Publications by authors named "Ahti Anttila"

121 Publications

Setting the record straight-Correcting uterine cancer incidence and mortality in the Nordic countries by reallocation of unspecified cases.

Acta Obstet Gynecol Scand 2022 Jan 18. Epub 2022 Jan 18.

Finnish Cancer Registry, Helsinki, Finland.

Introduction: The incidence of and mortality from cancers of the cervix uteri and corpus uteri are underestimated if the presence of uterine cancers, where the exact topography (site of origin) is not specified, is omitted. In this paper we present the corrected figures on mortality from and incidence of cervix and corpus uteri cancers in the Nordic countries by reallocating unspecified uterine cancer deaths and cases to originate either from the corpus uteri or cervix uteri. To further validate the accuracy of reallocation, we also analyzed how well the reallocation captures the changes occurring as the result of a transition in cause of death coding in Norway that took place in 2005.

Material And Methods: This study uses data available in the NORDCAN database, which contains aggregated cancer data from all the Nordic countries for the years 1960-2016. The unspecified uterine cancer cases and deaths were reallocated to either cervix uteri or corpus uteri based on the estimated probability that follows the distribution of cases and deaths with verified topography. The estimated proportions of cases and deaths for both cancers were calculated for each combination of age group, year, and country as a proportion of cases (and deaths, respectively) with known topography. Annual age-standardized rates were calculated by direct age-adjustment.

Results: The proportions of unspecified uterine cancers were higher in the mortality data than in incidence data, with mean values for 1960-2016 ranging between 5.1% and 26.6% and between 0.2% and 6.8% by country, respectively. In the Nordic countries combined, the reallocation increased the number of cases by 4% and deaths by approximately 20% for both cancers. Finland was the only Nordic country where the mortality rate did not increase substantially after reallocation.

Conclusions: The reallocation procedure had a significant impact on mortality from cancers of the cervix and corpus uteri for countries where the proportion of cancer deaths coded as uterus, not otherwise specified, is substantial. More effort to validate cause of death data with incidence data from cancer registries is warranted to avoid erroneous conclusions of temporal trends based on uncorrected cancer burden.
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http://dx.doi.org/10.1111/aogs.14314DOI Listing
January 2022

Contest of Best Practices tackling social inequalities in cancer prevention: an iPAAC initiative.

Eur J Public Health 2021 Dec 15. Epub 2021 Dec 15.

Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, FISABIO, Valencia, Spain.

Current health promotion and early cancer detection programmes yield different results depending on the social group and have a different impact among individuals. Thus, they may generate social inequalities in health. The Contest of Best Practices tackling social inequalities in cancer prevention is an initiative that emerged in the framework of the Innovative Partnership for Action Against Cancer Joint Action. This contest identifies interventions that have proven to be effective in reducing social inequalities in cancer prevention in European countries, with the aim of sharing lessons learned and inspiring solutions, as well as facilitating replication in other health systems and similar social settings.
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http://dx.doi.org/10.1093/eurpub/ckab206DOI Listing
December 2021

Comparability and validity of cancer registry data in the northwest of Russia.

Acta Oncol 2021 Oct 23;60(10):1264-1271. Epub 2021 Aug 23.

Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France.

Background: Despite the elaborate history of statistical reporting in the USSR, Russia established modern population-based cancer registries (PBCR) only in the 1990s. The quality of PBCRs data has not been thoroughly analyzed. This study aims at assessing the comparability and validity of cancer statistics in regions of the Northwestern Federal District (NWFD) of Russia.

Material And Methods: Data from ten Russian regional PBCRs covering ∼13 million (∼5 million in St. Petersburg) were processed in line with IARC/IACR and ENCR recommendations. We extracted and analyzed all registered cases but focused on cases diagnosed between 2008 and 2017. For comparability and validity assessment, we applied established qualitative and quantitative methods.

Results: Data collection in NWFD is in line with international standards. Distributions of diagnosis dates revealed higher variation in several regions, but overall, distributions are relatively uniform. The proportion of multiple primaries between 2008 and 2017 ranged from 6.7% in Vologda Oblast to 12.4% in Saint-Petersburg. We observed substantial regional heterogeneity for most indicators of validity. In 2013-2017, proportions of morphologically verified cases ranged between 61.7 and 89%. Death certificates only (DCO) cases proportion was in the range of 1-14% for all regions, except for Saint-Petersburg (up to 23%). The proportion of cases with a primary site unknown was between 1 and 3%. Certain cancer types (e.g., pancreas, liver, hematological malignancies, and CNS tumors) and cancers in older age groups showed lower validity.

