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Comparable performance indicators for breast cancer screening in the European Union (EU) have not been previously reported. We estimated adjusted breast cancer screening positivity rate (PR) and detection rates (DR) to investigate variation across EU countries. For the age 50-69 years, the adjusted EU-pooled PR for initial screening was 8.9% (cross-programme variation range 3.2-19.5%) while DR of invasive cancers was 5.3/1,000 (range 3.8-7.4/1,000) and DR of ductal carcinoma in situ (DCIS) was 1.3/1,000 (range 0.7-2.7/1,000). For subsequent screening, the adjusted EU-pooled PR was 3.6% (range 1.4-8.4%), the DR was 4.0/1,000 (range 2.2-5.8/1,000) and 0.8/1,000 (range 0.5-1.3/1,000) for invasive and DCIS, respectively. Adjusted performance indicators showed remarkable heterogeneity, likely due to different background breast cancer risk and awareness between target populations, and also different screening protocols and organisation. Periodic reporting of the screening indicators permits comparison and evaluation of the screening activities between and within countries aiming to improve the quality and the outcomes of screening programmes. Cancer Screening Registries would be a milestone in this direction and EU Screening Reports provide a fundamental contribution to building them.

BACKGROUND The objective of this study was to describe the determinants of adequacy and positivity of the p16/Ki-67 assay in a human papillomavirus (HPV)-positive screening population enrolled within the New Technologies for Cervical Cancer 2 (NTCC2) study. METHODS ThinPrep slides were immunostained for p16/Ki-67; each slide had 3 reports from different laboratories. The authors included population-related, sampling-related/staining-related, and interpretation-related variables in the analyses. Adequacy and positivity proportions were stratified by variables of interest. Univariate and multivariate logistic models were used to identify determinants of adequacy and positivity. RESULTS In total, 3100 consecutive HPV-positive cases were analyzed. Because every slide was interpreted by 3 centers, 9300 reports were obtained, including 905 (9.7%) that were inadequate and 2632 (28.3%) that were positive. The percentage of cases in which all 3 reports were inadequate increased with increasing age of the women and with inadequate cytology. The highest percentage of adequacy in all 3 reports and of cases with all 3 reports positive was observed in specimens from women who had grade ≥2 cervical intraepithelial neoplasia (CIN2+), atypical squamous cells of undetermined significance or more severe (ASC-US+) cytology, or mRNA positivity. The number of inadequate reports was significantly associated with increasing age, inadequate cytology, mRNA negativity, and scant cellularity. A positive p16/Ki-67 report was associated with an ASC-US+ result and with a positive mRNA result in cases both with and without CIN2+ but was associated with an HPV type 16 and/or 18 infection only in CIN2+ cases. The presence of CIN2+ was strongly associated with dual staining positivity. CONCLUSIONS The interpretation of p16/Ki-67 results may be influenced by several different variables, all of which are part of the steps in the procedure, and by the characteristics of the screened population.

ObjectiveTo present comparative data about the performance of colorectal cancer (CRC) screening programmes in the European Union Member States (EU MSs).DesignCross-sectional study. We analysed key performance indicators—participation rate, positivity rate (PR), detection rate (DR) and positive predictive value for adenomas and CRC—based on the aggregated quantitative data collected for the second EU screening report. We derived crude and pooled (through a random effects model) estimates to describe and compare trends across different MSs/regions and screening protocols.ResultsParticipation rate was higher in countries adopting faecal immunochemical test (FIT) (range: 22.8%–71.3%) than in those using guaiac faecal occult blood test (gFOBT) (range 4.5%–66.6%), and it showed a positive correlation (ρ=0.842, pConclusionsThe variability in the results of quality indicators across population-based screening programmes highlights the importance of continuous monitoring, as well as the need to promote quality improvement efforts, as recommended in the EU guidelines. The implementation of monitoring systems, ensuring availability of data for the entire process, together with initiatives aimed to enhance reproducibility of histology and quality of endoscopy, represent a priority in screening programmes management.

Cervical cancer screening will rely, increasingly, on HPV testing as a primary screen. The requirement for triage tests which can delineate clinically significant infection is thus prescient. In this EUROGIN 2017 roadmap, justification behind the most evidenced triages is outlined, as are challenges for implementation. Cytology is the triage with the most follow-up data; the existence of an HR-HPV positive, cytology negative group presents a challenge and re-testing intervals for this group (and choice of re-test) require careful consideration. Furthermore, cytology relies on subjective skills and while adjunctive dual-staining with p16/Ki67 can mitigate inter-operator/site disparities, clinician-taken samples are required. Comparatively, genotyping and methylation markers are objective and are applicable to self-taken samples, offering logistical advantages including in low and middle income settings. However, genotyping may have diminishing returns in immunised populations and type(s) included must balance absolute risk for disease to avoid low specificity. While viral and cellular methylation markers show promise, more prospective data are needed in addition to refinements in automation. Looking forward, systems that detect multiple targets concurrently such as next generation sequencing platforms will inform the development of triage tools. Multi-step triage strategies may be be beneficial provided they do not create complex, unmanageable pathways. Inevitably, the balance of risk to cost(s) will be key in decision making, although defining an acceptable risk will likely differ between settings. Finally, given the significant changes to cervical screening and the variety of triage strategies, appropriate education of both health care providers and the public is essential.

