Lower incidence of vaginal cancer after cervical human papillomavirus screening - long-term follow-up of Finnish randomized screening trial.

OBJECTIVE: Around 70% of vaginal cancers and 40-50% of vulvar cancers are attributable to human papillomavirus (HPV). Globally the burden of these diseases is estimated to grow due to the increasing HPV prevalence and rapidly aging global population. We aimed to examine if HPV screening for cervical cancer has an additional beneficial effect in preventing vaginal and vulvar cancers. To assess this, we used long-term follow-up data from the Finnish randomized HPV screening trial. METHODS: Between 2003 and 2008, over 236,000 women were individually randomized (1:1) to primary HPV or cytology screening in Southern Finland. We followed this cohort up to the year 2020. To compare the study arms, we calculated site-specific and pooled incidence rate ratios (IRRs) and mortality rate ratios (MRRs) for vaginal and vulvar cancers using Poisson regression. RESULTS: During 3,5 million person-years of follow-up, the IRR for vaginal cancer in the HPV arm compared to the cytology arm was 0.40 (95% CI 0.17-0.88) and the corresponding MRR was 0.74 (95% 0.21-2.24). The corresponding IRR for vulvar cancer was 0.73 (95% 0.50-1.08) and the MRR was 0.64 (95% 0.23-1.62). The pooled IRR was 0.67 (95% 0.47 ̶ 0.95) and MRR 0.67 (95% 0.31 ̶ 1.37). CONCLUSION: We found lower incidence of vaginal cancers with HPV screening compared to cytology screening. To validate our results, we recommend analyzing data on vaginal and vulvar cancers also from other HPV screening studies.

Regression calibration of self-reported mobile phone use to optimize quantitative risk estimation in the COSMOS study.

The Cohort Study of Mobile Phone Use and Health (COSMOS) has repeatedly collected self-reported and operator-recorded data on mobile phone use. Assessing health effects using self-reported information is prone to measurement error, but operator data were available prospectively for only part of the study population and did not cover past mobile phone use. To optimize the available data and reduce bias, we evaluated different statistical approaches for constructing mobile phone exposure histories within COSMOS. We evaluated and compared the performance of four regression calibration (RC) methods (simple, direct, inverse, and generalized additive model for location, shape, and scale), complete-case (CC) analysis and multiple imputation (MI) in a simulation study with a binary health outcome. We used self-reported and operator-recorded mobile phone call data collected at baseline (2007-2012) from participants in Denmark, Finland, the Netherlands, Sweden, and the UK. Parameter estimates obtained using simple, direct, and inverse RC methods were associated with less bias and lower mean squared error than those obtained with CC analysis or MI. We showed that RC methods resulted in more accurate estimation of the relation between mobile phone use and health outcomes, by combining self-reported data with objective operator-recorded data available for a subset of participants.

Comprehensive Inherited Risk Estimation for Risk-Based Breast Cancer Screening in Women.

PURPOSE: Family history (FH) and pathogenic variants (PVs) are used for guiding risk surveillance in selected high-risk women but little is known about their impact for breast cancer screening on population level. In addition, polygenic risk scores (PRSs) have been shown to efficiently stratify breast cancer risk through combining information about common genetic factors into one measure. METHODS: In longitudinal real-life data, we evaluate PRS, FH, and PVs for stratified screening. Using FinnGen (N = 117,252), linked to the Mass Screening Registry for breast cancer (1992-2019; nationwide organized biennial screening for age 50-69 years), we assessed the screening performance of a breast cancer PRS and compared its performance with FH of breast cancer and PVs in moderate- (CHEK2)- to high-risk (PALB2) susceptibility genes. RESULTS: Effect sizes for FH, PVs, and high PRS (>90th percentile) were comparable in screening-aged women, with similar implications for shifting age at screening onset. A high PRS identified women more likely to be diagnosed with breast cancer after a positive screening finding (positive predictive value [PPV], 39.5% [95% CI, 37.6 to 41.5]). Combinations of risk factors increased the PPVs up to 45% to 50%. A high PRS conferred an elevated risk of interval breast cancer (hazard ratio [HR], 2.78 [95% CI, 2.00 to 3.86] at age 50 years; HR, 2.48 [95% CI, 1.67 to 3.70] at age 60 years), and women with a low PRS (<10th percentile) had a low risk for both interval- and screen-detected breast cancers. CONCLUSION: Using real-life screening data, this study demonstrates the effectiveness of a breast cancer PRS for risk stratification, alone and combined with FH and PVs. Further research is required to evaluate their impact in a prospective risk-stratified screening program, including cost-effectiveness.