Conclusion: While the overall level of comparability and validity of PBCRs data of four out of ten regions of NWFD of Russia meets the international standards, differences between the regions are substantial. The local instructions for cancer registration need to be updated and implemented. The data validity assessment also reflects pitfalls in the quality of diagnosis of certain cancer types and patient groups.
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http://dx.doi.org/10.1080/0284186X.2021.1967443DOI Listing
October 2021

Cervical testing beyond the screening target age - A register-based cohort study from Finland.

Gynecol Oncol 2021 08 30;162(2):315-321. Epub 2021 May 30.

Mass Screening Registry, Finnish Cancer Registry, Helsinki, Finland.

Objective: It has been proposed that cervical cancer screening should be continued in women with previous abnormal results or irregular attendance. We examined the coverage and factors that might influence cervical testing beyond the age range of the organized cervical screening programme in Finland. The national programme invites women in every five years least until the age of 60. After the stopping age, only opportunistic service is available.

Methods: Data on cervical testing were collected from the Mass Screening Registry and providers of opportunistic Pap/HPV-testing and were linked with information on socio-economic variables. The study included 373,353 women who had at least one invitation to the national screening programme between ages 50-60 years, and who were aged 65-74 years in the follow-up period 2006-2016. Multivariable binomial regression models were conducted to determine associations.

Results: Altogether 33% of the study population had been tested at least once at ages 65-74 years. Previous regular screening attendance (adjRR 1.70; 95% CI 1.67-1.73) and earlier abnormal results (adjRR 2.08; 95% CI 2.04-2.12) were most clearly related to higher testing adherence at older age. Other factors related to higher testing adherence were urban area of residence, domestic mother tongue, high education level, and high socio-economic status.

Conclusion: Testing at older age was frequent with normal results, whereas only a small proportion of women with earlier abnormal results or irregular attendance were tested. The upper age limit of the national programme should be raised to 65 years, and the invitations thereafter should be targeted to selected high-risk groups.
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http://dx.doi.org/10.1016/j.ygyno.2021.05.019DOI Listing
August 2021

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

Prev Med Rep 2021 Jun 30;22:101392. Epub 2021 Apr 30.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

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.
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http://dx.doi.org/10.1016/j.pmedr.2021.101392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122113PMC
June 2021

Sustainability and monitoring of the European Code Against Cancer: Recommendations.

Cancer Epidemiol 2021 06 7;72:101933. Epub 2021 Apr 7.

Environment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), 150 cours Albert Thomas, 69372, Lyon CEDEX 08, France.

Introduction: As part of the third European Commission's Joint Action on Cancer (Innovative Partnership for Action Against Cancer, iPAAC), the International Agency for Research on Cancer (IARC) was commissioned to produce a report on recommendations to sustain and monitor future updates of the European Code Against Cancer (ECAC).

Materials And Methods: A co-creational consultation process, including a virtual workshop, was carried out. More than 100 experts in cancer prevention, public health, communication and representatives of European authorities provided input on the scope of future editions of the ECAC, including updating the scientific evidence and its maintenance, and on strategies for its implementation and dissemination across Europe.

Results And Discussion: Overwhelming support for the need of the ECAC and its continuous updating, optimization and wider dissemination was expressed by all the stakeholders. Eight recommendations and four research needs summarise the assessment and pave the way for the future of the ECAC.
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http://dx.doi.org/10.1016/j.canep.2021.101933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140405PMC
June 2021

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

MDM Policy Pract 2021 Jan-Jun;6(1):2381468320984974. Epub 2021 Jan 29.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

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. 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. 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. 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.
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http://dx.doi.org/10.1177/2381468320984974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863172PMC
January 2021

Comparison of cytology and human papillomavirus-based primary testing in cervical screening programs in the Nordic countries.

J Med Screen 2021 12 9;28(4):464-471. Epub 2021 Feb 9.

Finnish Cancer Registry, Helsinki, Finland.

Objective: To compare primary test positivity in cytology and human papillomavirus-based screening between different Nordic cervical cancer screening programs using harmonized register data.

