Cervical cancer screening history among women diagnosed with cervical cancer in Estonia 2017-18.

BACKGROUND: Despite the national cervical cancer screening programme launched in 2006, Estonia has one of the highest cervical cancer incidence rates in Europe. While the overall coverage of cervical cytology is high, the factors related to cancer screening history prior to cancer diagnosis need to be studied. METHODS: In this study, we aimed to examine the 10-year screening history of women diagnosed with cervical cancer in Estonia in 2017-18, using data collected from laboratory reports from 2007 to 2018. From each report, we extracted information on the date and result of cytology and on the laboratory where the sample was assessed. We analysed these data across cancer histology, the time interval between the last test result and cancer diagnosis and the laboratory type (local or regional). RESULTS: Among 319 women with cervical cancer, 181 (56.7%) did not have any cytology reports available. Among 138 women with at least one cytology, 60% had 1-3, 24% 4-6 and 16% ≥7 tests (mean 3.7) before cancer. In 78% of women, the last test was performed less than 5 years before cancer diagnosis and 62% of these tests did not report any abnormalities. The last cytology results differed significantly between the regional and local laboratories (P = 0.028). CONCLUSION: Women received the cervical cancer diagnosis in Estonia despite having several screening tests 10 years prior to the diagnosis. The proportion of cytology tests without any abnormalities less than 5 years before the diagnosis was worryingly high and needs further investigation together with the difference between laboratory types.

Quality Assessment of Cervical Cytology Practices in Estonia From 2007 to 2018.

BACKGROUND: Cervical cancer incidence and mortality in Estonia are among the highest in Europe, although the overall coverage with cervical cytology is high. This indicates potential issues with the quality of collection and/or laboratory evaluation of cervical cytology. OBJECTIVES: The aim of the retrospective observational study was to assess the quality of cervical cytology specimen collection, evaluation, and reporting using laboratory reports in Estonia. METHODS: The study included women with a cervical cancer diagnosis in 2017-2018. Cervical cytology and histology reports for these women in 2007-2018 were obtained from ten laboratories. We described the quality of cytology specimen collection and reporting of cytology results. Multivariate logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) to identify factors associated with NILM as the last cervical cytology result within 5 or 2 years before the cervical cancer diagnosis. Also, we calculated cytology-histology correlation (CHC). RESULTS: We identified 503 cytology and 100 histology reports from 138 women. The laboratories differed greatly regarding human resources, work capacity and volume. Differences between local and regional laboratories were observed in reporting specimen adequacy (P < .001). We found that local laboratories had 3 times higher odds (OR = 2.95, 95% CI: 1.05-8.33) of reporting normal results 2 years before cancer diagnosis than regional laboratories. According to the CHC, 58.9% of pairs were in agreement. CONCLUSIONS: The study showed considerable heterogeneity and suboptimal performance of cervical cytology practices in Estonia, particularly at local laboratories. Efforts to improve laboratory quality assurance are crucial.

Effect of Pap-smear and sociodemographic factors on cervical cancer risk in Estonia: A population-based case-control study.

BACKGROUND: Like many Eastern-European countries, Estonia struggles with ineffective cervical cancer (CC) screening. Despite a long-term organised screening programme and high overall Pap-smear coverage, CC incidence and mortality remain very high. The aim of the study was to examine the reasons for high CC incidence in Estonia by analysing the effect of Pap-smears and sociodemographic factors on CC risk. METHODS: In this population-based case-control study, women aged ≥ 25 years with an in situ/invasive CC diagnosed in Estonia in 2011-2017 were defined as cases. Using a density sampling scheme, controls were randomly selected from general population. To estimate CC risk associated with having no Pap-smears during seven years before diagnosis (cases) or index date (controls), place of residence, interruption in health insurance, and several sociodemographic factors, multivariate logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). Individual-level data from three population-based registries were used. RESULTS: Among 1439 cases and 4317 controls, proportion of women with no Pap-smears was 53% and 35%, respectively. Women with no Pap-smears were at higher risk for CC (OR=2.35; 95% CI: 1.85-2.98). CC risk was increased among women who were younger, living in more remote regions, lower-educated, or divorced/widowed. Interruption in health insurance was associated with a 23% risk increase. Regional differences in CC risk were observed among screened women. CONCLUSION: To reduce the risk of CC in Estonia, efforts are necessary to increase screening coverage among high-risk women and ensure the quality of CC screening programme. Screening approaches and communication should be tailored to the needs of different population groups. Further studies are warranted to identify the reasons for regional differences in CC risk.