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.

Differences in mammography screening attendance among non-Western immigrants in Denmark, Finland, Iceland and Norway.

Several studies have shown that attendance rates are lower among non-Western immigrants than among natives. As the Nordic countries have quite similar health systems and populations but also differences in the organisation of their organised mammography screening programmes, differences in attendance rates could highlight organisational factors that might increase the attendance rates. Mammography screening is offered free of charge in Denmark and Finland, but not in Iceland and Norway. Contrarily to the other countries, Iceland do not send out pre-booked appointment. The study population included natives and non-Western immigrants aged 50-69 years, who had at least one invitation to the national mammography screening programmes in Denmark (2008-2017), Finland (2001-2017), Iceland (2001-2020) or Norway (2001-2015). Relative risks (RRs) of attendance were estimated and adjusted for age group and calendar period. The study population included 116.033 non-Western immigrants and more than 2 million natives. The attendance rates were significantly lower among non-Western immigrants than among natives, with an adjusted relative risk of 0.81/0.80 in Denmark and Finland, 0.62 in Norway, and 0.40 in Iceland. The lower attendance rates among immigrants in Norway and Iceland did not seem to be due to differences in birth country, immigration age, or educational level, but might be explained by organisational factors. Offering free-of-charge mammography screening in Norway and Iceland and/or including a pre-booked appointment in the invitation letters in Iceland might increase the attendance rate among non-Western immigrants.

Effect of Test History at Ages 50-64 on Later Cervical Cancer Risk: A Population-based Case-control Study.

As life expectancy increases, the effectiveness of cervical cancer screening programs needs to be reassessed for the older population. We addressed the effect of test history in and outside organized screening at age 50-64 years on later cervical cancer risk. A case-control study was conducted by deriving 229 cases of 65-79 years old women with invasive cervical cancer in 2010-2019 from the Finnish Cancer Registry. Ten controls were matched for each case by birth year and hospital district. The effect of test uptake and abnormal results in 50-64 year olds on cancer risk was investigated using conditional logistic regression and adjusted for self-selection. Test uptake within the 50-64 years age group showed 75% lower odds of cervical cancer [adjusted OR (aOR) = 0.25; 95% confidence interval (95% CI), 0.18-0.35]. Untested women had 4.9 times higher odds than those tested with normal results (aOR = 4.86; 95% CI, 3.42-6.92). Having at least one abnormal test result increased the odds by 2.5 when compared with only normal results but showed lower odds when compared with untested women. The importance of testing is exhibited by the result showing a reduction of odds of cancer to one-fourth for those tested compared with untested. Similarly, receiving abnormal results was protective of cancer compared with having no tests highlighting the importance of proper follow-up. Therefore, screening history should be considered when further developing cervical cancer screening programs with special interest in non-attenders and those receiving abnormal results at older ages. Significance: To our knowledge, this is the first study from Finnish data describing the effect of test history on later cervical cancer at older ages. Focusing on the cervical tests taken within the Finnish national screening program and outside it highlights the overall importance of having cervical tests and adds this study into the slowly increasing number of studies considering all cervical testing in Finland.

Cervical, liver and stomach cancer incidence and mortality in non-Western immigrant women: a retrospective cohort study from four Nordic countries.

BACKGROUND: Cervical, liver and stomach cancers are the most common infection-associated malignancies and the leading cause of morbidity in non-Western regions. We compared the incidence and mortality of these cancers between non-Western immigrant and non-immigrant Nordic female populations. We also analysed the effect of age at immigration, duration of residence and education on cancer burden. MATERIAL AND METHODS: Study population consisted of women residents in Denmark, Finland, Iceland and Norway in 1973-2020. Non-Western women contributed 3.1% of the total 260 million person-years at risk. All women were followed from their 20th birthday, or from the date of immigration if after, until the date of their first primary cancer diagnosis, death, emigration, or the end of the country-specific study period. All data were adjusted for 10-year age groups and calendar periods, and immigrant data was further broken down by region of birth, age at immigration and education level. Country-specific estimates were produced by multivariable Poisson regression and pooled in Finland with a random effects model. RESULTS: Altogether, there were 60 982 cases of cervical, liver and stomach cancer in the study population, causing 36 582 deaths. The immigrant women had significantly higher liver (rate ratio [RR] 1.78, 95% confidence interval (CI) 1.03-3.06) and stomach cancer incidence (RR 1.68, CI 1.29-2.18), and stomach cancer mortality (RR 1.49, CI 1.17-1.92) than non-immigrant women. In the immigrant population, high education was related to lower incidence and mortality of studied cancers. The rate ratio of cervical cancer decreased with duration of residence and increased with rising age at immigration. CONCLUSION: Due to the increased incidence and mortality of infection-related cancers and changes in cancer patterns by age at immigration and duration of residence, attention should be paid to targeted health care services for immigrants. Special efforts should be given to women who have spent their youth in high-risk areas.