Methods: This study utilized individual-level data available in national databases in Finland, Iceland, Norway, and Sweden. Cervical test data from each country were converted to standard format and aggregated by calculating the number of test episodes for every test result for each calendar year and one-year age group and test method. Test positivity was estimated as the proportion of positive test results of all primary test episodes with a valid test result for "any positive" and "clearly positive" results.

Results: The age-adjusted rate ratio for any positive test results in primary human papillomavirus-based screening compared to cytology was 1.66 (95% CI 1.64-1.68). The age-adjusted rate ratio for clearly positive test results was 1.02 (95% CI 1.00-1.05). A decreasing rate ratio by age was seen in both any positive and clearly positive test results. Test positivity increased over time in Iceland, Norway, and Sweden but slightly decreased in Finland.

Conclusions: The probability of any positive test result was higher in human papillomavirus testing than in primary cytology, even though the cross-sectional detection of a clearly positive test result was the same. Human papillomavirus testing can still lead to an improved longitudinal sensitivity through a larger number of follow-up tests and the opportunity to identify women with a persistent human papillomavirus infection. Further research on histologically verified precancerous lesions is needed in primary as well as repeat testing.
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http://dx.doi.org/10.1177/0969141321992404DOI Listing
December 2021

Piloting gender-oriented colorectal cancer screening with a faecal immunochemical test: population-based registry study from Finland.

BMJ Open 2021 02 8;11(2):e046667. Epub 2021 Feb 8.

Finnish Cancer Registry, Cancer Society of Finland Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.

Objective: To assess the feasibility and evaluate the performance of a relaunched colorectal cancer (CRC) screening programme with different cut-offs for men and women.

Design: Population-based registry study.

Setting: Nine municipalities in Finland which started CRC screening with faecal immunochemical test (FIT) in April 2019 with cut-off levels 70 µg Hg/g faeces for men and 25 µg Hg/g faeces for women.

Participants: Men (n=13 059) and women (n=14 669) aged 60-66 years invited to screening during the first programme year.

Outcome Measures: Participation rates, positivity rates, detection rates of CRC and advanced adenoma (AA), and positive predictive values (PPV) of FIT for CRC and AA.

Results: Altogether 21 993 invitees returned stool samples. The participation rate of women (83.4%; 95% CI 82.8 to 84.0) was significantly higher than that of men (74.7%; 95% CI 73.9 to 75.4). The positivity rates were 2.4% (2.2 to 2.7) and 2.8% (2.5 to 3.1), respectively. In total, 37 CRCs and 116 AAs were detected. The detection rates of CRC and AA per 1000 participants were 1.8 (1.1 to 2.9) and 7.2 (5.6 to 9.1) for men and 1.6 (0.9 to 2.4) and 3.8 (2.8 to 5.0) for women. The PPVs per 100 positive tests were 6.6 (4.0 to 10.3) and 25.7 (20.6 to 31.4) for men and 6.4 (3.9 to 9.8) and 15.5 (11.6 to 20.2) for women.

Conclusions: The chosen FIT strategy narrowed the gap in the diagnostic performance between men and women especially in the detection of CRC. The participation rates were excellent. The levels of positivity and detection rates were moderate and need further action. The results indicate that gender-specific protocols can be introduced to organised CRC screening. It is yet to be seen whether they are more effective than a uniform screening protocol.
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http://dx.doi.org/10.1136/bmjopen-2020-046667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871693PMC
February 2021

Effectiveness of the cervical cancer prevention programme: a case-control mortality audit in Lithuania.

Eur J Cancer Prev 2020 11;29(6):504-510

Mass Screening Registry/Finnish Cancer Registry, Helsinki, Finland.

The cervical cancer burden in Lithuania has remained high, and there are no previous effectiveness studies of cervical cancer prevention programme in the country. We investigated the effect of a prevention programme on the risk of mortality from cervical cancer in Lithuania by conducting a mortality audit study. The register-based case-control study included 715 cervical cancer deaths that occurred during 2010-2015 in Lithuania and their 2145 matched controls. Screening histories for cases and controls were obtained from the National Health Insurance Fund database. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression and corrected for self-selection bias. Index screening was associated with a 56% reduction in the cervical cancer death risk, OR: 0.44; 95% CI 0.26-0.74. The ORs for stage I and stage II+ cancers were 0.80; 95% CI 0.32-2.00 and 0.36; 95% CI 0.21-0.62, respectively. The preventive effect was statistically significant for women aged ≥40 years, while nonsignificant for younger. In women who died of cervical cancer, 71% were not invited and 88% were not screened within the recommended 36 months prior to index date. Among cases with index invitation, 32% had index screening compared to 70% in controls. In conclusion, participation in screening has been effective in reducing cervical cancer mortality in Lithuania. The study shows poor screening attendance, emphasizing the importance of greater efforts at the national level to improve the effectiveness of the screening.
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http://dx.doi.org/10.1097/CEJ.0000000000000603DOI Listing
November 2020

Differences in cervical test coverage by age, socioeconomic status, ethnic origin and municipality type - A nationwide register-based study.