Human papillomavirus self-sampling for long-term non-attenders in cervical cancer screening: A randomised feasibility study in Estonia.

OBJECTIVE: Organised cervical cancer screening was started in Estonia in 2006, but participation is still low. Human papillomavirus (HPV) self-sampling has proved to increase screening uptake. This study addressed the feasibility of HPV self-sampling and the acceptance of this method among long-term screening non-attenders. METHODS: A randomised intervention study was conducted in Estonia in 2020. Women born in 1958-1983 without a Pap smear in 2013-2019 were identified in the Estonian Health Insurance Fund database. From them, 12,000 women were randomly allocated to three equal-sized study groups. The opt-out group received a questionnaire and a Qvintip® sampling device by regular mail. Two opt-in groups received a questionnaire and an e-mail invitation to order a self-sampler online; one received Qvintip and the other Evalyn® Brush. Participants background characteristics were obtained from the Population Register. The effect of covariates on participation rate was estimated with multivariate Poisson regression. Acceptance of self-sampling was analysed according to agreement with statements in the questionnaire. RESULTS: The overall participation rate was 16% with significant differences between opt-out (26%) and opt-in (11%) groups. Compared to the opt-out Qvintip group, adjusted relative risks for the Qvintip and Evalyn Brush opt-in groups were 0.41 (95% confidence interval (CI) 0.37-0.45) and 0.44 (95% CI 0.40-0.49), respectively. Participation was associated with living place, citizenship, and education. Self-sampling was well accepted: 98% agreed that it was easy to use, 88% preferred it as a screening method in future. CONCLUSIONS: The results show the feasibility and good acceptance of HPV self-sampling among long-term screening non-attenders in Estonia.

The EU-TOPIA evaluation tool: An online modelling-based tool for informing breast, cervical, and colorectal cancer screening decisions in Europe.

BACKGROUND: Aiming to support European countries in improving their breast, cervical, and colorectal cancer (CRC) screening programmes, the EU-TOPIA consortium has developed an online user-friendly tool (the EU-TOPIA evaluation tool; https://miscan.eu-topia.org) based on the Microsimulation Screening Analysis (MISCAN) model. METHODS: We designed an online platform that allows stakeholders to use their country-specific data (demographic, epidemiological, and cancer screening information) to quantify future harms and benefits of different cancer screening scenarios in their country. Current cancer screening programmes and impacts of potential changes in screening protocols (such as extending target ages or increasing screening attendance) can be simulated. Results are scaled to the country-specific population. To illustrate the tool, we used the tool to simulate two different CRC screening scenarios in the Netherlands: biennial fecal immunochemical testing (FIT) in ages 55-75 and colonoscopy every ten years in ages 55-75. Data from the Dutch screening programme was used to inform both scenarios. RESULTS: A total of 482,700 CRC cases and 178,000 CRC deaths were estimated in the Netherlands with FIT screening (for individuals aged 40-100 years, 2018-2050), with 47.3 million FITs performed (1.92 million positives of which 1.64 million adhered to diagnostic colonoscopy). With colonoscopy screening, CRC incidence and mortality were, respectively, up to 17% and 14% lower than in the current FIT screening programme, requiring, however, a colonoscopy demand that was 7-fold higher. CONCLUSIONS: Our study presents an essential online tool for stakeholders and medical societies to quantify estimates of benefits and harms of early cancer detection in Europe.

Cervical cancer screening patterns among HIV-positive women in Estonia: a population-based retrospective cohort study.

