Rapid elimination of cervical cancer while maintaining the harms and benefits ratio of cervical cancer screening: a modelling study.

BACKGROUND: Human papillomavirus (HPV) vaccination and intensifying screening expedite cervical cancer (CC) elimination, yet also deteriorate the balance between harms and benefits of screening. We aimed to find screening strategies that eliminate CC rapidly but maintain an acceptable harms-benefits ratio of screening. METHODS: Two microsimulation models (STDSIM and MISCAN) were applied to simulate HPV transmission and CC screening for the Dutch female population between 2022 and 2100. We estimated the CC elimination year and harms-benefits ratios of screening for 228 unique scenarios varying in vaccination (coverage and vaccine type) and screening (coverage and number of lifetime invitations in vaccinated cohorts). The acceptable harms-benefits ratio was defined as the number of women needed to refer (NNR) to prevent one CC death under the current programme for unvaccinated cohorts (82.17). RESULTS: Under current vaccination conditions (bivalent vaccine, 55% coverage in girls, 27.5% coverage in boys), maintaining current screening conditions is projected to eliminate CC by 2042, but increases the present NNR with 41%. Reducing the number of lifetime screens from presently five to three and increasing screening coverage (61% to 70%) would prevent an increase in harms and only delay elimination by 1 year. Scaling vaccination coverage to 90% in boys and girls with the nonavalent vaccine is estimated to eliminate CC by 2040 under current screening conditions, but exceeds the acceptable NNR with 23%. Here, changing from five to two lifetime screens would keep the NNR acceptable without delaying CC elimination. CONCLUSIONS: De-intensifying CC screening in vaccinated cohorts leads to little or no delay in CC elimination while it substantially reduces the harms of screening. Therefore, de-intensifying CC screening in vaccinated cohorts should be considered to ensure acceptable harms-benefits ratios on the road to CC elimination.

Shift in harms and benefits of cervical cancer screening in the era of HPV screening and vaccination: a modelling study.

OBJECTIVE: To calculate the changes in harms and benefits of cervical cancer screening over the first three screening rounds of the Dutch high-risk human papillomavirus (hrHPV) screening programme. DESIGN: Microsimulation study. SETTING: Dutch hrHPV screening programme; women are invited for screening every 5 or 10 years (depending on age and screening history) from age 30 to 65. POPULATION: Partly vaccinated population of 100 million Dutch women. METHODS: Microsimulation model MISCAN was used to estimate screening effects. Sensitivity analyses were performed on test characteristics and attendance. MAIN OUTCOME MEASURES: Harms (screening tests, unnecessary referrals, treatment-related health problems), benefits (CIN2+ diagnoses) and programme efficiency (number needed to screen [NNS]) over the first (period 2017-2021), second (period 2022-2026) and third (period 2027-2031) rounds of hrHPV-based screening. RESULTS: The number of screening tests and CIN2+ diagnoses decreased from the first to the second round (-25.8% and -23.6%, respectively). In the third screening round, these numbers decreased further, albeit only slightly (-2.7% and -5.3%, respectively). NNS to detect a CIN2+ remained constant over the rounds; however, it increased in younger age groups while decreasing in older age groups. CONCLUSION: Both harms and benefits of hrHPV screening decreased over the first screening rounds. For younger women, the efficiency would decrease, whereas longer screening intervals would lead to increased efficiency in older women. Programme efficiency overall remained stable, showing the importance of longer intervals for low-risk women. TWEETABLE ABSTRACT: Cervical cancer screening: both harms and benefits of hrHPV screening will decrease in the future.

Effects of cancer screening restart strategies after COVID-19 disruption.

BACKGROUND: Many breast, cervical, and colorectal cancer screening programmes were disrupted due to the COVID-19 pandemic. This study aimed to estimate the effects of five restart strategies after the disruption on required screening capacity and cancer burden. METHODS: Microsimulation models simulated five restart strategies for breast, cervical, and colorectal cancer screening. The models estimated required screening capacity, cancer incidence, and cancer-specific mortality after a disruption of 6 months. The restart strategies varied in whether screens were caught up or not and, if so, immediately or delayed, and whether the upper age limit was increased. RESULTS: The disruption in screening programmes without catch-up of missed screens led to an increase of 2.0, 0.3, and 2.5 cancer deaths per 100 000 individuals in 10 years in breast, cervical, and colorectal cancer, respectively. Immediately catching-up missed screens minimised the impact of the disruption but required a surge in screening capacity. Delaying screening, but still offering all screening rounds gave the best balance between required capacity, incidence, and mortality. CONCLUSIONS: Strategies with the smallest loss in health effects were also the most burdensome for the screening organisations. Which strategy is preferred depends on the organisation and available capacity in a country.