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.

In a screening programme for cervical cancer, coverage of the target population is a major determinant of effectiveness and cost-effectiveness and is one of the parameters for programme monitoring recommended by the "European Guidelines for Quality Assurance". An organised screening programme was started in Turin, Italy, in 1992. Spontaneous screening was already largely present, but coverage (proportion of women who had at least a test within 3 years) was low (50%) and distribution of smears uneven. No comprehensive registration of spontaneous smears was available. All women were invited for the first round, independently of their previous test history. Coverage was estimated by integrating routine data from the organised programme with data on spontaneous screening obtained by interviews of a random sample of 268 non-compliers to invitation and 167 compliers. Overall (spontaneous + organised) coverage was estimated to be 74% (95% CI, 71-78%). The proportion of the target population covered as an effect of invitation was estimated to be 17% (95% CI, 15-20%). Invitations were successful in increasing coverage in previously poorly screened groups. Although 20-25% of compliers was estimated to have had further tests before the end of the round, we estimated that switching to a 3-year interval saved approximately 0.26 tests per complier. This suggests that invitations to an organised programme even to previously covered women, can be a cost-effective policy. Our method of estimating overall coverage can be useful in many other European areas where a comprehensive registration of smears is not available.

Objectives To evaluate screening patterns within organized cervical screening programs (OCSPs) and survival of women with invasive cervical cancer (ICC). Methods A population-based study was conducted in Italian areas covered by cancer registries and OCSPs. The study included all women aged 25–65 years diagnosed with ICC between 1995 and 2008, and their screening histories within OCSPs were retrieved. Hazard ratios (HR) of death and 95% confidence intervals (CI) were computed according to screening pattern, using Cox models adjusted for age, ICC stage, and major confounders. Results Among 3268 women with ICC, 20% were never-invited to OCSP, 36% were never-compliant with OCSP's invitation, 33% were compliant and had a screen-detected ICC within OCSP (i.e., after a positive cytology), and 11% were compliant but had a non-screen-detected ICC. Screen-detected ICCs were more frequently micro-invasive (42%) compared to non-screen-detected ones (14%). Compared to women with screen-detected ICC, the adjusted HRs of death were 1.9 (95% CI 1.5–2.4) for those never-invited, 2.0 (95% CI 1.6–2.5) for never-compliant, and 1.7 (95% CI 1.3–2.4) for compliant women having non-screen-detected ICC. Conclusion Prolonged survival, beyond down-staging, of women with ICC detected within OCSPs in Italy, further calls for improvements of OCSPs' invitational coverage and participation.

Our results demonstrate that saccharidic derivatives obtained by adding a C8 alkyl group through various heteroatomes (O, N or S) to a monoacetonide residue possess an inhibitory effect towards putative P-type calcium channels expressed in Xenopus oocytes. These derivatives partially and reversibly inhibit the activity of these channels without changing their electrophysiological properties. Nevertheless, the derivative containing the heteroatome N also affects the fast and tetrodotoxin-sensitive sodium channel activity. Thus, only ether and thioether compounds (heteroatome O or S) can be selected for their inhibitory effect on P-type apparented calcium channels.

Aims and background Attendance level has been identified as a major determinant of cost-effectiveness of organized screening programs. We tested the effectiveness of 4 different invitation systems in the context of an organized population screening program for cervical and breast cancer. Methods Women eligible for invitation - 8385 for cervical and 8069 for breast cancer screening - listed in the rosters of 43 and 105 general practitioners (GP), respectively, who had accepted to collaborate in the program, were randomized to 4 invitation groups: Group A - letter signed by the GP, with a prefixed appointment; Group B - open-ended invitation, signed by the GP, prompting women to contact the screening center to arrange an appointment; Group C - letter (same as for group A), signed by the program coordinator, with a prefixed appointment; Group D - extended letter (highlighting the benefits of early cancer detection) signed by the GP, with a prefixed appointment. Assignment to the interventions was based on a randomized block design (block=GP). Results Assuming Group A as the reference, the overall compliance with cervical cancer screening was reduced by 39% in Group B (RR=0.61; 95% CI, 0.56-0.68) and by 14% in Group C (RR=0.86; 95% CI, 0.78-0.93); no difference was observed for Group D (RR=1.03; 95% CI, 0.95-1.1). The response pattern was similar for breast screening (Group B: RR=0.71; 95% CI, 0.65-0.76; Group C: RR=0.87; 95% CI, 0.81-0.94; Group D: RR=1.01; 95% CI, 0.94-1.08). Conclusions Personal invitation letters signed by the woman's GP, with preallocated appointments, induce a significant increase in compliance with screening. Efficiency can be ensured through the adoption of overbooking, provided that attendance levels are regularly monitored.