BACKGROUND: The World Health Organisation (WHO) calls for the elimination of cervical cancer (CC) as a public health issue. To achieve elimination, efforts must be aligned and accelerated. Women living with HIV (WLWH) have excess risk for developing, and dying from, CC over the general population. Estimates of cervical cancer screening programme coverage in Eastern European countries that have experienced HIV epidemics since the early 2000's are scarce. METHOD: This population-based retrospective study uses a healthcare administrative database and follows cohorts of all WLWH in a ratio of 1:3 randomly matched (age, region) HIV negative women from 2009 to 2018. Annual and longitudinal (over the whole study period) coverage for cervical cancer screening (opportunistic, organised, HIV specific) and adjusted odds ratios (AORs) for longitudinal screening coverage predictors were estimated from 2009 to 2018. RESULTS: Among WLWH and HIV-negative women, the mean annual coverage with opportunistic screening was 61.45 and 65.59%; and organised screening was 20.4 and 28.7%, respectively (both: p < 0.00001). 19.01% (95% CI 18.05-19.97) HIV-negative and 13.9% (95% CI 12.35-15.45) WLWH were longitudinally covered with organised cervical cancer screening. Among WLWH, the mean annual HIV-specific cervical cancer screening coverage was 49.4, and 24.3% were longitudinally covered. Longitudinal coverage with HIV-specific cervical cancer screening was inversely associated with age, hepatitis C virus (HCV) co-infection (AOR 0.754, 95% CI 0.619, 0.916), not having insurance (AOR 0.331, 95% CI 0.264, 0.412), drug abuse (AOR 0.459, 95% CI 0.336, 0.618) and higher among those retained in HIV care (AOR 1.972, 95% CI 1.615, 2.410). Among HIV-negative women, longitudinal coverage with organised cervical cancer screening was inversely associated with residence in the region and higher among older women. CONCLUSIONS: Our results highlight unacceptably low coverage of cervical cancer screening of WLWH in Estonia. There is need for dedicated cervical cancer screening efforts for WLWH considering the high cancer risk and rate in the study population.

Development and Validation of Three Regional Microsimulation Models for Predicting Colorectal Cancer Screening Benefits in Europe.

Background. Validated microsimulation models have been shown to be useful tools in providing support for colorectal cancer (CRC) screening decisions. Aiming to assist European countries in reducing CRC mortality, we developed and validated three regional models for evaluating CRC screening in Europe. Methods. Microsimulation Screening Analysis-Colon (MISCAN-Colon) model versions for Italy, Slovenia, and Finland were quantified using data from different national institutions. These models were validated against the best available evidence for the effectiveness of screening from their region (when available): the Screening for COlon REctum (SCORE) trial and the Florentine fecal immunochemical test (FIT) screening study for Italy; the Norwegian Colorectal Cancer Prevention (NORCCAP) trial and the guaiac fecal occult blood test (gFOBT) Finnish population-based study for Finland. When published evidence was not available (Slovenia), the model was validated using cancer registry data. Results. Our three models reproduced age-specific CRC incidence rates and stage distributions in the prescreening period. Moreover, the Italian and Finnish models replicated CRC mortality reductions (reasonably) well against the best available evidence. CRC mortality reductions were predicted slightly larger than those observed (except for the Florentine FIT study), but consistently within the corresponding 95% confidence intervals. Conclusions. Our findings corroborate the MISCAN-Colon reliability in supporting decision making on CRC screening. Furthermore, our study provides the model structure for an additional tool (EU-TOPIA CRC evaluation tool: http://miscan.eu-topia.org) that aims to help policymakers and researchers monitoring or improving CRC screening in Europe.

The potential of breast cancer screening in Europe.

Currently, all European countries offer some form of breast cancer screening. Nevertheless, disparities exist in the status of implementation, attendance and the extent of opportunistic screening. As a result, breast cancer screening has not yet reached its full potential. We examined how many breast cancer deaths could be prevented if all European countries would biennially screen all women aged 50 to 69 for breast cancer. We calculated the number of breast cancer deaths already prevented due to screening as well as the number of breast cancer deaths which could be additionally prevented if the total examination coverage (organised plus opportunistic) would reach 100%. The calculations are based on total examination coverage in women aged 50 to 69, the annual number of breast cancer deaths for women aged 50 to 74 and the maximal possible mortality reduction from breast cancer, assuming similar effectiveness of organised and opportunistic screening. The total examination coverage ranged from 49% (East), 62% (West), 64% (North) to 69% (South). Yearly 21 680 breast cancer deaths have already been prevented due to mammography screening. If all countries would reach 100% examination coverage, 12 434 additional breast cancer deaths could be prevented annually, with the biggest potential in Eastern Europe. With maximum coverage, 23% of their breast cancer deaths could be additionally prevented, while in Western Europe it could be 21%, in Southern Europe 15% and in Northern Europe 9%. Our study illustrates that by further optimising screening coverage, the number of breast cancer deaths in Europe can be lowered substantially.