Reducing unnecessary referrals for colposcopy in hrHPV-positive women within the Dutch cervical cancer screening programme: A modelling study.

BACKGROUND: With the implementation of primary high-risk human papillomavirus (hrHPV) screening in the Netherlands, an increase was observed in the number of unnecessary referrals (≤Cervical Intraepithelial Neoplasia (CIN) 1) to colposcopy. We aimed to investigate which alternative triage strategies safely reduce unnecessary referrals in HPV-based cervical cancer screening programmes. METHODS: Microsimulation model MISCAN was used to simulate an unvaccinated cohort of ten million 30-year old Dutch women. We calculated unnecessary referrals, cervical cancer incidence, mortality, costs and QALYs for 24 triage strategies. Condition for direct referral (atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), conditional on HPV-genotype 16/18/other high risk (OHR)), type of triage test (cytology alone or combined with hrHPV) and time to triage test (6 or 12 months) was varied. RESULTS: The 24 triage strategies had varying effects on the number of unnecessary referrals ranging from -72% to +35%. Adjusting conditions for referral to 'HPV16/18+ and ASC-US+' and 'HPVOHR+ and HSIL+' and extending the interval between tests to 12 months resulted in a reduction in unnecessary referrals of 40% (incidence +0%, mortality -1%). Reduction in unnecessary referrals without genotyping was achieved by adjusting conditions for direct referral to LSIL (12 months to repeat test) (unnecessary referrals -37%, incidence +2%, mortality +0%). CONCLUSIONS: To reduce the number of unnecessary referrals without increasing incidence and mortality by more than 2% in the Dutch cervical cancer screening programme, genotyping for HPV16 or HPV16/18 should be implemented with 12 months to repeat testing.

The optimal HPV-screening protocol in Eastern-Europe: The example of Slovenia.

OBJECTIVE: Eastern European countries are contemplating to introduce the high-risk Human Papillomavirus (HPV)-test as the primary screening test for their cervical cancer screening programme, but its optimal protocol is yet unknown. The aim of this study was to compare the costs, effects and cost-effectiveness of different primary HPV-screening protocols in Eastern Europe, using Slovenia as an example and with respect of local preferences for screening. METHODS: We evaluated 968 HPV-screening protocols, which varied by screening ages, triage tests (i.e. cytology, repeat HPV and/or genotyping) and strategy for women under 35 years old, using the microsimulation model MISCAN-Cervix. RESULTS: Within the subset of strategies that would be acceptable for Slovenian women, the optimal HPV-screening protocol is to start with two cytology tests at age 25 and 28 and switch to 5-yearly HPV screening from age 30 to 65. When also other protocols were considered, the optimal screening strategy would be 5-yearly HPV screening from age 30 to 65 only, improving the cost-effectiveness with 5%. Adding genotyping in the triage algorithm consistently improved cost-effectiveness. Sensitivity analyses showed the robustness of the results for other situations in Eastern Europe. CONCLUSIONS: Despite differences in cervical cancer epidemiology between Eastern and Western European regions where HPV screening was evaluated, the optimal screening protocol was found to be very similar. Furthermore, strategies that were considered socially acceptable to the population were found to be almost as cost-effective as less acceptable strategies and can therefore be considered a viable alternative to prevent opportunistic screening.

Impact of disruptions and recovery for established cervical screening programs across a range of high-income country program designs, using COVID-19 as an example: A modelled analysis.

COVID-19 has disrupted cervical screening in several countries, due to a range of policy-, health-service and participant-related factors. Using three well-established models of cervical cancer natural history adapted to simulate screening across four countries, we compared the impact of a range of standardised screening disruption scenarios in four countries that vary in their cervical cancer prevention programs. All scenarios assumed a 6- or 12-month disruption followed by a rapid catch-up of missed screens. Cervical screening disruptions could increase cervical cancer cases by up to 5-6%. In all settings, more than 60% of the excess cancer burden due to disruptions are likely to have occurred in women aged less than 50 years in 2020, including settings where women in their 30s have previously been offered HPV vaccination. Approximately 15-30% of cancers predicted to result from disruptions could be prevented by maintaining colposcopy and precancer treatment services during any disruption period. Disruptions to primary screening had greater adverse effects in situations where women due to attend for screening in 2020 had cytology (vs. HPV) as their previous primary test. Rapid catch-up would dramatically increase demand for HPV tests in 2021, which it may not be feasible to meet because of competing demands on the testing machines and reagents due to COVID tests. These findings can inform future prioritisation strategies for catch-up that balance potential constraints on resourcing with clinical need.

Management and treatment of cervical intraepithelial neoplasia in the Netherlands after referral for colposcopy.