Prev Med 2020 10 18;139:106219. Epub 2020 Jul 18.

Finnish Cancer Registry, Unioninkatu 22, 00130 Helsinki, Finland.

An invitational organized cervical cancer screening together with widely spread opportunistic testing has coexisted for decades in Finland. The aim of this study was to examine the coverage of cervical tests by age, socioeconomic status, ethnicity and municipality type within and outside the organized screening program. We had a cohort of women of whom 1,2 million were in the target age range of screening and residing in Finland in 2010-2014. Data on Pap and/or HPV -tests within and outside the screening program were collected from the Mass Screening Registry, the pathology laboratories and the health insurance reimbursement registry and five-year population coverages of tests were reported. The total test coverage was 86.0%; 95% CI, (85.8-86.1), and was notably lower for those with an unknown socioeconomic status and pensioners (68.8%; 95% CI, (67.9-69.6) and 77.1%; 95% CI, (76.5-77.6), respectively) compared to upper-level employers (89.8%; 95% CI, (89.5-90.2)). Coverage was also lower for non-native speaking women (72.4%; 95% CI, (71.8-73.0)) compared to native speakers (86.9%; 95% CI, (86.7-87.0)) and for women living in urban municipalities (85.5%; 95% CI, (85.3-85.7)) compared to semi-urban (87.4%; 95% CI, (87.0-87.8)). Although overall coverage was high, tests within and outside the program seemed to concentrate on women with presumably good access to health services. Tests outside the program were especially common among young women who are at a low risk of invasive cervical cancer. Efforts should be made to reduce excessive opportunistic testing and to increase attendance at the program among hard-to-reach populations.
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http://dx.doi.org/10.1016/j.ypmed.2020.106219DOI Listing
October 2020

Performance indicators in breast cancer screening in the European Union: A comparison across countries of screen positivity and detection rates.

Int J Cancer 2020 10 23;147(7):1855-1863. Epub 2020 Mar 23.

'AOU Città della Salute e della Scienza' University Hospital, CPO Piemonte, Turin, Italy.

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.
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http://dx.doi.org/10.1002/ijc.32968DOI Listing
October 2020

Effect of organised cervical cancer screening on cervical cancer mortality in Europe: a systematic review.

Eur J Cancer 2020 03 21;127:207-223. Epub 2020 Jan 21.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Background: Organised cervical cancer (CC) screening programmes are delivered in many different ways across the European Union and its regions. Our aim was to systematically review the impact of these programs on CC mortality.

Methods: Two independent reviewers identified all eligible studies investigating the effect of organised screening on CC mortality in Europe. Six databases including Embase, Medline and Web of Science were searched (March 2018) with predefined inclusion and exclusion criteria. Only original studies with at least five years of follow-up were considered. Validated tools were used to assess the risk of bias of the included studies.

Results: Ten observational studies were included: seven cohort and three case-control studies. No randomised controlled trials were found, and there were no eligible studies from the eastern and southern part of Europe. Among the eligible studies, seven were conducted in the twentieth century; they scored lower on the risk of bias assessment. CC mortality reduction for women attending organised screening vs. non-attenders ranged from 41% to 92% in seven studies. Reductions were similar in Western (45-92%) and Northern (41-87%) Europe and were higher in the three more recent studies (66-92%). For invited vs. non-invited women, this reduction ranged from 17% to 79% in five studies.

Conclusion: Although data were lacking in Southern and Eastern Europe and the effect size varied between countries and studies, this systematic review provides evidence that organised CC screening reduces CC mortality in those parts of Europe where CC screening was implemented and monitored.
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http://dx.doi.org/10.1016/j.ejca.2019.12.013DOI Listing
March 2020

Key issues that need to be considered while revising the current annex of the European Council Recommendation (2003) on cancer screening.

Int J Cancer 2020 07 26;147(1):9-13. Epub 2020 Feb 26.