Evidence for reducing cancer-specific mortality due to screening for breast cancer in Europe: A systematic review.

BACKGROUND: The aim of this study was to quantify the impact of organised mammography screening on breast cancer mortality across European regions. Therefore, a systematic review was performed including different types of studies from all European regions and stringently used clearly defined quality appraisal to summarise the best evidence. METHODS: Six databases were searched including Embase, Medline and Web of Science from inception to March 2018. To identify all eligible studies which assessed the effect of organised screening on breast cancer mortality, two reviewers independently applied predefined inclusion and exclusion criteria. Original studies in English with a minimum follow-up of five years that were randomised controlled trials (RCTs) or observational studies were included. The Cochrane risk of bias instrument and the Newcastle-Ottawa Scale were used to assess the risk of bias. RESULTS: Of the 5015 references initially retrieved, 60 were included in the final analysis. Those comprised 36 cohort studies, 17 case-control studies and 7 RCTs. None were from Eastern Europe. The quality of the included studies varied: Nineteen of these studies were of very good or good quality. Of those, the reduction in breast cancer mortality in attenders versus non-attenders ranged between 33% and 43% (Northern Europe), 43%-45% (Southern Europe) and 12%-58% (Western Europe). The estimates ranged between 4% and 31% in invited versus non-invited. CONCLUSION: This systematic review provides evidence that organised screening reduces breast cancer mortality in all European regions where screening was implemented and monitored, while quantification is still lacking for Eastern Europe. The wide range of estimates indicates large differences in the evaluation designs between studies, rather than in the effectiveness of screening.

Increasing incidence and survival of corpus uteri cancer in Estonia over the past two decades.

BACKGROUND: Corpus uteri cancer has become the fourth most common female cancer in Europe. In Estonia, the prevalence of obesity is increasing, and corpus uteri cancer survival has been relatively low. The aim of the study was to evaluate incidence, mortality and survival trends of corpus uteri cancer in Estonia by age, stage and histological subtypes with an emphasis on surgical treatment. METHODS: Estonian Cancer Registry data on incident cases of corpus uteri cancer were used to examine incidence trends (1995-2016) and calculate relative survival ratios (RSR) (1996-2016). Cases were classified by morphology and FIGO stage. Causes of Death Registry data were used to analyse corrected mortality (1995-2017). RESULTS: A total of 4281 cases were diagnosed in 1996-2016. A significant increase was seen in age-standardized incidence from 2009, while mortality remained stable throughout the study period. Significant increases were observed for type I cancers and age groups ≥65 years. Overall age-standardized 5-year RSR improved from 70% in 1996-2002 to 78% in 2010-2016. Survival increased for type I cancers, all age groups and all stages (significantly for stage IV). The proportion of surgically treated cases increased significantly from 85% to 89%, with the largest increases seen in older age groups and later stages. DISCUSSION: The rising corpus uteri cancer incidence in Estonia is driven by the type I cancer trend. Survival gain for later stages and older age groups likely reflected more frequent surgical treatment. To reduce mortality, further efforts are necessary to ensure appropriate care for all patients.

A case report and follow-up of the first live birth after heterotopic transplantation of cryopreserved ovarian tissue in Eastern Europe.

BACKGROUND: Ovarian insufficiency is a major concern for long-term cancer survivors. Although semen freezing is well established to preserve male fertility, the possibilities to secure post-cancer female fertility are mostly limited to oocyte or embryo freezing. These methods require time-consuming ovarian stimulation with or without in vitro fertilization (IVF) that evidently delays cancer therapy. Ovarian tissue cryopreservation and subsequent thawed tissue autotransplantation are considered the most promising alternative strategy for restoring the fertility of oncology patients, which has not yet received the full clinical acceptance. Therefore, all successful cases are needed to prove its reliability and safety. CASE PRESENTATION: Here we report a single case in Estonia, where a 28-year-old woman with malignant breast neoplasm had ovarian cortex cryopreserved before commencing gonadotoxic chemo- and radiotherapy. Two years after cancer therapy, the patient underwent heterotopic ovarian tissue transplantation into the lateral pelvic wall. The folliculogenesis was stimulated in the transplanted tissue by exogenous follicle-stimulating hormone and oocytes were collected under ultrasound guidance for IVF and embryo transfer. The healthy boy was born after full-term gestation in 2014, first in Eastern Europe. CONCLUSION: Despite many countries have reported the first implementation of the ovarian tissue freezing and transplantation protocols, the data is still limited on the effectiveness of heterotopic ovarian transplant techniques. Thus, all case reports of heterotopic ovarian tissue transplantation and long-term follow-ups to describe the children's health are valuable source of clinical experience.

