Increasing coverage in cervical and colorectal cancer screening by leveraging attendance at breast cancer screening: A cluster-randomised, crossover trial.

BACKGROUND: Screening participation remains suboptimal in cervical cancer (CC) and colorectal cancer (CRC) screening despite their effectiveness in reducing cancer-related morbidity and mortality. We investigated the effectiveness of an intervention by leveraging the high participation rate in breast cancer (BC) screening as an opportunity to offer self-sampling kits to nonparticipants in CC and CRC screening. METHODS AND FINDINGS: A pragmatic, unblinded, cluster-randomised, multiple period, crossover trial was conducted in 5 BC screening units in the Central Denmark Region (CDR) between September 1, 2021 and May 25, 2022. On each of 100 selected weekdays, 1 BC screening unit was randomly allocated as the intervention unit while the remaining units served as controls. Women aged 50 to 69 years attending BC screening at the intervention unit were offered administrative check-up on their CC screening status (ages 50 to 64 years) and CRC screening status (aged 50 to 69), and women with overdue screening were offered self-sampling. Women in the control group received only standard screening offers according to the organised programmes. The primary outcomes were differences between the intervention group and the control group in the total screening coverage for the 2 programmes and in screening participation among women with overdue screening, measured 6 months after the intervention. These were assessed using intention-to-treat analysis, reporting risk differences with 95% confidence intervals (CIs). A total of 27,116 women were included in the trial, with 5,618 (20.7%) in the intervention group and 21,498 (79.3%) in the control group. Six months after the intervention, total coverage was higher in the intervention group as compared with the control group in CC screening (88.3 versus 83.5, difference 4.8 percentage points, 95% CI [3.6, 6.0]; p < 0.001) and in CRC screening (79.8 versus 76.0, difference 3.8 percentage points, 95% CI [2.6, 5.1]; p < 0.001). Among women overdue with CC screening, participation in the intervention group was 32.0% compared with 6.1% in the control group (difference 25.8 percentage points, 95% CI [22.0, 29.6]; p < 0.001). In CRC screening, participation among women overdue with screening in the intervention group was 23.8% compared with 8.9% in the control group (difference 14.9 percentage points, 95% CI [12.3, 17.5]; p < 0.001). Women who did not participate in BC screening were not included in this study. CONCLUSIONS: Offering self-sampling to women overdue with CC and CRC screening when they attend BC screening was a feasible intervention, resulting in an increase in participation and total coverage. Other interventions are required to reach women who are not participating in BC screening. TRIAL REGISTRATION: ClinicalTrials.gov NCT05022511. The record of processing activities for research projects in the Central Denmark Region (R. No.: 1-16-02-217-21).

Comparisons of assessment pathways after abnormal mammography screening in Denmark, Norway, and Spain.

PURPOSE: To ensure high-quality screening programmes and effective utilization of resources, it is important to monitor how cancer detection is affected by different strategies performed at recall assessment. This study aimed to describe procedures performed at recall assessment and compare and evaluate the performance of the assessment in Denmark, Norway, and Spain in terms of screen-detected cancer (SDC) and interval cancer (IC) rates. METHODS: We included women aged 50-69 years from Denmark, Norway, and Spain, who were recalled for assessment after screening mammography, and recorded all procedures performed during six months after diagnosis, and the timing of the procedures. Women were followed for two years and screen-detected and interval cancer, and sensitivity of recall was calculated and compared. RESULTS: In total, data from 24,645 Danish, 30,050 Norwegian, and 41,809 Spanish women were included in the study. Most of the women had some assessment within 2 months in all three countries. SDC rates were higher in Denmark (0.57) and Norway (0.60) compared to Spain (0.38), as were the IC rates, i.e. 0.25 and 0.18 vs. 0.12, respectively. The sensitivity of the diagnostic follow-up was somewhat higher in Denmark (98.3%) and Norway (98.2%), compared to Spain (95.4%), but when excluding non-invasive assessment pathways, the sensitivities were comparable. CONCLUSION: This comparison study showed variation in the assessment procedures used in the three countries as well as the SDC and IC rates and the sensitivity of recall.

Detection of colorectal cancer and advanced neoplasia during first surveillance interval after detection of adenomas in fecal immunochemical test cancer screening: a nationwide study.

