Randomised Evaluation of New Technologies within the Population‐Based Cervical Cancer Screening Programme in Finland: Cross‐Sectional Performance and Validity

A randomised and population-based screening design with new technologies has been applied to the organised cervical cancer screening programme in Finland. In this experiment the women invited to routine five-yearly screening are individually randomised to be screened with automation-assisted cytology, human papillomavirus (HPV) test or conventional cytology. By using the randomised design, the ultimate aim is to assess and compare the long-term outcomes of the different screening regimens. The primary aim of the current study was to evaluate, based on the material collected during the implementation phase of the Finnish randomised screening experiment, the cross-sectional performance and validity of automation-assisted cytology (Papnet system) and primary HPV DNA testing (Hybrid Capture II assay for 13 oncogenic HPV types) within service screening, in comparison to conventional cytology. The parameters of interest were test positivity rate, histological detection rate, relative sensitivity, relative specificity and positive predictive value. Also, the effect of variation in performance by screening laboratory on age-adjusted cervical cancer incidence was assessed. Based on the cross-sectional results, almost no differences were observed in the performance of conventional and automation-assisted screening. Instead, primary HPV screening found 58% (95% confidence interval 19-109%) more cervical lesions than conventional screening. However, this was mainly due to overrepresentation of mild- and moderate-grade lesions and, thus, is likely to result in overtreatment since a great deal of these lesions would never progress to invasive cancer. Primary screening with an HPV DNA test alone caused substantial loss in specificity in comparison to cytological screening. With the use of cytology triage test, the specificity of HPV screening improved close to the level of conventional cytology. The specificity of primary HPV screening was also increased by increasing the test positivity cutoff from the level recommended for clinical use, but the increase was more modest than the one gained with the use of cytology triage. The performance of the cervical cancer screening programme varied widely between the screening laboratories, but the variation in overall programme effectiveness between respective populations was more marginal from the very beginning of the organised screening activity. Thus, conclusive interpretations on the quality or success of screening should not be based on performance parameters only. In the evaluation of cervical cancer screening the outcome should be selected as closely as possible to the true measure of programme effectiveness, which is the number of invasive cervical cancers and subsequent deaths prevented in the target population. The evaluation of benefits and adverse effects of each new suggested screening technology should be performed before the technology becomes an accepted routine in the existing screening programme. At best, the evaluation is performed randomised, within the population and screening programme in question, which makes the results directly applicable to routine use.

Modern computed tomography techniques in stroke management

Technological development of fast multi-sectional, helical computed tomography (CT) scanners has allowed computed tomography perfusion (CTp) and angiography (CTA) in evaluating acute ischemic stroke. This study focuses on new multidetector computed tomography techniques, namely whole-brain and first-pass CT perfusion plus CTA of carotid arteries. Whole-brain CTp data is acquired during slow infusion of contrast material to achieve constant contrast concentration in the cerebral vasculature. From these data quantitative maps are constructed of perfused cerebral blood volume (pCBV). The probability curve of cerebral infarction as a function of normalized pCBV was determined in patients with acute ischemic stroke. Normalized pCBV, expressed as a percentage of contralateral normal brain pCBV, was determined in the infarction core and in regions just inside and outside the boundary between infarcted and noninfarcted brain. Corresponding probabilities of infarction were 0.99, 0.96, and 0.11, R² was 0.73, and differences in perfusion between core and inner and outer bands were highly significant. Thus a probability of infarction curve can help predict the likelihood of infarction as a function of percentage normalized pCBV. First-pass CT perfusion is based on continuous cine imaging over a selected brain area during a bolus injection of contrast. During its first passage, contrast material compartmentalizes in the intravascular space, resulting in transient tissue enhancement. Functional maps such as cerebral blood flow (CBF), and volume (CBV), and mean transit time (MTT) are then constructed. We compared the effects of three different iodine concentrations (300, 350, or 400 mg/mL) on peak enhancement of normal brain tissue and artery and vein, stratified by region-of-interest (ROI) location, in 102 patients within 3 hours of stroke onset. A monotonic increasing peak opacification was evident at all ROI locations, suggesting that CTp evaluation of patients with acute stroke is best performed with the highest available concentration of contrast agent. In another study we investigated whether lesion volumes on CBV, CBF, and MTT maps within 3 hours of stroke onset predict final infarct volume, and whether all these parameters are needed for triage to intravenous recombinant tissue plasminogen activator (IV-rtPA). The effect of IV-rtPA on the affected brain by measuring salvaged tissue volume in patients receiving IV-rtPA and in controls was investigated also. CBV lesion volume did not necessarily represent dead tissue. MTT lesion volume alone can serve to identify the upper size limit of the abnormally perfused brain, and those with IV-rtPA salvaged more brain than did controls. Carotid CTA was compared with carotid DSA in grading of stenosis in patients with stroke symptoms. In CTA, the grade of stenosis was determined by means of axial source and maximum intensity projection (MIP) images as well as a semiautomatic vessel analysis. CTA provides an adequate, less invasive alternative to conventional DSA, although tending to underestimate clinically relevant grades of stenosis.