Widening the offer of human papillomavirus self-sampling to all women eligible for cervical screening: Make haste slowly.

Self-collection of samples for human papillomavirus (HPV) testing has the potential to increase the uptake of cervical screening among underscreened women and will likely form a crucial part of the WHO's strategy to eliminate cervical cancer by 2030. In high-income countries with long-standing, organised cervical screening programmes, self-collection is increasingly becoming available as a routine offer for women regardless of their screening histories, including under- and well-screened women. For these contexts, a validated microsimulation model determined that adding self-collection to clinician collection is likely to be cost-effective on the condition that it meets specific thresholds relating to (1) uptake and (2) sensitivity for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We used these thresholds to review the 'early-adopter' programme-level evidence with a mind to determine how well and how consistently they were being met. The available evidence suggested some risk to overall programme performance in the situation where low uptake among underscreened women was accompanied by a high rate of substituting clinician sampling with self-collection among well-screened women. Risk was further compounded in a situation where the slightly reduced sensitivity of self-sampling vs clinician sampling for the detection of CIN2+ was accompanied with lack of adherence to a follow-up triage test that required a clinician sample. To support real-world programmes on their pathways toward implementation and to avoid HPV self-collection being introduced as a screening measure in good faith but with counterproductive consequences, we conclude by identifying a range of mitigations and areas worthy of research prioritisation.

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.

Concurrent participation in breast, cervical, and colorectal cancer screening programmes in Denmark: A nationwide registry-based study.

Women in Denmark are invited to breast, cervical, and colorectal cancer screening in their fifties and sixties. We determined the patterns of concurrent participation in the three programmes. Participation in organised cancer screening was determined using the highly complete Danish population and health care registers for all women aged 53-65 years on 31 March 2018 who continuously resided in Denmark since 1 April 2012. Data were linked using unique personal identification numbers. We studied overall and cancer-specific proportions of women undergoing screening for all three, two, one, and none of the cancers. Among all 468,507 women, 406,306 (87%) participated in breast, 345,768 (74%) in cervical, and 316,496 (68%) in colorectal cancer screening. Despite high participation, only 255,698 (55%) women were screened for all three cancers, while 123,469 (26%) were screened for two, 54,538 (12%) for one, and 34,802 (7%) were not screened for any cancer. Cancer-specific patterns were highly heterogeneous across the population but changed little after accounting for women's medical history. A significant proportion of women who are screened for a specific cancer remain unscreened for other cancers. The consistency of these data at the international level requires a reconsideration of invitational practices for organised screening.

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.

Does full HPV genotyping perform similarly well in clinician-collected cervical samples and self-collected vaginal samples when using the CLART HPV4S assay?

BACKGROUND: Studies comparing self-collected vaginal samples with clinician-collected cervical samples with respect to high-risk human papillomavirus (HPV) detection and genotype agreement based on clinically validated full HPV genotype assays (e.g. the CLART HPV4S) are limited. This study compared the two types of samples using the CLART assay with respect to HPV detection and genotype agreement in a referral population. METHODS: A total of 212 women aged 30-59 years and diagnosed with atypical squamous cells of undetermined significance (ASC-US) within the Danish cervical cancer screening programme had a cervical sample taken at their general practitioner. Afterwards, the women took a vaginal sample with the Evalyn Brush device at home. The paired samples were HPV-tested with the full genotyping CLART HPV4S assay. Histological results, i.e. cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were available for 14 women with HPV-positive clinician-collected samples. RESULTS: The study found the same HPV prevalence in self-collected vaginal samples compared to clinician-collected cervical samples (19.3%, 95% CI 14.3-25.3% vs 18.4%, 95% CI 13.4-24.3%). The CLART HPV4S assay detected approximately the same number of CIN2+ cases in the self-collected vaginal samples compared to the clinician-collected cervical samples (13 vs 11 cases). Exactly the same genotypes were detected in 75% (21/28) of the HPV-positive paired samples, while at least one identical genotype was found in the remaining 25% (7/28) of the paired samples. CONCLUSIONS: The CLART HPV4S assay performed similarly well in self-collected vaginal samples as in clinician-collected cervical samples with respect to both HPV detection and genotype agreement when using the Evalyn Brush and the CLART HPV4S assay in a referral population. Although further evaluation is needed, the findings suggest that full HPV genotyping based on the CLART assay can be useful when establishing HPV genotype-specific referral strategies for women tested HPV-positive by self-sampling.

