Divergent effects of switching from cytology to HPV-based screening in the Nordic countries.

BACKGROUND: Cervical cytology has been the primary method of cervical cancer screening for decades. Tests that detect viral HPV are shown in several randomized trials to provide better protection against cancer compared with cytology. HPV-based screening has been implemented alongside cytology in the Nordic countries for several years. The aim of this study was to compare cytology and HPV-based screening in the colposcopy referrals and detection rates of cervical lesions. METHODS: Individual-level screening data from Finland, Iceland, Norway and Sweden were harmonized and aggregated locally. We utilized data for tests taken during years 2015-17 and biopsies taken during years 2015-19 to allow 24 months of follow-up. Age-standardized estimates and age-adjusted risk ratios for six different outcomes of screening management were calculated. RESULTS: The age-standardized colposcopy rates were higher in HPV-based testing compared with cytology in Finland (3.5% vs. 0.9%) and Norway (6.0% vs. 4.1%) but lower in Sweden (3.7% vs. 4.9%). The relative detection rate of cervical intraepithelial neoplasia grade 2 and above in HPV-based testing compared with cytology was highest in Finland (RR 2.37, 95% CI 2.13-2.63) and Norway (RR 1.66, 95% CI 1.57-1.72) while in Sweden the difference was not statistically significant (RR 0.98, 95% CI 0.95-1.00). CONCLUSIONS: The effects of implementing HPV screening varied by country as different screening algorithms were implemented. HPV-based screening increases colposcopy rates mainly through referrals from increased repeat testing and detection rate is therefore significantly higher compared with cytology. Monitoring of these indicators in subsequent rounds of HPV-based screening remains essential.

Similar effectiveness with primary HPV and cytology screening - Long-term follow-up of randomized cervical cancer screening trial.

BACKGROUND: Long-term effects of primary human papillomavirus (HPV) screening on cervical cancer incidence and mortality are still missing. We conducted a long-term follow-up of the Finnish randomized HPV screening trial, the first HPV screening trial run within the routine screening program, to assess these measures. METHODS: During 2003-2008, over 236,000 individuals were randomized (1:1) to HPV and cytology screening arms in Southern Finland. To compare the study arms, we calculated the cervical cancer incidence and mortality rate ratios using Poisson regression. RESULTS: During a total of 3.5 million person-years of follow-up, we observed 129 cervical cancers and 32 cervical cancer deaths in the cytology arm, 139 cervical cancers and 32 cervical cancer deaths in the HPV arm. Compared to the cytology arm, in the HPV arm, the incidence rate ratio was 1.08 (95% CI 0.85-1.37), and the mortality rate ratio was 1.01 (95% CI 0.61-1.64). CONCLUSIONS: We studied the effects of HPV screening on both cervical cancer incidence and mortality for the first time in a setting with an already well-established, high-quality cytology screening program. In this kind of setting with a low incidence of cervical cancer, HPV and cytology screening showed similar effectiveness. HPV screening provides, however, an objective, validated test system and enables self-sampling which can improve screening coverage. More attention is needed yet to ensure the balance between the harms and benefits of HPV screening.

Effectiveness of Cervical Testing in and outside a Screening Program-A Case-Control Study.

In many countries with organized cervical cancer screening, opportunistic Pap and human papillomavirus (HPV) tests are common. However, little is known about their effectiveness. We examined the effect of testing in and outside the Finnish screening program on the risk of cervical cancer. We conducted a case-control study that involved 1677 cases with invasive cervical cancer that were diagnosed between 2010 and 2019. Five- and three-year test intervals were analyzed across all ages, by age group and by cancer morphology subtype. Conditional logistic regression was used, adjusting for socioeconomic variables. Women undergoing any kind of cervical test had a significantly lowered risk of cervical cancer (adjusted OR = 0.43, 95% CI = 0.38-0.48, tests in five-year intervals). The results were similar, regardless of whether the test had been taken in the screening program or outside of it, or whether the interval was five years or three years. Testing of women at ages 35-64 showed the strongest effects, but moderate preventive effects were seen until age 79. No significant effect was seen below age 30. Tests in and outside the program were effective at the screening target age. However, participation in the program should be encouraged for optimal cost-effectiveness. Preventive effects were also seen above the program target ages.

Alternative cytology triage strategies for primary HPV screening.