NordScreen - an interactive tool for presenting cervical cancer screening indicators in the Nordic countries.

Introduction: Quality assurance and improvement of cancer screening programs require up-to-date monitoring systems and evidence-based indicators. National quality reports exist but the definition and calculation of indicators vary making comparisons between countries difficult. The aim is to stimulate collaborative research and quality improvements in screening through freely available, comparable and regularly updated quality indicators. The project currently includes data on cervical cancer screening but population-based screening programs for breast cancer and colorectal cancer may be included in the future. Material and methods: Through a network of Nordic and Baltic screening managers, population-based individual screening data from each country were converted to standard format in each collaborative center, aggregated by the same R program script and then uploaded to the NordScreen online platform. Registry data included all cervical tests except for Finland where only tests based on invitation are included. Results: The NordScreen collaboration has so far collated standardized indicators based on 32.8 million screening tests from four Nordic countries and Estonia. Interactive comparison of test coverage and distribution of women by number of tests are currently possible online. In 2016, the test coverage within a time interval of 5.5 years in the age group 30-64 year-olds was between 78 and 84% in Iceland, Norway and Sweden whereas 70% in Finland. The application allows users to choose indicator specifications interactively. Conclusions: NordScreen is a pilot model for comparable, reliable and accessible cross-country comparisons of cancer screening. Comparability between countries is enhanced by a uniform data structure and standardized calculations. The comparison of coverage rates to national figures shows that the methods used nationally and in the NordScreen project produce similar results.

Trends in cervical cancer incidence and survival in Estonia from 1995 to 2014.

BACKGROUND: Cervical cancer (CC) incidence in Estonia is the third highest in Europe, even though an organised nation-wide screening program has been in place since 2006. The aim of the study was to analyse the incidence and survival of CC in Estonia, focusing on age, morphology and stage at diagnosis. METHODS: Data from Estonian Cancer Registry were used to analyse age-standardized (world) and age-specific incidence for 1968-2014 rates. Joinpoint regression was used to estimate the annual percentage change (APC) for incidence trends. Age-period-cohort model was used to summarise time trends in terms of cohort and period effects. Relative survival ratios (RSR) were calculated for cases diagnosed in 1995-2014. Union for International Cancer Control version 7 of the TNM classification for malignant tumours was used to categorise stage. RESULTS: The age-standardized incidence of CC increased since 1980s at a rate of 0.8% per year. A significant increase was seen for all age groups except for 70+. The incidence of squamous cell carcinoma mimicked the overall trend, while adenocarcinoma showed increase since mid-1990s (APC 6.7). Age-period-cohort modelling showed strong cohort effects with the lowest risk for birth-cohorts born around 1940 and significantly increasing risks for successive cohorts born thereafter. No period effects were seen. The proportion of stage IV cases increased from 13% in 2005-2009 to 18% in 2010-2014. A significant increase was seen in the overall 5-year RSR from 1995 to 1999 to 2010-2014 (58% vs 66%). In 2010-2014, the 5-year RSRs ranged from 89% in women aged 15-39 to 41% in age group 70+. For stages I to IV, the respective RSRs were 98, 74, 57 and 22%. CONCLUSIONS: The inadequate uptake and insufficient quality of the Pap-smear based screening program has not brought along a decline in the incidence of CC in Estonia. Stage distribution has shifted towards later stages. New approaches are needed to prevent CC in Estonia.

A health systems approach to identifying barriers to breast cancer screening programmes. Methodology and application in six European countries.

The benefits of population-based screening for breast cancer are now accepted although, in practice, programmes often fail to achieve their full potential. In this paper, we propose a conceptual model that situates screening programmes within the broader health system to understand the factors that influence their outcomes. We view the overall screening system as having multiple sub-systems to identify the population at risk, generate knowledge of effectiveness, maximise uptake, operate the programme, and optimise follow-up and assurance of subsequent treatment. Based on this model we have developed the Barriers to Effective Screening Tool (BEST) for analysing government-led, population-based screening programmes from a health systems perspective. Conceived as a self-assessment tool, we piloted the tool with key informants in six European countries (Estonia, Finland, Hungary, Italy, The Netherlands and Slovenia) to identify barriers to the optimal operation of population-based breast cancer screening programmes. The pilot provided valuable feedback on the barriers affecting breast cancer screening programmes and stimulated a greater recognition among those operating them of the need to take a health systems perspective. In addition, the pilot led to further development of the tool and provided a foundation for further research into how to overcome the identified barriers.

