Piret Veerus

Process performance of cervical screening programmes in Europe

Standardised tables of aggregated data were collected from 15 European national or regional cervical screening programmes and key performance indicators computed as reported in European Union (EU) Guidelines, 2nd edition. Cytological results varied widely between countries both for the total proportion of abnormal tests (from 1.2% in Germany (Mecklenburg-Vorpommern) to 11.7% in Ireland-Midwest Region) and for their distribution by grade. Referral rates for repeat cytology (ranging from 2.9% of screened women in the Netherlands to 16.6% in Slovenia) or for colposcopy (ranging from 0.8% in Finland to 4.4% in Romania-Cluj) and the Positive Predictive Value (PPV) of colposcopic attendance (ranging from 8% in Romania-Cluj to 52% in Lithuania) were strongly influenced by management protocols, in particular for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology. However, cytology-specific PPV also showed remarkable variability. The detection rate of CIN2+ histology ranged from <0.1% of screened women in Poland to >1% in England and Denmark. Low attendance for colposcopy after referral was observed in some east-European countries. These comparisons may be useful for improving the performance of cervical screening in general and more so if new screening technologies and vaccination for Human Papillomavirus are introduced. Overall, quality was better in countries that have operated organised programmes for a longer time, plausibly as a result of long-lasting monitoring and quality assurance activities. Therefore, the availability of these data, the first comparing European countries, and the increased number of countries that can provide such data (only five in 2004) represent progress. Nevertheless, there is a clear need to standardise the cytological and histological classifications used in screening, as well as data registration systems across Europe.

Women's knowledge about cervical cancer risk factors, screening, and reasons for non-participation in cervical cancer screening programme in Estonia

BackgroundThe attendance rate in Estonian cervical cancer screening programme is too low therefore the programme is hardly effective. A cross-sectional population based survey was performed to identify awareness of cervical cancer risk factors, reasons why women do not want to participate in cervical screening programme and wishes for better organisation of the programme.MethodAn anonymous questionnaire with a covering letter and a prepaid envelope was sent together with the screening invitation to 2942 randomly selected women. Results are based on the analysis of 1054 (36%) returned questionnaires.ResultsMain reasons for non-participation in the national screening programme were a recent visit to a gynaecologist (42.3%), fear to give a Pap-smear (14.3%), long appointment queues (12.9%) and unsuitable reception hours (11.8%). Fear to give a Pap-smear was higher among women aged 30 and 35 than 50 and 55 (RR 1.46; 95% CI: 0.82-2.59) and women with one or no deliveries (RR 1.56, 95% CI: 0.94-2.58). In general, awareness of cervical cancer risk factors is poor and it does not depend on socio-demographic factors. Awareness of screening was higher among Estonians than Russians (RR 1.64, 95% CI: 1.46-1.86). Most women prefer to receive information about screening from personally mailed invitation letters (74.8%).ConclusionsWomen need more information about cervical cancer risk factors and the screening programme. They prefer personally addressed information sharing. Minority groups should be addressed in their own language. A better collaboration with service providers and discouraging smears outside the programme are also required.

Legislative regulation and ethical governance of medical research in different European Union countries

Objective To obtain information about the similarities and differences in regulating different types of medical research in the European Union (EU). Methods Web searches were performed from September 2009 to January 2011. Notes on pre-determined topics were systematically taken down from the web pages. The analysis relied only on documents and reports available on the web, reflecting the situation at the end of 2010. Results In several countries, regulatory legislation applied only to clinical trials on drugs and medical devices, in other states various types of research were also regulated but by laws different from those concerning trials, and in many countries, some research areas were not controlled by legislation at all. In very few countries was all medical research handled similarly from a legal point of view. The number of research ethics committees (RECs) in a single country varied from one to 264. Their areas of responsibility, working principles and length of time to grant research permission varied as well as the rules for obtaining informed consent from vulnerable groups. In 10 EU countries, there was no appeal mechanism after a negative decision by an REC. The RECs were not accountable to any organisation in five EU countries. Conclusions There is a need for a fundamental debate regarding whether and which kinds of changes are needed for the further harmonisation of medical research governance in the EU and how cross-country medical research could be facilitated in the future.