CPO, University Hospital 'Città Della Salute e Della Scienza', Turin, Italy.

The 2003 European Council recommendation urging the Member States to introduce or scale up breast, cervical and colorectal cancer screening through an organized population-based approach has had a remarkable impact. We argue that the recommendation needs to be updated for at least two sets of reasons. First, some of the current clinical guidelines include new tests or protocols that were not available at the time of the Council document. Some have already been adopted by organized screening programs, such as newly defined age ranges for mammography screening, Human Papillomavirus (HPV)-based cervical cancer screening, fecal immunochemical test (FIT) and sigmoidoscopy for colorectal cancer screening. Second, the outcomes of randomized trials evaluating screening for lung and prostate cancer have been published recently and the balance between harms and benefits needs to be pragmatically assessed. In the European Union, research collaboration and networking to exchange and develop best practices should be regularly supported by the European Commission. Integration between primary and secondary preventive strategies through comprehensive approaches is necessary not only to maximize the reduction in cancer burden but also to control the rising trend of other noncommunicable diseases sharing the same risk factors.
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http://dx.doi.org/10.1002/ijc.32885DOI Listing
July 2020

Impact of colorectal cancer screening on cancer-specific mortality in Europe: A systematic review.

Eur J Cancer 2020 03 10;127:224-235. Epub 2020 Jan 10.

Erasmus MC, University Medical Center Rotterdam, Department of Public Health, Rotterdam, the Netherlands.

Background: Populations differ with respect to their cancer risk and screening preferences, which may influence the performance of colorectal cancer (CRC) screening programs. This review aims to systematically compare the mortality effect of CRC screening across European regions.

Methods: Six databases including Embase, Medline, Web of Science, PubMed publisher, Google Scholar and Cochrane Library were searched for relevant studies published before March 2018. Bibliographic searches were conducted to select studies assessing the effect of various screening tests (guaiac fecal occult blood test [gFOBT]; flexible sigmoidoscopy [FS]; fecal immunochemical test [FIT] and colonoscopy) on CRC mortality in Europe (PROSPERO protocol: CRD42016042433). Abstract reviewing, data extraction and risk of bias assessment were conducted independently by two reviewers.

Results: A total of 18 studies were included; of which, 11 were related to gFOBT, 4 to FS, 2 to FIT and 1 to colonoscopy; 8 were randomised clinical trials, and 10, observational studies, and an approximately equal number of studies represented Northern, Western and Southern European regions. Among individuals invited to screening, CRC mortality reductions varied from 8% to 16% for gFOBT and from 21% to 30% for FS. When studies with a high risk of bias were considered, ranges were more extensive. The estimated effectiveness of gFOBT and FS screening appeared similar across different European regions.

Conclusions: CRC mortality impact of inviting individuals with similar adopted screening strategies (gFOBT or FS) may be consistent across several European settings.
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http://dx.doi.org/10.1016/j.ejca.2019.12.014DOI Listing
March 2020

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

Eur J Cancer 2020 03 10;127:191-206. Epub 2020 Jan 10.

Erasmus MC, University Medical Center Rotterdam, Department of Public Health, Rotterdam, the Netherlands.

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.
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http://dx.doi.org/10.1016/j.ejca.2019.12.010DOI Listing
March 2020

All-cause mortality versus cancer-specific mortality as outcome in cancer screening trials: A review and modeling study.

Cancer Med 2019 10 18;8(13):6127-6138. Epub 2019 Aug 18.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background: All-cause mortality has been suggested as an end-point in cancer screening trials in order to avoid biases in attributing the cause of death. The aim of this study was to investigate which sample size and follow-up is needed to find a significant reduction in all-cause mortality.

Methods: A literature review was conducted to identify previous studies that modeled the effect of screening on all-cause mortality. Microsimulation modeling was used to simulate breast cancer, lung cancer, and colorectal cancer screening trials. Model outputs were: cancer-specific deaths, all-cause deaths, and life-years gained per year of follow-up.

Results: There were large differences between the evaluated cancers. For lung cancer, when 40 000 high-risk people are randomized to each arm, a significant reduction in all-cause mortality could be expected between 11 and 13 years of follow-up. For breast cancer, a significant reduction could be found between 16 and 26 years of follow-up for a sample size of over 300 000 women in each arm. For colorectal cancer, 600 000 persons in each arm were required to be followed for 15-20 years. Our systematic literature review identified seven papers, which showed highly similar results to our estimates.