INTRODUCTION: The aim of this study was to describe trends in the diagnosis and treatment of women referred from the national screening program with cervical intraepithelial neoplasia (CIN) in the Netherlands, and to compare these trends with national guidelines and identify potential areas for improvement for the new primary high-risk HPV screening program. MATERIAL AND METHODS: We conducted a population-based cohort study using data from the Dutch pathology archive. Women aged 29-63 years who took part in the Dutch cervical screening program between 1 January 2005 and 31 December 2014 were selected. Three referral groups were identified: direct referrals and those referred after either one (first indirect referrals) or two (second indirect referrals) repeat cytology tests, totaling 85 239 referrals for colposcopy. The most invasive management technique and the most severe diagnosis of each screening episode was identified. Rates of management techniques were calculated separately by referral type, highest CIN diagnosis and age group. RESULTS: In all, 85.1% of CIN 3 lesions were treated with excision (either large excision or hysterectomy) and 26.4% of CIN 1 lesions were treated with large excision. Rates of overtreatment (CIN 1 or less) in see-and-treat management were higher for indirect referrals than for direct referrals and increased with age. Large excision rates increased with CIN diagnosis severity. CONCLUSIONS: Despite guideline recommendations not to treat, CIN 1 lesions were treated in just over 25% of cases and approximately 15% of CIN 3 lesions were possibly undertreated. Given the expected increase in CIN detection in the new primary high-risk HPV screening program, reduction in CIN 1 treatment and CIN 2 treatment in younger women is needed to avoid an increase in potential harm.

A model-based analysis of the health impacts of COVID-19 disruptions to primary cervical screening by time since last screen for current and future disruptions.

We evaluated how temporary disruptions to primary cervical cancer (CC) screening services may differentially impact women due to heterogeneity in their screening history and test modality. We used three CC models to project the short- and long-term health impacts assuming an underlying primary screening frequency (i.e., 1, 3, 5, or 10 yearly) under three alternative COVID-19-related screening disruption scenarios (i.e., 1-, 2-, or 5-year delay) versus no delay in the context of both cytology-based and human papillomavirus (HPV)-based screening. Models projected a relative increase in symptomatically detected cancer cases during a 1-year delay period that was 38% higher (Policy1-Cervix), 80% higher (Harvard), and 170% higher (MISCAN-Cervix) for underscreened women whose last cytology screen was 5 years prior to the disruption period compared with guidelines-compliant women (i.e., last screen 3 years prior to disruption). Over a woman's lifetime, temporary COVID-19-related delays had less impact on lifetime risk of developing CC than screening frequency and test modality; however, CC risks increased disproportionately the longer time had elapsed since a woman's last screen at the time of the disruption. Excess risks for a given delay period were generally lower for HPV-based screeners than for cytology-based screeners. Our independent models predicted that the main drivers of CC risk were screening frequency and screening modality, and the overall impact of disruptions from the pandemic on CC outcomes may be small. However, screening disruptions disproportionately affect underscreened women, underpinning the importance of reaching such women as a critical area of focus, regardless of temporary disruptions.

Health impacts of COVID-19 disruptions to primary cervical screening by time since last screen: A model-based analysis for current and future disruptions.

Background: We evaluated how temporary disruptions to primary cervical cancer (CC) screening services may differentially impact women due to heterogeneity in their screening history and test modality. Methods: We used three CC models to project the short- and long-term health impacts assuming an underlying primary screening frequency (i.e., 1, 3, 5, or 10 yearly) under three alternative COVID-19-related screening disruption scenarios (i.e., 1-, 2- or 5-year delay) versus no delay, in the context of both cytology-based and HPV-based screening. Results: Models projected a relative increase in symptomatically-detected cancer cases during a 1-year delay period that was 38% higher (Policy1-Cervix), 80% higher (Harvard) and 170% higher (MISCAN-Cervix) for under-screened women whose last cytology screen was 5 years prior to the disruption period compared with guidelines-compliant women (i.e., last screen three years prior to disruption). Over a woman's lifetime, temporary COVID-19-related delays had less impact on lifetime risk of developing CC than screening frequency and test modality; however, CC risks increased disproportionately the longer time had elapsed since a woman's last screen at the time of the disruption. Excess risks for a given delay period were generally lower for HPV-based screeners than for cytology-based screeners. Conclusions: Our independent models predicted that the main drivers of CC risk were screening frequency and screening modality, and the overall impact of disruptions from the pandemic on CC outcomes may be small. However, screening disruptions disproportionately affect under-screened women, underpinning the importance of reaching such women as a critical area of focus, regardless of temporary disruptions. Funding: This study was supported by funding from the National Cancer Institute (U01CA199334). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Megan A Smith receives salary support from the National Health and Medical Research Council, Australia (APP1159491) and Cancer Institute NSW (ECF181561). Matejka Rebolj is funded by Cancer Research UK (reference: C8162/A27047). James O'Mahony is funded by Ireland's Health Research Board (EIA2017054). Karen Canfell receives salary support from the National Health and Medical Research Council, Australia (APP1194679). Emily A. Burger receives salary support from the Norwegian Cancer Society.