Symptom reporting and quality of life in the Estonian Postmenopausal Hormone Therapy Trial

BackgroundThe aim of the study was to determine the effect of postmenopausal hormone therapy on womens symptom reporting and quality of life in a randomized trial.Methods1823 women participated in the Estonian Postmenopausal Hormone Therapy (EPHT) Trial between 1999 and 2004. Women were randomized to open-label continuous combined hormone therapy or no treatment, or to blind hormone therapy or placebo. The average follow-up period was 3.6 years. Prevalence of symptoms and quality of life according to EQ-5D were assessed by annually mailed questionnaires.ResultsIn the hormone therapy arms, less women reported hot flushes (OR 0.20; 95% CI: 0.14–0.28), sweating (OR 0.56; 95% CI: 0.44–0.72), and sleeping problems (OR 0.66; 95% CI: 0.52–0.84), but more women reported episodes of vaginal bleeding (OR 19.65; 95% CI: 12.15–31.79). There was no difference between the trial arms in the prevalence of other symptoms over time. Quality of life did not depend on hormone therapy use.ConclusionPostmenopausal hormone therapy decreased vasomotor symptoms and sleeping problems, but increased episodes of vaginal bleeding, and had no effect on quality of life.Trial registration numberISRCTN35338757

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

Summary 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.

Barriers in cervical cancer screening programs in new European Union member states

qualityscreeningprogramsforcervicalcancercanbeplannedandimplemented. Itis essential to reach high level of information about screening and acceptance of it ‐ both in the population , among medical professions, and decision-makers ‐ and ad herencetostrictquality-assuredprotocols.Alsocontinuousmonitoringandscientif ic evaluation of the activity showing the benefits and potential harms is an integral part of the activity . Within the Health Information framework of the European Commission, the EUROCHIP project performed a number of descriptive studies on cancer indicators in order to identify specific cancer control priorities and problems in various Euro pean countries 5 . The current reports , referring to cervical cancer screening in the Eastern European member states with highest burden of cervical cancer in the EU (i.e. Bulgaria, Estonia, Lithuania, Latvia and Romania ) 6,7 , show unanimously that screening does not yet work well across the EU 8-11 . It emerges that among the gener al public, but also among the professionals as well as decision makers, information on what is screening and on what principles it is based on, is yet not good enough to trigger adequate participation (in the case of the public), adequate collaboration (in thecaseofprofessionals)andnecessarychangesoflegislation(inthecaseofdecision makers).Very low compliance to population-based screening as documented in the reports , included in this issue ofTumori, is one consequence. One important conse quenceofinsufficientawarenessisverylowcompliancetopopulation-basedscreen ing,asdocumentedinthereportsincludedinthisissueofTumori.Itislikely thatthis has also impact on the validity and quality assurance of the screening programs, which are not consistent everywhere.

Impact of implementing a nationwide cervical cancer screening program on female population coverage by Pap-tests in Estonia.

Background The objective of the EUROCHIP project in Estonia was to describe the organized cervical cancer screening program started in 2006 (after pilot studies in 2003–2005), to compare its performance with opportunistic screening, and to define priorities for improvement of the program. Methods Population data was retrieved from Statistics Estonia, data about performed Pap-smear tests within the screening program from the Estonian Cancer Society and from clinics and labs participating in the program, data about Pap-smear tests outside the screening program from the Estonian Health Insurance Fund, and data about cancer incidence and mortality from the Estonian Cancer Registry database. Results During the first year after implementing the nationwide cervical cancer screening program in Estonia, the number of tests outside the organized program remained high. Within the organized program, the number of Pap-tests in different age groups increased with age except for the oldest age group while population coverage with Pap-tests outside the organized screening program decreased with age. The number of cervical cancer cases at early stages increased after implementation of organized screening. The time-frame does not permit to draw any definitive conclusions. Conclusions Implementation of organized cervical cancer screening did not decrease the volume of opportunistic screening. The factors influencing attendance in the organized cervical cancer screening program in different age groups should be studied further. Moreover, a central cancer screening registry without restrictive data protection legislation would improve data collection and enable to evaluate performance of the program on a regular basis.

The effect of hormone therapy on women's quality of life in the first year of the Estonian Postmenopausal Hormone Therapy trial