Varying fecal immunochemical test screening cutoffs by age and gender: a way to increase detection rates and reduce the number of colonoscopies.

BACKGROUND AND AIMS: Most colorectal cancer (CRC) screening programs based on the fecal immunochemical test (FIT) use the same cutoff value for all participants. This study aimed at finding age- and gender-specific cutoff values that can improve population-based CRC screening. METHODS: This observational study used data from the first 2 years of the Danish FIT-based CRC screening program to estimate sensitivity, specificity, number of positive tests, number of screen-detected cancers and adenomas, and number of interval cancers for various cutoff values for different male and female age groups. RESULTS: Data from 531,828 participants showed that lower cutoff values for older residents and higher cutoff values for younger residents increased the overall sensitivity and specificity, decreased the number of needed colonoscopies by 7%, increased the number of screen-detected cancer by 1.1%, increased the number of screen-detected adenomas by 5%, and decreased the number of interval cancers by approximately 1.5%. However, these cutoff values also increased an inequality in sensitivity and specificity. Choosing cutoff values that ensured equal sensitivity between the groups, however, did increase inequality in, for example, the interval cancer rate. CONCLUSIONS: In a FIT-based CRC program it is possible to decrease the number of needed colonoscopies while at the same time to increase overall sensitivity and specificity and detect more cancers and adenomas by using different cutoff values for different male and female age groups. However, this increases inequality in sensitivity and specificity, whereas other strategies like ensuring equal sensitivity could be considered.

Colorectal cancer screening participation among citizens not recommended to be screened: a cohort study.

BACKGROUND: Guidelines on colorectal cancer (CRC) screening recommend screening of average-risk adults only. In addition, screening of individuals with active inflammatory bowel disease (IBD) might result in too many false-positive cases. However, the organisers of CRC screening programmes are often uninformed of whom to exclude due to an elevated CRC risk or active IBD. It is therefore unknown how often high-risk individuals (i.e. individuals with a previous diagnosis of CRC or polyps associated with hereditary CRC syndromes and certain patient groups with a diagnosis of inflammatory bowel disease (IBD) or multiple polyps) and individuals with active IBD participate in CRC screening following invitation. MATERIALS AND METHODS: We used data from the first two years of the Danish CRC screening programme (2014-2015). Information on invitations, participations and FIT test results were obtained from the national screening database, while information on previous CRC, hereditary CRC syndromes, IBD or multiple polyps diagnoses were obtained from the Danish Cancer Registry and the Danish Patient Register. Screening participation rates and FIT-positive rates were calculated and compared for high-risk invitees, invitees having IBD and an average risk group of remaining invitees not diagnosed with colorectal polyps in 10 years preceding the invitation. RESULTS: When invited to CRC screening, 28-48% of high-risk residents (N: 29; 316; 5584) and 55% of residents with IBD (N: 2217; 6927) chose to participate. The participation rate was significantly higher (67%) among residents without previous colorectal disease, i.e. the average risk group (N = 585,624). In this average group 6.7% of the participants had a positive FIT test. The proportion of positive FIT results was higher among all disease groups (7.7-14.8%), though not statistically significant for participants with prior CRC diagnosis and participants with high-risk IBD. CONCLUSION: When high-risk residents and residents with IBD receive an invitation to CRC screening, many participate despite being recommended not to. The screening program was not intended for these groups and further research is needed as several of these groups have a higher rate of positive screening result than the average risk population.

Variations in pathways and resource use in follow-up after abnormal mammography screening: a nationwide register-based study.