Modeling Strategies to Optimize Cancer Screening in USPSTF Guideline-Noncompliant Women.

Importance: In 2018, only half of US women obtained all evidence-based cancer screenings. This proportion may have declined during the COVID-19 pandemic because of social distancing, high-risk factors, and fear. Objective: To evaluate optimal screening strategies in women who obtain some, but not all, US Preventive Services Task Force (USPSTF)-recommended cancer screenings. Design, Setting, and Participants: This modeling study was conducted from January 31, 2017, to July 20, 2020, and used 4 validated mathematical models from the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network using data from 20 million simulated women born in 1965 in the US. Interventions: Forty-five screening strategies were modeled that combined breast, cervical, colorectal, and/or lung cancer (LC) screenings; restricted to 1, 2, 3 or 4 screenings per year; or all eligible screenings once every 5 years. Main Outcomes and Measures: Modeled life-years gained from restricted cancer screenings as a fraction of those attainable from full compliance with USPSTF recommendations (maximum benefits). Results were stratified by LC screening eligibility (LC-eligible/ineligible). We repeated the analysis with 2018 adherence rates, evaluating the increase in adherence required for restricted screenings to have the same population benefit as USPSTF recommendations. Results: This modeling study of 20 million simulated US women found that it was possible to reduce screening intensity to 1 carefully chosen test per year in women who were ineligible for LC screening and 2 tests per year in eligible women while maintaining 94% or more of the maximum benefits. Highly ranked strategies screened for various cancers, but less often than recommended by the USPSTF. For example, among LC-ineligible women who obtained just 1 screening per year, the optimal strategy frequently delayed breast and cervical cancer screenings by 1 year and skipped 3 mammograms entirely. Among LC-eligible women, LC screening was essential; strategies omitting it provided 25% or less of the maximum benefits. The top-ranked strategy restricted to 2 screenings per year was annual LC screening and alternating fecal immunochemical test with mammography (skipping mammograms when due for cervical cancer screening, 97% of maximum benefits). If adherence in a population of LC-eligible women obtaining 2 screenings per year were to increase by 1% to 2% (depending on the screening test), this model suggests that it would achieve the same benefit as USPSTF recommendations at 2018 adherence rates. Conclusions and Relevance: This modeling study of 45 cancer screening strategies suggests that women who are noncompliant with cancer screening guidelines may be able to reduce USPSTF-recommended screening intensity with minimal reduction in overall benefits.

Risk of Gynecologic Cancer after Atypical Glandular Cells Found on Cervical Cytology: A Population-Based Cohort Study.

BACKGROUND: Atypical glandular cells (AGC) are rare abnormalities found on cervical cytology associated with a range of lesions of the female reproductive system. We compared the risk of cervical and other gynecologic cancers following AGC on cervical cytology with the risk following squamous cell abnormalities of comparable severity. METHODS: We used data from the Dutch Pathology Archive (PALGA) from 2000 to 2015 to categorize cervical cytology tests into groups based on most severe cytologic abnormality and correlated follow-up advice (normal cytology and "no follow-up" advice, squamous-cell-based, AGC-based, and combined AGC/squamous-cell based each with either repeat testing or referral advice). Cancer data were linked from the Netherlands Cancer Registry. Cox proportional hazard models were calculated stratified by age [younger (<50 years) and older (50+ years)], adjusted for number of previous primary cytology tests. RESULTS: 8,537,385 cytology smears and 9,061 cancers were included. When repeat cytology testing was advised, HRs of cervical cancer (younger women: HR, 6.91; 95% CI, 5.48-8.71; older women: HR, 3.98; 95% CI, 2.38-6.66) or other gynecologic cancer diagnosis in younger women (HR, 2.82; 95% CI, 1.39-5.74) were significantly higher after an AGC-based abnormality compared with squamous-based abnormalities. Hazards were also significantly higher for "referral" advice cytology, except for cervical cancer among older women (HR, 0.88; 95% CI, 0.63-1.21). CONCLUSIONS: AGC indicates an increased risk of gynecologic cancer compared with squamous-based abnormalities of comparable severity. IMPACT: Gynecologists should be alert for cervical and endometrial cancers when examining women referred following AGC.

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

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

The 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.

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

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.

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

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

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

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.