BackgroundFor postmenopausal women, the main reason to start hormone therapy (HT) is to reduce menopausal symptoms and to improve quality of life (QOL). The aim of this study was to analyse the impact of HT on different aspects of symptom experience and QOL during a randomised trial.A total of 1823 postmenopausal women were recruited into the Estonian Postmenopausal Hormone Therapy (EPHT) trial in 1999–2001. Women were randomised to blind HT, open-label HT, placebo or non-treatment arm. After one year in the trial, a questionnaire was mailed and 1359 women (75%) responded, 686 in the HT arms and 673 in the non-HT arms. Mean age at filling in the questionnaire was 59.8years. The questionnaire included Womens Health Questionnaire (WHQ) to assess menopause specific QOL of middle-aged women together with a 17-item questionnaire on symptoms related to menopause, a question about painful intercourse, and a question about womens self-rated health.ResultsAfter one year in the trial, fewer women in the HT arms reported hot flashes, trouble sleeping, and sweating on the symptom questionnaire. According to WHQ, women in the HT arms had fewer vasomotor symptoms, sleep problems, and problems with sexual behaviour, but more menstrual symptoms; HT had no effect on depression, somatic symptoms, memory, attractiveness, or anxiety. A smaller proportion of women reported painful intercourse in the HT arms. There were no significant differences between the trial arms in women’s self-rated subjective health.ConclusionsThe results from the EPHT trial confirm that HT is not justified for treating symptoms, other than vasomotor symptoms, among postmenopausal women. WHQ proved to be a useful and sensitive tool to assess QOL in this age group of women.

A qualitative study on clinical research in Finland: fragmented governance and volume in the 2000s

Objectives Although concerns over clinical research have been expressed, the governance of clinical research has been little studied. The aim was to describe research policy, volume, funding and concerns over clinical research in Finland. Design A qualitative study and the data were collected from various sources, including documents, statistics and semistructured expert interviews. Setting Finland. Results We found no national policy for clinical research. Many actors were responsible for facilitating, directing, regulating and funding clinical research, but no actor had the main responsibility. Health professionals were the main drivers for clinical research. The role of the health ministry was small. The ministry distributed state money for clinical research in health services (EVO-money), but did not use it to direct research. Municipalities responsible for health services or national health insurance had little interest in clinical research. The Academy of Finland had had initiatives to promote clinical research, but they had not materialised in funding. Clinical research was common and internationally competitive, but its volume had declined relatively in the 2000s. Industry was an important private funder, mainly supporting drug trials made for licensing purposes. Drug trials without an outside sponsor (academic projects) declined between 2002 and 2010. The funding and its targeting and amount were no ones responsibility. Concerns over clinical research were similar as in other countries, but it had appeared late. Conclusions Our results suggest fragmented governance and funding in clinical research. The unsystematic research environment has not prevented clinical research from flourishing, but the public health relevance of the research carried out and its sustainability are unclear.

Results from a blind and a non-blind randomised trial run in parallel: experience from the Estonian Postmenopausal Hormone Therapy (EPHT) Trial

BackgroundThe Estonian Postmenopausal Hormone Therapy (EPHT) Trial assigned 4170 potential participants prior to recruitment to blind or non-blind hormone therapy (HT), with placebo or non-treatment the respective alternatives. Before having to decide on participation, women were told whether they had been randomised to the blind or non-blind trial. Eligible women who were still willing to join the trial were recruited. After recruitment participants in the non-blind trial (N = 1001) received open-label HT or no treatment, participants in the blind trial (N = 777) remained blinded until the end of the trial. The aim of this paper is to analyse the effect of blinding on internal and external validity of trial outcomes.MethodsEffect of blinding was calculated as the hazard ratio of selected chronic diseases, total mortality and all outcomes. For analysing the effect of blinding on external validity, the hazard ratios from women recruited to the placebo arm and to the non-treatment arm were compared with those not recruited; for analysing the effect of blinding on internal validity, the hazard ratios from the blind trial were compared with those from the non-blind trial.ResultsThe women recruited to the placebo arm had less cerebrovascular disease events (HR 0.43; 95% CI: 0.26-0.71) and all outcomes combined (HR 0.76; 95% CI: 0.63-0.91) than those who were not recruited. Among women recruited or not recruited to the non-treatment arm, no differences were observed for any of the outcomes studied.Among women recruited to the trial, the risk for coronary heart disease events (HR 0.77; 95% CI: 0.64-0.93), cerebrovascular disease events (HR 0.66; 95%CI: 0.47-0.92), and all outcomes combined (HR 0.82; 95% CI: 0.72-0.94) was smaller among participants in the blind trial than in the non-blind trial. There was no difference between the blind and the non-blind trial for total cancer (HR 0.95; 95% CI: 0.64-1.42), bone fractures (0.93; 95% CI: 0.74-1.16), and total mortality (HR 1.03; 95% CI: 0.53-1.98).ConclusionsThe results from blind and non-blind trials may differ, even if the target population is the same. Blinding may influence both internal and external validity. The effect of blinding may vary for different outcome events.Trial registration[ISRCTN35338757]