PURPOSE: Mammography screening reduces breast cancer mortality, but a successful screening programme depends on both high participation and a sufficient follow-up of abnormalities. This study investigated patterns of follow-up after abnormal screening mammography in Denmark, and whether the variation was associated with health care resource use. METHODS: We included 19,458 women aged 50-69 years with an abnormal screening mammography during a 3-year period of 2014-2016. Women were followed until the end of 2018. Their follow-up pathway was categorized in terms of the timeliness, appropriateness (i.e. whether all recommended diagnostic tests were utilized), and the ratio of benign vs. malignant surgeries. Further, we estimated health care resource use including post-diagnostic imaging and surgery procedures. RESULTS: Ninety-seven percent of women had a diagnostic follow-up test within 6 months and 94% of those had diagnostic procedures in accordance with the recommendations. The proportion with timely follow-up (i.e. within 1 month) was 83%, but varied significantly between administrative regions (p < 0.001), and also between women with a screen-detected cancer and those with a false-positive mammogram (87% vs. 81%, p < 0.001). The ratio between having a benign versus a malignant surgery was 1:8, but it varied depending on which tests were used for diagnosis. The average number of procedures was, generally, in accordance with the recommendations. CONCLUSION: In most cases, follow-up after abnormal screening mammography followed national recommendations. We nevertheless found that this was not always the case in certain subgroups and administrative regions.

Gaps between recommendations and their implementation: A register-based study of follow-up after abnormalities in cervical cancer screening.

Follow-up after screen-detected abnormalities is crucial for the success of cervical cancer screening programs but is usually not closely monitored in official screening statistics. We determined how the follow-up deviated from the recommendations in the Danish organized program. Using Danish nationwide population-based registers, the follow-up pathways of 60,199 women aged 23-59 with non-negative screening samples from 2012 to 2014 were mapped until end of 2018. We studied the timeliness and appropriateness of follow-up tests after cervical cytology screening and the total resource use in accordance with the national recommendations. Regression analyses were used to determine variations in adherence according to age, provider type, region, and history of abnormalities. Among women referred for immediate colposcopy, 91.3% (95% CI: 90.9%-91.6%) attended within four months as recommended, whereas up to about half of the women with a recommendation for a repeat test received this test either too early or very late. Overall, only 43% (95% CI: 42.9%-43.7%) of women with non-negative screening tests received the recommended follow-up, whereas 18% (95% CI: 17.6%-18.2%) received more than was recommended, 35% (95% CI: 34.4%-35.1%) received some follow-up but less than recommended and 4% (95% CI: 3.9%-4.2%) were not followed up at all. These proportions varied by screening diagnosis, woman's age, type of health care provider, region, and history of abnormalities. On average, women underwent more tests of each type than recommended by the guidelines. Deviations from follow-up recommendations are very frequent even in organized cervical screening programs and should be routinely monitored by screening program statistics.

HrHPV testing vs liquid-based cytology in cervical cancer screening among women aged 50 and older: a prospective study.

INTRODUCTION: Evidence supports high-risk human papilloma virus (HPV) testing as the primary cervical cancer screening tool. However, benefits and harms should be carefully considered before replacing liquid-based cytology. In women age 50 and older, we evaluated how a commercially available DNA amplification HPV test compares with routine liquid-based cytology. METHODS: This prospective study included 4043 patients who had a cervical sample analyzed from September 2011 to September 2012. Patients were followed between 64 and 76 months (median: 70 months). Samples were analyzed using both liquid-based cytology and the Cobas 4800 HPV DNA test. We calculated the diagnostic efficacy of liquid-based cytology and HPV, with or without the opposite test as triage, using cervical intraepithelial neoplasia (CIN2+/CIN3+) as reference. RESULTS: The patients had a median age of 58 years, (range; 50-90). At baseline, HPV prevalence was 8.0%: a total of 3.7% of patients had atypical squamous cells of undetermined significance or worse (ASCUS+). Positive test results were 1.9% for liquid-based cytology with HPV triage and 3.0% for HPV with liquid-based cytology triage. The cumulative incidence of CIN3+ was 1.0% (40/4043). Sensitivities for CIN3+ were: liquid-based cytology 47.5% (31.5%-63.9%); liquid-based cytology with HPV triage 45.0% (29.3%-61.5%); HPV 90.0% (76.3%-97.2%); and HPV with liquid-based cytology triage 67.5% (50.9%-81.4%). Corresponding specificities were: liquid-based cytology 96.6% (96.0%-97.2%); liquid-based cytology with HPV triage 98.5% (98.0%-98.8%); HPV 92.8% (92.0%-93.6%); and HPV with liquid-based cytology triage 97.7% (97.2%-98.1%). At baseline, HPV testing overlooked five cases of gynecological cancer other than cervical cancer. Five cervical cancers were detected, two had been overlooked at baseline by liquid-based cytology and two by HPV testing CONCLUSION: HPV screening using DNA amplification is a promising alternative to liquid-based cytology in women age 50 and older, but evaluation of alternative triage methods is warranted. The risk of overlooking cancers needs consideration when replacing liquid-based cytology with HPV testing as a method for primary screening.