BACKGROUND: Adenoma surveillance guidelines are based on non-fecal immunochemical test (FIT)-based screening settings. However, colorectal cancer (CRC) risk may be different in FIT-positive screening populations. We evaluated the CRC and advanced adenoma risk within the recommended surveillance periods in the Danish FIT-based CRC screening program for participants with intermediate or high risk adenomas according to 2010 European guidelines. Furthermore, we estimated CRC risk for those who were not recommended surveillance according to European Society of Gastrointestinal Endoscopy (ESGE) 2020 guidelines. METHODS: Using nationwide health registries, we identified 17 936 FIT-screening participants from 2014-2017 with adenomas undergoing surveillance (high risk 1 year, intermediate risk 3 years). Participants with a follow-up examination were included (N = 10 068). Relative risk (RR) of CRC and advance adenoma was compared between intermediate and high risk groups and between intermediates who were recommended surveillance (S) or no surveillance (NS) according to 2020 ESGE guidelines. RESULTS: During surveillance, CRC occurred in 0.59% of the high risk group and 1.11% of the intermediate risk group (RR 0.53 [95%CI 0.34-0.84]). The high risk group had a 24% increased risk of advanced adenoma. CRC occurred in 1.69% of the intermediateNS group and 0.87% of the intermediateS group (RR 1.94 [95%CI 1.18-3.21]), and RR for advanced adenoma was 1.19 (95%CI 1.03-1.37). CONCLUSION: CRC detection was lower among participants rated at higher risk at initial CRC screening. Findings at first screen-derived colonoscopy might not be as good a predictor of CRC risk in a FIT-positive screening population.

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.

Less Invasive Primary Treatment for Colorectal Cancer After Implementation of National Screening: A Nationwide Cohort Study.

BACKGROUND: The effect of organized colorectal cancer (CRC) screening on type of primary treatment remains sparsely investigated. This study evaluated the difference in primary treatment strategy between patients diagnosed with screen-detected (SD-CRC) and non-screen-detected colorectal cancer (NSD-CRC) in a national CRC screening program. METHODS: This was a retrospective national register-based cohort study. Data on patients aged between 50 and 75 years and diagnosed with SD-CRC or NSD-CRC were retrieved from the national colorectal cancer screening database and the Danish Colorectal Cancer Group database. Outcomes related to surgical invasiveness were compared between the two cohorts. Differences were expressed as relative risks using log-binomial generalized linear regression models. UICC stage IV specific outcomes were analyzed using the same method. All analyses were adjusted for sex, age, type of cancer (colonic/rectal), and Charlson comorbidity index. RESULTS: The study included 4707 patients with SD-CRC and 7328 with NSD-CRC. Therapeutic flexible endoscopy (SD-CRC: n = 636 vs. NSD-CRC: n = 334, RR: 2.50, P < 0.001), (robotic-assisted) laparoscopic resection ((n = 616 vs. n = 773, RR: 1.27, P < 0.001), n = 2759 vs. n = 3471, RR: 1.11, P < 0.001), and radical resection (n = 3890 vs. n = 4834, RR: 1.02, P = 0.002) were significantly more frequent in the SD-CRC group. The rates of emergency priority (n = 32 vs. n = 562, RR: 0.09, P < 0.001), open surgery (n = 391 vs. n = 1410, RR: 0.53, P < 0.001), supplementary organ resection (n = 259 vs. n = 860, RR: 0.56, P < 0.001), and stoma formation (n = 526 vs. n = 1040, RR: 0.89, P = 0.007) were significantly lower in the SD-CRC group. The rate of patients undergoing surgery with UICC stage IV disease was significantly higher in the SD-CRC group (SD-CRC: n = 262, NSD-CRC: n = 994, RR: 1.43, P < 0.001). CONCLUSION: SD-CRC remained associated with less invasive primary surgical treatment following adjustment for potential healthy user bias. UICC stage IV disease may be less advanced in patients with SD-CRC.

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.

Breast cancer screening and overdiagnosis.

Overdiagnosis is a harmful consequence of screening which is particularly challenging to estimate. An unbiased setting to measure overdiagnosis in breast cancer screening requires comparative data from a screened and an unscreened cohort for at least 30 years. Such randomised data will not become available, leaving us with observational data over shorter time periods and outcomes of modelling. This collaborative effort of the International Cancer Screening Network quantified the variation in estimated breast cancer overdiagnosis in organised programmes with evaluation of both observed and simulated data, and presented examples of how modelling can provide additional insights. Reliable observational data, analysed with study design accounting for methodological pitfalls, and modelling studies with different approaches, indicate that overdiagnosis accounts for less than 10% of invasive breast cancer cases in a screening target population of women aged 50 to 69. Estimates above this level are likely to derive from inaccuracies in study design. The widely discrepant estimates of overdiagnosis reported from observational data could substantially be reduced by use of a cohort study design with at least 10 years of follow-up after screening stops. In contexts where concomitant opportunistic screening or gradual implementation of screening occurs, and data on valid comparison groups are not readily available, modelling of screening intervention becomes an advantageous option to obtain reliable estimates of breast cancer overdiagnosis.