Results of a health systems approach to identify barriers to population-based cervical and colorectal cancer screening programmes in six European countries.

The aim of this study was to identify barriers to effective cervical and colorectal cancers screening programmes in Europe. The Barriers to Effective Screening Tool (BEST), based on a health systems approach, was completed by teams of three to six experts on cancer screening in each of the six countries involved in leading the EU-TOPIA project (TOwards imProved screening for breast, cervical and colorectal cancer In All of Europe). While the basic components of screening systems and the challenges they face, such as low participation, are similar, there are also many differences, both in the structures underpinning particular functions, such as maintenance of populationregisters and monitoring outcomes, and the ways that they operate. Many of these lie outside the strict organisational boundaries of screening programmes. BEST offers a means to identify and prioritise issues for further detailed exploration. The holistic health systems approach to assessing barriers differs from previous approaches. Those focus on individual characteristics that determine participation. The approach described here provides additional opportunities to improve outcomes with measures that are largely within the control of those managing the health system.

Time Trends in Ovarian Cancer Survival in Estonia by Age and Stage.

OBJECTIVE: The objective of the study was to examine temporal trends in ovarian cancer (OC) survival in Estonia during 1995 to 2009 in relation to age and stage. MATERIALS AND METHODS: Estonian Cancer Registry data on all adult cases of primary OC diagnosed during 1995 to 2009 and followed up for vital status until 2014 were used to estimate relative survival ratios (RSRs). Cohort analysis was used to estimate 1-, 2-, and 5-year RSRs for patients diagnosed in 1995 to 1999, 2000 to 2004, and 2005 to 2009. Analysis was performed by age at diagnosis (<50; 50-59; 60-69; 70+ years) and stage (International Federation of Gynecology and Obstetrics 1988). RESULTS: Among 2296 women included in the study, the age-adjusted 5-year RSR improved from 27% in 1995 to 1999 to 38% in 2005 to 2009. Survival increase of 10% units from 1995 to 1999 to 2005 to 2009 was seen for women aged 50 to 59 and 60 to 69 years. Among younger and older women, the respective changes were smaller. In 1995 to 1999, the difference in survival between the youngest and oldest age groups was 41% units. This decreased over the study period to 37% units. From 1995 to 1999 to 2005 to 2009, the 5-year RSR increased from 82% to 91% for stage I patients; from 48% to 67% for stage II patients; from 25% to 35% for stage III patients; and from 11% to 16% for stage IV patients. CONCLUSIONS: The study showed an improvement of OC survival in Estonia in all age and stage groups, but particularly among younger women and those with early stage disease. Slower progress among older women is of great concern.

Effect of characteristics of women on attendance in blind and non-blind randomised trials: analysis of recruitment data from the EPHT Trial.

OBJECTIVES: To analyse the effect of women's characteristics on their willingness to join a blind or a non-blind subtrial or to be excluded by physicians. DESIGN: Primary prevention trial of postmenopausal hormone therapy (HT). A 2×2, randomised design with a non-blind HT arm or control arm and a blind HT arm or placebo arm. SETTING: 3 clinical centres in Estonia. METHODS: Interest in joining the trial was asked in a questionnaire together with demographic and health status data. Interested and eligible women were invited to a health examination that also informed whether they belonged to a blind or to a non-blind subtrial; the arm was not revealed. Trial physicians made further exclusions when checking the women's eligibility. Thereafter, informed consent was asked as detailed in the flow chart. Comparisons were made between non-blind and blind subtrials. Analyses were carried out for each of the background variables. OUTCOME MEASURES: The proportion of willingness, eligibility and attendance. RESULTS: Women randomised to the non-blind subtrial were more willing to join (relative risk (RR) 1.17) and more likely to be found eligible by physicians (RR 1.10) than women in the blind subtrial, resulting in larger attendance (RR 1.29). Women with higher education were differentially more willing to join the non-blind trial (RR 1.29) than those with basic education (RR 1.08); the differential willingness of never-smokers (RR 1.20) was larger than that of current smokers (RR 1.07). The differential exclusion by physicians by education and smoking were small. Some subjective symptoms (eg, diarrhoea/constipation, stomach pain) had reverse differential effects on attendance in the non-blind subtrial in comparison to the blind subtrial. Menopausal symptoms did not affect the differential interest, eligibility or attendance. CONCLUSIONS: Blinding in RCT reduces attendance, due to decisions of the women and the trial physicians. Differential attendance by blinding may affect the generalisability of the results from trials. TRIAL REGISTRATION NUMBER: ISRCTN35338757.