Potential for prevention: a cohort study of colonoscopies and removal of adenomas in a FIT-based colorectal cancer screening programme.

Introduction: Evidence suggests that colorectal cancer (CRC) screening using guaiac faecal occult blood tests (gFOBT) reduces the CRC burden by facilitating timely removal of adenomas. Yet, the faecal immunochemical test (FIT) is being implemented in many countries. The aim of this study was to analyse the risk of having adenomas detected when invited for FIT-based screening as compared to those not yet invited. Material and Methods: The study was designed as a register-based retrospective cohort study. The potential for prevention was estimated as number of individuals who had no adenomas, non-advanced adenomas, and advanced adenomas detected per 1000 invited/not yet invited individuals and the relative risk (RR) of each of the three outcomes. Results: A total of 1,359,340 individuals were included, 29.6% of whom had been invited and 70.4% had not yet been invited to participate in CRC screening. Compared with the not yet invited population, the invited group had a RR of no adenomas of 2.28 (2.22-2.34) and a RR of advanced adenomas of 7.41 (6.93-7.91). The RR of colonoscopy was 2.93 (2.87-2.99) for the invited population compared with the not yet invited population. Conclusion: The RR of having a colonoscopy was three times higher among those invited compared to those not yet invited for CRC screening and twice as often those who had been invited compared to those not yet invited had no adenomas detected. Still, the risk of advanced adenomas was more than seven times higher among the invited population, indicating that the screening programme holds great potential for reducing the CRC burden. Abbreviations: CI: Confidence interval; CRC: Colorectal cancer; FIT: Faecal immunochemical test; ICD: International Classification of Disease; RR: Relative risk.

The performance indicator of colonic intubation (PICI) in a FIT-based colorectal cancer screening program.

Objective: Cecal intubation rate (CIR) is known to be inversely associated with interval colorectal cancer (CRC) risk. Cecal intubation may be achieved by the use of force and sedation jeopardizing patient safety. The Performance Indicator of Colonic Intubation (PICI) is defined as the proportion of colonoscopies achieving cecal intubation with use of ≤2 mg midazolam and no-mild patient-experienced discomfort. We aimed (i) to measure the variation of PICI between colonoscopists and colonoscopy units; (ii) to assess the correlation between the individual components of PICI; and (iii) to evaluate the association between PICI and commonly used performance indicators. Materials and methods: For the period 1 July 2015 through 30 June 2017 of the prevalent round of the Danish FIT-based CRC screening program, we included colonoscopies performed at four units in the Central Denmark Region within 60 days after a positive FIT-test. The PICI variation was evaluated using rates and ranges. Correlations between individual PICI components were assessed using Pearson correlation coefficients. Polyp detection rate (PDR), Adenoma detection rate (ADR), Polyp retrieval rate (PRR) and Withdrawal time (WT) were assessed within PICI quartiles. Results: The overall PICI was 78.7% with substantial variation between colonoscopists (40.0-91.9%) and units (72.6-82.0%). CIR was significantly correlated with patient-experienced comfort (r = 0.49, n = 73, p < .0001) and we observed that colonoscopists with a PICI between 79.9% and 84.3%) had the highest ADR. Conclusion: We found a substantial variation in PICI between colonoscopists and between colonoscopy units, which may reflect potential for quality improvements.

As you like it: How the same data can support manifold views of overdiagnosis in breast cancer screening.