OBJECTIVE: Primary HPV screening programmes for cervical cancer have been implemented in many European countries using a cytology triage. Nonetheless, the optimal cytology triage strategy for minimizing the harms and maximizing the benefits is yet unclear. We identified key characteristics of different algorithms for HPV screening with cytology triage. METHODS: Using the Finnish randomized HPV screening trial data, we formulated five post-hoc algorithms for HPV screening with a cytology triage, one for HPV screening without a triage and one for cytology screening. Sensitivity, specificity, positive predictive value, colposcopy referral rate and cumulative sensitivity for CIN II + s detected during the first and second screening rounds of the trial were calculated for all algorithms. RESULTS: In the first screening round, direct referral of HPV positives to colposcopy led to the highest sensitivity (94%) accompanied by the lowest specificity (93%). Following HPV positives up with one repeat screen showed 86% sensitivity and 97% specificity. The corresponding figures with two repeat screens were 84% and 98%. In HPV algorithms, where cytology negative HPV positive individuals had no follow-up, the sensitivities were 65-82% and the specificities 98-99%. The Cytology algorithm had a low sensitivity (69%) with a high specificity (99%). Compared to the first round, the second-round sensitivities were lower and specificities similar or higher. CONCLUSIONS: The best balance between sensitivity and specificity was achieved by an HPV algorithm with two repeated follow-up tests. However, all HPV algorithms with cytology triage increased colposcopy volume more than the cytology algorithm and thus provoked overdiagnosis.

Lung cancer incidence among workers biologically monitored for occupational exposure to lead: a cohort study.

OBJECTIVE: Earlier studies have reported increased risks of lung, kidney and brain cancers for exposure to lead. The International Agency for Research on Cancer (IARC) Working Group evaluated inorganic lead and its compounds probably carcinogenic to humans. This study aimed to assess the association between blood lead level in occupational exposure and risk of lung cancer. METHODS: The study was based on the follow-up of lung cancer incidence during 1973-2014 among 20 729 employees biologically monitored for their occupational lead exposure in 1973-1983. Duration of employment in the monitored work was assessed using records from the Finnish Centre for Pensions; and potential confounding by other occupational carcinogens using longitudinal information on the occupation in censuses and the Finnish National Job-Exposure Matrix (FINJEM). Occupation- and gender-specific prevalence of regular tobacco smoking and the socioeconomic status were also utilized in the adjustments for potential confounding. RESULTS: Positive trends were found for the elevated blood lead levels on the lung cancer risk. Among employees with the duration of employment of ≥60 months, the relative risk (RR) of lung cancer was 1.72 [95% confidence interval (CI) 1.28-2.31] for mean blood lead 1.0-1.9 µmol/L and RR 2.63 (95% CI 1.71-4.05) for mean blood lead ≥2.0 µmol/L, compared with mean lead <0.5 µmol/L. The studied potential confounders did not explain the findings on the increased risk for lead exposure. CONCLUSIONS: The current study lends support to the findings that exposure to lead increases lung cancer risk. Increased risks were seen already at rather low blood lead levels.

Optimizing screening with faecal immunochemical test for both sexes - Cost-effectiveness analysis from Finland.

A faecal immunochemical test (FIT) screening pilot was introduced in Finland in 2019 with sex-specific screening strategies. This study aims to model cost-effectiveness of sex-specific strategies for the whole population, and to assess whether the current strategies are optimal. We developed separate MISCAN-Colon models, including different FIT performances, for the Finnish men and women using the first-year data of the FIT screening pilot. We evaluated 180 FIT strategies varying in FIT cut-off, screening interval, age to start, and age to stop screening, and compared them to no-screening by sex. We used incremental cost-effectiveness ratios (ICERs) to identify the optimal strategy after combining all male and female strategies and restricting the analysis by costs and referral rate to diagnostic colonoscopies. Offering annual FIT screening with a cut-off of 25 µg/g at 50-79 years in men and with a cut-off of 10 µg/g at 55-69 years in women was optimal. This combined strategy prevented 28% of colorectal cancer (CRC) cases and 55% of CRC deaths with acceptable costs (ICER = 9000€/life-years gained). Screening at the current target age of 60-74 years was suboptimal for both sexes. Among strategies with the same target age and interval for both sexes, expected benefits from optimal screening were lower but still reasonable. Our results support a wider age range of screening in men, and a lower cut-off for a positive test in women when restrictions on colonoscopy capacity and costs are in place. National FIT screening program should start at younger age.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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.

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

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

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.

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

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.

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

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.

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

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.