Conclusion: Cancer screening trials are able to demonstrate a significant reduction in all-cause mortality due to screening, but require very large sample sizes. Depending on the cancer, 40 000-600 000 participants per arm are needed to demonstrate a significant reduction. The reduction in all-cause mortality can only be detected between specific years of follow-up, more limited than the timeframe to detect a reduction in cancer-specific mortality.
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http://dx.doi.org/10.1002/cam4.2476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792501PMC
October 2019

Productivity losses associated with premature mortality due to cancer in Russia: A population-wide study covering 2001-2030.

Scand J Public Health 2019 Jul;47(5):482-491

6 Section of Cancer Surveillance, International Agency for Research on Cancer, France.

Productivity losses related to premature cancer mortality have been assessed for most developed countries but results for Russia are limited to cross-sectional reports. The aim of this study was to quantify productivity costs due to cancer mortality in Russia between 2001 and 2015 and project this to 2030. : Cancer mortality data (2001-2015) were acquired from the State Cancer Registry, whereas population data, labour force participation rates and annual earnings were retrieved from the Federal State Statistics Service. Cancer mortality was projected to 2030 and the human capital approach was applied to estimate productivity losses. : The total annual losses increased from US6.5b in 2001-2005 to US$8.1b in 2011-2015, corresponding to 0.24% of the annual gross domestic product. The value is expected to remain high in 2030 (US$7.5b, 0.14% of gross domestic product). Productivity losses per cancer death are predicted to grow faster in women (from US$18,622 to US$22,386) than in men (from US$25,064 to US$28,459). Total losses were found to be highest for breast cancer in women (US$0.6b, 20% of overall losses in women) and lung cancer in men (US$1.2b, 24%). The absolute predicted change of annual losses between 2011-2015 and 2026-2030 was greatest for cervix uteri (+US$214m) in women and for lip, oral and pharyngeal cancers in men (+US$182m).
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http://dx.doi.org/10.1177/1403494819845565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651608PMC
July 2019

Cancer incidence among workers with blood lead measurements in two countries.

Occup Environ Med 2019 09 11;76(9):603-610. Epub 2019 Jul 11.

International Agency for Research on Cancer, Lyon, France.

Objective: Study carcinogenicity of inorganic lead, classified as 'probably carcinogenic' to humans by the International Agency for Research on Cancer (brain, lung, kidney and stomach).

Methods: We conducted internal and external analyses for cancer incidence in two cohorts of 29 874 lead-exposed workers with past blood lead data (Finland, n=20 752, Great Britain=9122), with 6790 incident cancers. Exposure was maximum measured blood lead.

Results: The combined cohort had a median maximum blood lead of 29 μg/dL, a mean first blood lead test of 1977, and was 87% male. Significant (p<0.05) positive trends, using the log of maximum blood lead, were found for brain cancer (malignant), Hodgkin's lymphoma, lung cancer and rectal cancer, while a significant negative trend was found for melanoma. Borderline significant positive trends (0.05≤p≤0.10) were found for oesophageal cancer, meningioma and combined malignant/benign brain cancer. Categorical analyses reflected these trends. Significant interactions by country were found for lung, brain and oesophageal cancer, with Finland showing strong positive trends, and Great Britain showing modest or no trends. Larynx cancer in Finland also showed a positive trend (p=0.05). External analyses for high exposure workers (maximum blood lead >40 μg/dL) showed a significant excess for lung cancer in both countries combined, and significant excesses in Finland for brain and lung cancer. The Great Britain data were limited by small numbers for some cancers, and limited variation in exposure.

Conclusions: We found strong positive incidence trends with increasing blood lead level, for several outcomes in internal analysis. Two of these, lung and brain cancer, were sites of a priori interest.
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http://dx.doi.org/10.1136/oemed-2019-105786DOI Listing
September 2019

Low-grade screen-detected ductal carcinoma in situ progresses more slowly than high-grade lesions: evidence from an international multi-centre study.

Breast Cancer Res Treat 2019 Oct 28;177(3):761-765. Epub 2019 Jun 28.

Centre for Global Health, National Cancer Institute, Rockville, MD, USA.

Purpose: Nuclear grade is an important indicator of the biological behaviour of ductal carcinoma in situ (DCIS). De-escalation of treatment has been suggested for low-grade DCIS. Our aim is to estimate the relative rate of progression of DCIS by nuclear grade by analysing the distribution of nuclear grade by detection at initial or subsequent screening.