Overdiagnosis estimates have varied substantially, causing confusion. The discussions have been complicated by the fact that population and study design have varied substantially between studies. To help assess the impact of study design choices on the estimates, we compared them on a single population. A cohort study from Funen County, Denmark, recently suggested little (∼1%) overdiagnosis. It followed previously screened women for up to 14 years after screening had ended. Using publically available data from Funen, we recreated the designs from five high-estimate, highly cited studies from various countries. Selected studies estimated overdiagnosis to be 25-54%. Their designs were adapted only to the extent that they reflect the start of screening in Funen in 1993. The reanalysis of the Funen data resulted in overdiagnosis estimates that were remarkably similar to those from the original high-estimate age-period studies, 21-55%. In additional analyses, undertaken to elucidate the effect of the individual components of the study designs, overdiagnosis estimates were more than halved after the most likely changes in the background risk were accounted for and decreased additionally when never-screened birth cohorts were excluded from the analysis. The same data give both low and high estimates of overdiagnosis, it all depends on the study design. This stresses the need for a careful scrutiny of the validity of the assumptions underpinning the estimates. Age-period analyses of breast cancer overdiagnosis suggesting very high frequencies of overdiagnosis rested on unmet assumptions. This study showed that overdiagnosis estimates should in the future be requested to adequately control for the background risk and include an informative selection of the studied population to achieve valid and comparable estimates of overdiagnosis.

Disaggregating the mortality reductions due to cancer screening: model-based estimates from population-based data.

The mortality impact in cancer screening trials and population programs is usually expressed as a single hazard ratio or percentage reduction. This measure ignores the number/spacing of rounds of screening, and the location in follow-up time of the averted deaths vis-a-vis the first and last screens. If screening works as intended, hazard ratios are a strong function of the two Lexis time-dimensions. We show how the number and timing of the rounds of screening can be included in a model that specifies what each round of screening accomplishes. We show how this model can be used to disaggregate the observed reductions (i.e., make them time-and screening-history specific), and to project the impact of other regimens. We use data on breast cancer screening to illustrate this model, which we had already described in technical terms in a statistical journal. Using the numbers of invitations different cohorts received, we fitted the model to the age- and follow-up-year-specific numbers of breast cancer deaths in Funen, Denmark. From November 1993 onwards, women aged 50-69 in Funen were invited to mammography screening every two years, while those in comparison regions were not. Under the proportional hazards model, the overall fitted hazard ratio was 0.82 (average reduction 18%). Using a (non-proportional-hazards) model that included the timing information, the fitted reductions ranged from 0 to 30%, being largest in those Lexis cells that had received the greatest number of invitations and where sufficient time had elapsed for the impacts to manifest. The reductions produced by cancer screening have been underestimated by inattention to their timing. By including the determinants of the hazard ratios in a regression-type model, the proposed approach provides a way to disaggregate the mortality reductions and project the reductions produced by other regimes/durations.

Benefit-to-harm ratio of the Danish breast cancer screening programme.

The primary aim of breast cancer screening is to reduce breast cancer mortality, but screening also has negative side-effects as overdiagnosis. To evaluate a screening programme, both benefits and harms should be considered. Published estimates of the benefit-to-harm ratio, the number of breast cancer deaths prevented divided by the number of overdiagnosed breast cancer cases, varied considerably. The objective of the study was to estimate the benefit-to-harm ratio of breast cancer screening in Denmark. The numbers of breast cancer deaths prevented and overdiagnosed cases [invasive and ductal carcinoma in situ (DCIS)] were estimated per 1,000 women aged 50-79, using national published estimates for breast cancer mortality and overdiagnosis, and national incidence and mortality rates. Estimations were made for both invited and screened women. Among 1,000 women invited to screening from age 50 to age 69 and followed until age 79, we estimated that 5.4 breast cancer deaths would be prevented and 2.1 cases overdiagnosed, under the observed scenario in Denmark of a breast cancer mortality reduction of 23.4% and 2.3% of the breast cancer cases being overdiagnosed. The estimated benefit-to-harm ratio was 2.6 for invited women and 2.5 for screened women. Hence, 2-3 women would be prevented from dying from breast cancer for every woman overdiagnosed with invasive breast cancer or DCIS. The difference between the previous published ratios and 2.6 for Denmark is probably more a reflection of the accuracy of the underlying estimates than of the actual screening programmes. Therefore, benefit-to-harm ratios should be used cautiously.