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.

Breast cancer mortality and overdiagnosis after implementation of population-based screening in Denmark.

INTRODUCTION: Service breast cancer screening is difficult to evaluate because there is no unscreened control group. Due to a natural experiment, where 20% of women were offered screening in two regions up to 17 years before other women, Denmark is in a unique position. We utilized this opportunity to assess outcome of service screening. MATERIALS AND METHODS: Screening was offered in Copenhagen from 1991 and Funen from 1993 to women aged 50-69 years. We used difference-in-differences methodology with a study group offered screening; a historical control group; a regional control group; and a regional-historical control group, comparing breast cancer mortality and incidence, including ductal carcinoma in situ, between study and historical control group adjusted for changes in other regions, and calculating ratios of rate ratios (RRR) with 95% confidence intervals (CI). Data came from Central Population Register; mammography screening databases; Cause of Death Register; and Danish Cancer Register. RESULTS: For breast cancer mortality, the study group accumulated 1,551,465 person-years and 911 deaths. Long-term breast cancer mortality in Copenhagen was 20% below expected in absence of screening; RRR 0.80 (95% CI 0.71-0.90), and in Funen 22% below; RRR 0.78 (95% CI 0.68-0.89). Combined, cumulative breast cancer incidence in women followed 8+ years post-screening was 2.3% above expected in absence of screening; RRR 1.023 (95% CI 0.97-1.08). DISCUSSION: Benefit-to-harm ratio of the two Danish screening programs was 2.6 saved breast cancer deaths per overdiagnosed case. Screening can affect only breast cancers diagnosed in screening age. Due to high breast cancer incidence after age 70, only one-third of breast cancer deaths after age 50 could potentially be affected by screening. Increasing upper age limit could be considered, but might affect benefit-to-harm ratio negatively.

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.

Effectiveness of Colorectal Cancer Screening in Detecting Earlier-Stage Disease-A Nationwide Cohort Study in Denmark.

BACKGROUND & AIMS: Most studies of the effectiveness of screening for colorectal cancer (CRC) using the fecal occult blood test tested the guaiac fecal occult blood test. However, the fecal immunochemical test (FIT) is now commonly used in screening. We aimed to evaluate the effectiveness of FIT-based screening for CRC on the number of incident CRC diagnoses and stage at diagnosis for individuals in Denmark who were invited for screening vs not yet invited. METHODS: We collected data for this register-based retrospective cohort study during the first 16 months of the prevalence round of a FIT-based CRC screening program (March 1, 2014 through June 30, 2015). A total of 402,826 residents of Denmark (50-72 years old) were randomly invited to undergo CRC screening within the study period, and 956,514 were invited thereafter. We obtained information on CRC diagnosis, date, and stage at diagnosis from the Danish Colorectal Cancer Group database. Cancer incidence per 100,000 invited/not yet invited individuals was calculated, along with the relative risk (RR) of CRC among invited compared with not yet invited individuals. RESULTS: CRC incidence during the study period was 339.4/100,000 invited individuals and 169.6/100,000 not yet invited individuals. CRC incidence increased with age among invited and not yet invited individuals. For invited women compared with not yet invited women, the RR of being diagnosed with stage I CRC was 3.39 (95% CI, 2.61-4.39), with stage II CRC was 2.16 (95% CI, 1.71-2.72), with stage III CRC was 1.37 (95% CI, 1.08-1.75), and with stage IV CRC was 0.92 (95% CI, 0.68-1.23). For invited men compared with not yet invited men, the RR of being diagnosed with stage I CRC was 3.71 (95% CI, 2.97-4.64); with stage II CRC was 2.26 (95% CI, 1.84-2.77), with stage III CRC was 1.88 (95% CI, 1.53-2.30), and with stage IV CRC was 1.20 (95% CI, 0.95-1.52). CONCLUSIONS: In analyzing data from a register-based cohort study in Denmark, we found that inviting individuals to undergo FIT-based CRC screening led to detection of almost 2-fold more cases of CRC than not inviting participants. The significant increase of CRC incidence among those invited for screening indicates a need for awareness of treatment capacity in countries introducing FIT-based CRC screening.

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.

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.