Methods: We asked International Cancer Screening Network sites to complete, based on their screening and clinical databases, an aggregated data file on DCIS detection, diagnosis and treatment.

Results: Eleven screening programs reported 5068 screen-detected pure DCIS in nearly 7 million screening tests in women 50-69 years of age. For all programs combined, low-grade DCIS were 20.1% (range 11.4-31.8%) of graded DCIS, intermediate grade 31.0% and high grade 48.9%. Detection rates decreased more steeply from initial to subsequent screening in low compared to high-grade DCIS: the ratios of subsequent to initial detection rates were 0.39 for low grade, 0.51 for intermediate grade, and 0.75 for high grade (p < 0.001).

Conclusions: These results suggest that the duration of the preclinical detectable phase is longer for low than for high-grade DCIS. The findings from this large multi-centre, international study emphasize that the management of low-grade DCIS should be carefully scrutinized in order to minimize overtreatment of screen-detected slow-growing or indolent lesions. The high variation by site in the proportion of low grade suggests that further pathology standardization and training would be beneficial.
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http://dx.doi.org/10.1007/s10549-019-05333-6DOI Listing
October 2019

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

Acta Oncol 2019 Sep 20;58(9):1199-1204. Epub 2019 May 20.

Finnish Cancer Registry , Helsinki , Finland.

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. 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. 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. 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.
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http://dx.doi.org/10.1080/0284186X.2019.1615637DOI Listing
September 2019

Effectiveness of cervical cancer screening at age 65 - A register-based cohort study.

PLoS One 2019 26;14(3):e0214486. Epub 2019 Mar 26.

Finnish Cancer Registry, Helsinki, Finland.

Most cervical cancer deaths in Finland occur after the termination of the national screening program, targeted at women aged 30 to 64 years. The purpose of this study was to examine the effectiveness of screening at age 65 in reducing cervical cancer mortality. A register-based cohort study was performed with a follow-up period between 1991 and 2014. Mortality risk ratios for incident cervical cancer cases diagnosed at age 65 or older were compared between women invited and not invited for screening. The background risk difference between the studied areas was accounted for by using a reference cohort. The relative risk of death for women invited for cervical cancer screening at the age of 65 was 0.52 (95% CI: 0.29-0.94). The relative risks for women not attending and attending to screening with respect to the uninvited were 1.28 (CI: 0.65-2.50) and 0.28 (CI: 0.13-0.59), respectively. Inviting 65-year-old women for screening has been effective in reducing cervical cancer mortality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214486PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435141PMC
December 2019

Correction: Association of symptoms and interval breast cancers in the mammography-screening programme: population-based matched cohort study.

Br J Cancer 2019 Apr;120(7):773-774

Mass Screening Registry, Finnish Cancer Registry, FI-00130, Helsinki, Finland.

The authors report that the labels indicating the symptom types and no symptom lines in the original version of Figure 2 were missing. The correct version of Figure 2 with the labels included is provided below.
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http://dx.doi.org/10.1038/s41416-019-0417-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461836PMC
April 2019

Performance of colorectal cancer screening in the European Union Member States: data from the second European screening report.

Gut 2019 07 10;68(7):1232-1244. Epub 2018 Dec 10.

SSD Epidemiologia e screening - CPO, University Hospital 'Città della Salute e della Scienza', Turin, Italy.

Objective: To present comparative data about the performance of colorectal cancer (CRC) screening programmes in the European Union Member States (EU MSs).

Design: Cross-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.

Results: Participation 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, p<0.001) with participation in breast cancer screening in the same areas. Screening performance showed a large variability. Compliance with referral for colonoscopy (total colonoscopy (TC)) assessment ranged between 64% and 92%; TC completion rate ranged between 92% and 99%. PR and DR of advanced adenomas and CRC were higher in FIT, as compared with gFOBT programmes, and independent of the protocol among men, older subjects and those performing their first screening.

Conclusions: The 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.
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http://dx.doi.org/10.1136/gutjnl-2018-317293DOI Listing
July 2019

Cancer incidence and mortality patterns in women with breast symptoms in the mammography screening programme: A matched cohort analysis.

Int J Cancer 2019 06 11;144(12):2928-2935. Epub 2019 Jan 11.

Mass Screening Registry, Finnish Cancer Registry, Helsinki, Finland.