Body mass index and participation in organized mammographic screening: a prospective cohort study.

BACKGROUND: Breast cancer is the leading cancer among women, and early diagnosis is essential for future prognosis. Evidence from mainly cross-sectional US studies with self-reported exposure and outcome found positive association of body mass index (BMI) with non-participation in mammographic screening, but hardly addressed the influence of potential effect-modifiers. We studied the association between objective measures of BMI and participation in mammographic screening in a Danish prospective cohort, and explored the influence of menopausal status, hormone therapy (HT), previous screening participation, and morbidities on this relationship. METHODS: A total of 5,134 women from the Diet, Cancer, and Health cohort who were invited to population based mammographic screening in Copenhagen were included in analysis. Women were 50-64 years old at inclusion (1993-97) when their height and weight were measured and covariates collected via questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) for the association between BMI and mammographic screening participation were estimated by logistic regression, adjusted for other breast cancer risk factors and morbidities. Effect modification was evaluated by an interaction term and tested by Wald test. RESULTS: Underweight (BMI < 18.5 kg/m(2), OR: 95% CI; 2.24: 1.27-3.96) and obese women of class II (BMI 35-40 kg/m(2), 1.54: 0.99-2.39) and III (BMI ≥ 40 kg/m(2), 1.81: 0.95-3.44) had significantly higher odds of non-participation than women with normal weight. This association was limited to postmenopausal women (Wald test p = 0.08), with enhanced non-participation in underweight (2.83: 1.52-5.27) and obese women of class II and III (1.84: 1.15-2.95; 2.47: 1.20-5.06) as compared to normal weight postmenopausal women. There was no effect modification by HT, previous screening participation, or morbidities, besides suggestive evidence of enhanced non-participation in diabetic overweight and obese women. CONCLUSIONS: Underweight and very obese postmenopausal women were significantly less likely to participate in mammographic screening than women with normal weight, while BMI was not related to screening in premenopausal women. Effect of BMI on mammographic screening participation was not significantly modified by HT, previous screening participation, or morbidities.

Hysterectomy and its impact on the calculated incidence of cervical cancer and screening coverage in Denmark.

BACKGROUND: The incidence rates of cervical cancer and the coverage in cervical cancer screening are usually reported by including in the denominator all women from the general population. However, after hysterectomy women are not at risk anymore of developing cervical cancer. Therefore, it makes sense to determine the indicators also for the true at-risk populations. We described the frequency of total hysterectomy in Denmark and its impact on the calculated incidence of cervical cancer and the screening coverage. MATERIAL AND METHODS: With data from five Danish population-based registries, the incidence rate of cervical cancer and the screening coverage for women aged 23-64 years on 31 December 2010 were calculated with and without adjustments for hysterectomies undertaken for reasons other than cervical cancer. They were calculated as the number of cases divided by 1) the total number of woman-years from the general population; and 2) the at-risk population after exclusion of post-hysterectomy woman-years. Cases were defined as women with cervical cancer (incidence), or as women screened in the recommended interval, with or without adjustment for hysterectomies (coverage). RESULTS AND CONCLUSIONS: In 2010, the all-age prevalence of hysterectomy was estimated at 6%, and ≥ 16% at age ≥ 65. This translated into an overall 6% increase in the incidence rate of cervical cancer, from 12.8 (unadjusted) to 13.5 (adjusted) per 100,000 woman-years. The screening coverage increased from 76% (unadjusted) to 79% (adjusted). In Denmark, hysterectomies do not have a large overall impact on the calculated cancer incidence and screening coverage. Nevertheless, at ≥ 65 years adjusted rates would increase by almost 20% compared to unadjusted rates. This suggests that calculating disease risks per organ-years may have a role in understanding the true burden of the disease in a population at risk of developing that disease.

Is mammography screening history a predictor of future breast cancer risk?

