces risk. However, for the remainingwomen who have CIN ≤ 1 on colposcopy and directedbiopsy, the risk for subsequent CIN grade 2 or 3 isapproximately 12% over 2 years.The HPV in addition to routine testing (HART) studylooked at the management of women who tested positivefor high-risk types of HPV, but had negative or borderlinescreening abnormalities [13]. HPV testing was more sensitivethan borderline-or-worse cytology (97.1% versus 76.6%,P = .002), but less specific (93.3% versus 95.8%, P < .0001)for detecting CIN2+. Surveillance at 12 months was as effectivefor monitoring progression as immediate colposcopy.From study results to clinical practiceA meta-analysis to assess the accuracy of HPV DNA testingas an alternative to repeat cytology in women who had equivocalresults on a previous Pap smear suggests thatHC II assayhas higher sensitivity and similar specificity than the repeatPap smear (ASCUS as threshold) for CIN2+ among womenin this patient group [14].HPV testing has a high negative predictive value and althoughthe positive predictive value is lower, it offers considerablebenefits in triaging patients. It can also assist decisionmaking on behalf of women with mild cytological abnormalities. [ABSTRACT FROM AUTHOR]

Cervical cancer is caused by human papillomavirus infection. Most human papillomavirus infection is harmless and dears spontaneously but persistent infection with high-risk human papillomavirus (especially type 16) can cause cancer of the cervix, vulva, vagina, anus, penis, and oropharynx. The virus exclusively infects epithelium and produces new viral particles only in fully mature epithelial cells. Human papillomavirus disrupts normal cell-cycle control, promoting uncontrolled cell division and the accumulation of genetic damage. Two effective prophylactic vaccines composed of human papillomavirus type 16 and 18, and human papillomavirus type 16,18, 6, and 11 virus-like particles have been introduced in many developed countries as a primary prevention strategy. Human papillomavirus testing is clinically valuable for secondary prevention in triaging low-grade cytology and as a test of cure after treatment. More sensitive than cytology, primary screening by human papillomavirus testing could enable screening intervals to be extended. If these prevention strategies can be implemented in developing countries, many thousands of lives could be saved. [ABSTRACT FROM AUTHOR]