Preventable fractions of cervical cancer via effective screening in six Baltic, central, and eastern European countries 2017-40: a population-based study.

BACKGROUND: Cervical cancer incidence remains high in several Baltic, central, and eastern European (BCEE) countries, mainly as a result of a historical absence of effective screening programmes. As a catalyst for action, we aimed to estimate the number of women who could be spared from cervical cancer across six countries in the region during the next 25 years, if effective screening interventions were introduced. METHODS: In this population-based study, we applied age-period-cohort models with spline functions within a Bayesian framework to incidence data from six BCEE countries (Estonia, Latvia, Lithuania, Belarus, Bulgaria, and Russia) to develop projections of the future number of new cases of cervical cancer from 2017 to 2040 based on two future scenarios: continued absence of screening (scenario A) versus the introduction of effective screening from 2017 onwards (scenario B). The timespan of available data varied from 16 years in Bulgaria to 40 years in Estonia. Projected rates up to 2040 were obtained in scenario A by extrapolating cohort-specific trends, a marker of changing risk of human papillomavirus (HPV) infection, assuming a continued absence of effective screening in future years. Scenario B added the effect of gradual introduction of screening in each country, under the assumption period effects would be equivalent to the decreasing trend by calendar year seen in Denmark (our comparator country) since the progressive regional introduction of screening from the late 1960s. FINDINGS: According to scenario A, projected incidence rates will continue to increase substantially in many BCEE countries. Very high age-standardised rates of cervical cancer are predicted in Lithuania, Latvia, Belarus, and Estonia (up to 88 cases per 100 000). According to scenario B, the beneficial effects of effective screening will increase progressively over time, leading to a 50-60% reduction of the projected incidence rates by around 2040, resulting in the prevention of cervical cancer in 1500 women in Estonia and more than 150 000 women in Russia. The immediate launch of effective screening programmes could prevent almost 180 000 new cervical cancer diagnoses in a 25-year period in the six BCEE countries studied. INTERPRETATION: Based on our findings, there is a clear need to begin cervical screening in these six countries as soon as possible to reduce the high and increasing incidence of cervical cancer over the next decades. FUNDING: None.

Population health and status of epidemiology in Western European, Balkan and Baltic countries.

BACKGROUND: This article is part of a series commissioned by the International Epidemiological Association, aimed at describing population health and epidemiological resources in the six World Health Organization (WHO) regions. It covers 32 of the 53 WHO European countries, namely the Western European countries, the Balkan countries and the Baltic countries. METHODS: The burdens of mortality and morbidity and the patterns of risk factors and inequalities have been reviewed in order to identify health priorities and challenges. Literature and internet searches were conducted to stock-take epidemiological teaching, research activities, funding and scientific productivity. FINDINGS: These countries have among the highest life expectancies worldwide. However, within- and between-country inequalities persist, which are largely due to inequalities in distribution of main health determinants. There is a long tradition of epidemiological research and teaching in most countries, in particular in the Western European countries. Cross-national networks and collaborations are increasing through the support of the European Union which fosters procedures to standardize educational systems across Europe and provides funding for epidemiological research through framework programmes. The number of Medline-indexed epidemiological research publications per year led by Western European countries has been increasing. The countries accounts for nearly a third of the global epidemiological publication. CONCLUSIONS: Although population health has improved considerably overall, persistent within- and between-country inequalities continue to challenge national and European health institutions. More research, policy and action on the social determinants of health are required in the region. Epidemiological training, research and workforce in the Baltic and Balkan countries should be strengthened. European epidemiologists can play pivotal roles and must influence legislation concerning production and access to high-quality data.