A population-based cohort study on changes in breast, lung and colorectal cancer incidence and mortality among non-Western immigrant women.

BACKGROUND: Cancer risk varies geographically, and migrants are influenced by different risk factors before, during and after migration. Increased migration from non-Western countries to the Nordic countries calls for a better understanding of the migrants' cancer risk and the change in risk patterns over time. The aim of this study was to compare the incidence and mortality of breast, colorectal and lung cancer between non-Western immigrant and the native female population in Denmark, Finland, Iceland, and Norway. MATERIAL AND METHODS: Data from national registries were processed and pre-analysed in each country. Multivariate Poisson regression models were used to model the relative differences in incidence and mortality as rate ratios (RR). The country-specific estimates and summary statistics were pooled together using a random effects model. RESULTS: Non-Western immigrant women had significantly lower breast (RR 0.71, 0.65-0.78), colorectal (RR 0.72, 0.57-0.92) and lung (RR 0.55, 0.42-0.72) cancer incidence rates than native women, and the risk of these cancers among immigrant women increased with duration of residence. Differences were parallel in breast, colorectal and lung cancer mortality (RR 0.64, 0.55-0.74; RR 0.66, 0.48-0.92; RR 0.51, 0.34-0.79). Among immigrant women, higher education increased the risk for breast cancer and decreased it for lung cancer. CONCLUSION: The results significantly complement and add to the previous findings of cancer burden and cancer burden transition among migrants and provide evidence of a prolonged cancer risk advantage among non-Western immigrant women. However, the findings show an increasing risk of lifestyle-related cancers with increasing duration of residence in the host country. Further studies are needed to discover underlying reasons for this phenomenon.

Flexible transition probability model for assessing cost-effectiveness of breast cancer screening extension to include women aged 45-49 and 70-74.

Breast cancer is the most common cancer among Western women. Fortunately, organized screening has reduced breast cancer mortality. New recommendation by the European Union suggests extending screening with mammography from 50-69-year-old women to 45-74-year-old women. However, before extending screening to new age groups, it's essential to carefully consider the benefits and costs locally as circumstances vary between different regions and/or countries. We propose a new approach to assess cost-effectiveness of breast cancer screening for a long-ongoing program with incomplete historical screening data. The new model is called flexible stage distribution model. It is based on estimating the breast cancer incidence and stage distributions of breast cancer cases under different screening strategies. The model parameters, for each considered age group, include incidence rates under screening/non-screening, probability distribution among different stages, survival by stages, and treatment costs. Out of these parameters, we use the available data to estimate survival rates and treatment costs, while the modelling is done for incidence rates and stage distributions under screening policies for which the data is not available. In the model, an ongoing screening strategy may be used as a baseline and other screening strategies may be incorporated by changes in the incidence rates. The model is flexible, as it enables to apply different approaches for estimating the altered stage distributions. We apply the proposed flexible stage distribution model for assessing incremental cost of extending the current biennial breast cancer screening to younger and older target ages in Finland.

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.

What can We Learn From High-Performing Screening Programs to Increase Bowel Cancer Screening Participation in Australia?

BACKGROUND: Colorectal cancer (CRC) is the second most diagnosed cancer in men and women and second most common cause of cancer death in Australia; Australia's CRC incidence and mortality are among the world's highest. The Australian National Bowel Cancer Screening Program began in 2006; however, only 33% of those approached for the first time by the Program between 2018 and 2019 returned the kit. Of the 5.7 million kits sent during this period, only 44% were returned. Our aim was to identify practices and features of national bowel cancer screening programs in countries with similar programs but higher screening participation, to identify potential interventions for optimising Australian CRC screening participation. METHODS: We searched published and grey literature for CRC screening programs reporting at least 50% screening participation using postal invitation and free return of iFOBT home kits. Interviews were conducted with cancer registry staff and academic researchers, focused on participant and practitioner engagement in screening. RESULTS: National programs in Netherlands, Scotland, Denmark, and Finland reported over 50% screening participation rates for all invitation rounds. Shared characteristics include small populations within small geographic areas relative to Australia; relatively high literacy; a one-sample iFOBT kit; national registration systems for population cancer screening research; and screening program research including randomised trials of program features. CONCLUSIONS: Apart from the one-sample kit, we identified no single solution to persistent Australian low uptake of screening. Research including randomised trials within the program promises to increase participation. IMPACT: This screening program comparison suggests that within-program intervention trials will lead to increased Australian screening participation.