Inspired by the model by Walter and Day for risk of cervical cancer following negative screens, one might hypothesize that women in a mammography screening programme with a certain number of negative screens had a lower remaining breast cancer risk than that of women in general. We studied whether number of negative screens was a predictor for a low remaining breast cancer risk in women participating in the mammography screening programmes in Stockholm, Copenhagen and Funen. Data were collected from the mammography screening programmes in Stockholm, Sweden (1989-2012), Copenhagen, Denmark (1991-2009) and Funen, Denmark (1993-2009), and linked to the respective cancer registries. We calculated cumulative hazard rates for breast cancer in women in cohorts defined by age at entry and number of negative screens for the maximum follow-up period in each screening centre. For all centres and cohorts, the cumulative hazard were parallel for all number of negative screens, from after the time, when the women were scheduled to be invited for the next screen. This means that the remaining breast cancer risk is similar no matter how many negative screens a woman have had. Number of negative screens was not a predictor of a low remaining breast cancer risk in women participating in the mammography screening programmes in Stockholm, Sweden, Copenhagen and Funen, Denmark. The history of previous negative screens is therefore not suitable for personalisation of mammography screening.

A simple way to measure the burden of interval cancers in breast cancer screening.

BACKGROUND: The sensitivity of a mammography program is normally evaluated by comparing the interval cancer rate to the expected breast cancer incidence without screening, i.e. the proportional interval cancer rate (PICR). The expected breast cancer incidence in absence of screening is, however, difficult to estimate when a program has been running for some time. As an alternative to the PICR we propose the interval cancer ratio ICR=intervalcancersintervalcancers+screendetectedcancers. We validated this simple measure by comparing it with the traditionally used PICR. METHOD: We undertook a systematic review and included studies: 1) covering a service screening program, 2) women aged 50-69 years, 3) observed data, 4) interval cancers, women screened, or interval cancer rate, screen detected cases, or screen detection rate, and 5) estimated breast cancer incidence rate of background population. This resulted in 5 papers describing 12 mammography screening programs. RESULTS: Covering initial screens only, the ICR varied from 0.10 to 0.28 while the PICR varied from 0.22 to 0.51. For subsequent screens only, the ICR varied from 0.22 to 0.37 and the PICR from 0.28 to 0.51. There was a strong positive correlation between the ICR and the PICR for initial screens (r = 0.81), but less so for subsequent screens (r = 0.65). CONCLUSION: This alternate measure seems to capture the burden of interval cancers just as well as the traditional PICR, without need for the increasingly difficult estimation of background incidence, making it a more accessible tool when evaluating mammography screening program performance.

The association of demographic and socioeconomic variables with cancer screening participation: A national cross-sectional study of three cancer screening programs in Denmark.

Objective: To analyze the demographic and socioeconomic determinants of non-participation in cervical, colorectal and breast cancer screening programs in Denmark. Study design and setting: We conducted a cross-sectional study involving all women aged 53-65 years residing in Denmark on March 31, 2018, utilizing comprehensive individual data from population registries. Logistic regression models were employed to assess associations between demographic and socioeconomic factors and non-participation compared with participating in one, two, and three cancer screening programs, presenting odds ratios (ORs) with 95 % confidence intervals (CIs). Both unadjusted and adjusted models were applied for each level of screening participation. Results: Significant associations with non-participation in the three cancer screening programs were observed across all demographic and socioeconomic covariates considered. Women with low incomes demonstrated the highest likelihood of non-participation (none vs. three programs attended, OR: 2.95, 95 % CI: 2.82-3.08). Similarly, increased odds of non-participation were noted among immigrants (Western immigrants: OR: 2.08, 95 % CI: 1.96-2.21; non-Western immigrants OR 1.26 95 % CI: 1.20-1.32), women living alone (OR: 2.08, 95 % CI: 2.02-2.14), women outside the labor force (OR: 1.92, 95 % CI: 1.86-1.99), and women with lower educational levels (OR: 1.44, 95 % CI: 1.39-1.50) in the model comparing non-participation to participating in three screening programs. A progressive intensification of the association with non-participation was noted with each incremental increase in screening participation (from one to two to three programs). Conclusions: Demographic and socioeconomic variables are significantly associated with non-participation in all three Danish cancer screening programs, particularly affecting women from vulnerable demographic and socioeconomic backgrounds. Future research should prioritize strategies to enhance participation within this subgroup, aiming to alleviate social inequities in cancer screening.