Efforts to reduce mortality through early detection and diagnosis has intensified in the recent decade. An important risk factor, 'breast symptoms' reported by women during screening visit, remains overlooked. In this population based matched cohort study using Finnish National Breast Cancer Screening Program (FNBCSP), we assessed the association between breast symptoms reported at screening visit and the risk of cancer incidence and breast cancer mortality and all-cause mortality followed-up over a period of 24 years. For each visit with symptoms, non-symptomatic controls were matched (1:1 for lump and retraction; 1:2 for nipple discharge) based on age at screening visit, year of invitation, number of invited visits, and municipality of invitation. Women who reported lump or retraction had about two-fold risk of breast cancer incidence, three-fold risk of breast cancer mortality and all-cause mortality respectively as compared to women without respective symptoms (p-value<0.05). We found a substantial difference (p-value<0.05) in mortality rates throughout the follow-up period between symptomatic and asymptomatic group. In absolute terms, after the follow-up period for women who reported lump, 180 died from breast cancer as compared to 70 deaths in those without lump, per 10,000 person-years of follow-up, and 315 versus 160 all-cause deaths per 10,000 person-years in women with and without lump respectively. our study provides comprehensive evidence that women with breast symptoms remain in a higher risk of dying over a very long period. The findings indicate needs to develop improvements in the guidelines for screening and clinical services for women presenting with symptoms.
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http://dx.doi.org/10.1002/ijc.32035DOI Listing
June 2019

Association of symptoms and interval breast cancers in the mammography-screening programme: population-based matched cohort study.

Br J Cancer 2018 11 7;119(11):1428-1435. Epub 2018 Nov 7.

Mass Screening Registry, Finnish Cancer Registry, FI-00130, Helsinki, Finland.

Background: We assessed the association between symptoms reported at breast cancer screening visits and interval cancers (ICs) in a prospective manner.

Methods: This population-based matched cohort study uses data of the Finnish National Breast Cancer Screening Programme that invites women aged 50-69 years old during 1992-2012. Subjects who attended screening with symptoms were matched with asymptomatic reference cohorts based on age at screening visit, year of invitation, number of invited visits and municipality of invitation. The primary outcome was ICs.

Results: Women with a lump had a threefold (hazard ratio 3.7, 95% confidence interval (CI) 3.0-4.6) risk of ICs and a higher risk (hazard ratio 1.7, 95% CI 1.4 to 2.0) at the subsequent visit compared with those without a lump. The fatal interval cancer risk increased by 0.39 per 1000 screens with a lump. The cumulative incidences of interval cancer increased within a month of a mammography-negative visit with a lump and after about 6 months of the visit with retraction or nipple discharge.

Conclusion: Women with breast symptoms have a clearly increased risk of interval breast cancer after the screening visit. Our findings indicate the need for different screening strategies in symptomatic women.
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http://dx.doi.org/10.1038/s41416-018-0308-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265247PMC
November 2018

The legal framework for European cervical cancer screening programmes.

Eur J Public Health 2019 04;29(2):345-350

Finnish Cancer Registry, Helsinki, Finland.

Background: A comprehensive legal framework needs to be developed to run the health services and to regulate the information systems required to manage and to ensure the quality of cancer screening programmes. The aim of our study was to document and to compare the status of legal basis for cervical screening registration in European countries.

Methods: An electronic questionnaire including questions on governance, decision-making structures and legal framework was developed. The primary responses were collected by September 2016.

Results: We sent the questionnaire to representatives of 35 European countries (28 countries of the EU, with the United Kingdom included as 4 countries; 4 EFTA member countries: Iceland, Liechtenstein, Norway, and Switzerland); responses were collected from 33 countries. The legal framework makes it possible to personally invite individuals in 29 countries (88%). Systematic screening registration in an electronic registry is legally enshrined in 23 countries (70%). Individual linkage of records between screening and cancer registries is allowed in 19 of those countries. Linkage studies involving cancer and screening registries have been conducted in 15 countries.

Conclusion: Although the majority of EU/EFTA countries have implemented population-based screening, only half of them have successfully performed record linkage studies, which are nevertheless a key recommendation for quality assurance of the entire screening process. The European legislation is open to the possibility of using health data for these purposes; however, member states themselves must recognize the public interest to create a legal basis, which would enable all the necessary functions for high-quality cancer screening programmes.
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http://dx.doi.org/10.1093/eurpub/cky200DOI Listing
April 2019
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