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.

Health inequalities among Russian-born immigrant women in Finland: Longitudinal analysis on cervical cancer incidence and participation in screening.

Research has documented both lower and higher cancer incidence among migrants. Evidence among the large Russian-born migrant population, however, is scarce. We examined cervical cancer incidence and screening participation among Russian-born immigrant women in Finland, a country with complete cancer registration and universal public health care including organized cancer screening. Our study population included all the women that resided in Finland during 1970-2017 and was formed linking individual-level data from four nationwide registries. The linked data sets on cancer and cancer screening were analysed separately using different statistical models. Russian-born immigrant women had increased (+62%) incidence of cervical cancer compared to the general Finnish female population, and they participated in cervical cancer screening slightly less than other women. Our findings showed no consistent transition pattern in cancer incidence or screening participation rate with duration of stay. Potential explanations for the observed differences include institutional and behavioural factors. Cervical cancer is one of the most preventable cancers, and cancer screening can both prevent and reduce incidence and mortality of cervical cancer. Efforts should be made to encourage migrant populations to participate in cervical screening.

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.

Sociodemographic features and patterns of non-participation in colorectal cancer screening in Finland.

BACKGROUND: Colorectal cancer (CRC) screening was run as a randomized health services programme in Finland between 2004 and 2016. This study evaluates sociodemographic features and patterns of non-participation among men and women invited to be screened. METHODS: The study population in this register-based study includes 233 211 men and women invited to guaiac faecal occult blood test screening on consecutive screening rounds (n = 708 621 invitations). A generalized estimating equation (GEE) was used to estimate incidence rate ratios (IRR) between sociodemographic features and non-participation. RESULTS: The overall proportion of non-participation was 31.6% and was higher in men (38.8%) than in women (24.6%). Birth cohort, education, marital status and country of birth were associated with non-participation. The birth cohort of 1950-54 was less likely to participate than the birth cohort of 1940-44. Men and women with primary education were more likely non-participants (IRR 1.26, CI 1.23-1.29 and IRR 1.22, CI 1.18-1.26, respectively) than men or women with tertiary education. Further, unmarried persons and immigrants had an increased risk of non-participation. Initial non-participation predicted subsequent behaviour, since, e.g. ∼80% of first-round non-participants also remained non-participants in the second round. CONCLUSION: Education, gender and marital status had a significant effect on non-participation in the CRC screening programme. As high and comprehensive participation is essential for a successful screening programme, attention should be paid in ensuring participation of all sociodemographic groups. Special efforts should be invested in those not participating in the first invitational round, since initial non-participation predicts non-participation to subsequent invitations.

Extending Age Ranges in Breast Cancer Screening in Four European Countries: Model Estimations of Harm-to-Benefit Ratios.

The main benefit of breast cancer (BC) screening is a reduction in mortality from BC. However, screening also causes harms such as overdiagnosis and false-positive results. The balance between benefits and harms varies by age. This study aims to assess how harm-to-benefit ratios of BC screening vary by age in the Netherlands, Finland, Italy and Slovenia. Using microsimulation models, we simulated biennial screening with 100% attendance at varying ages for cohorts of women followed over a lifetime. The number of overdiagnoses, false-positive diagnoses, BC deaths averted and life-years gained (LYG) were calculated per 1000 women. We compared four strategies (50-69, 45-69, 45-74 and 50-74) by calculating four harm-to-benefit ratios, respectively. Compared to the reference strategy 50-69, screening women at 45-74 or 50-74 years would be less beneficial in any of the four countries than screening women at 45-69, which would result in relatively fewer overdiagnoses per death averted or LYG. At the same time, false-positive results per death averted would increase substantially. Adapting the age range of BC screening is an option to improve harm-to-benefit ratios in all four countries. Prioritization of considered harms and benefits affects the interpretation of results.

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.