Journal of Medical Screening最新文献

Objective: A rolling circle amplification (RCA) based commercial methodology using cell-free (cf)DNA to screen for common trisomies became available in 2018. Relevant publications documented high detection but with a higher than expected 1% false positive rate. Preliminary evidence suggested assay variability was an issue. A multi-center collaboration was created to explore this further and examine whether subsequent manufacturer changes were effective.

Methods: Three academic (four devices) and two commercial (two devices) laboratories provided run date, chromosome 21, 18, and 13 run-specific standard deviations, number of samples run, and reagent lot identifications. Temporal trends and between-site/device consistency were explored. Proportions of run standard deviations exceeding pre-specified caps of 0.4%, 0.4% and 0.6% were computed.

Results: Overall, 661 RCA runs between April 2019 and July 30, 2022 tested 39,756 samples. In the first 24, subsequent 9, and final 7 months, proportions of capped chromosome 21 runs dropped from 39% to 22% to 6.0%; for chromosome 18, rates were 76%, 36%, and 4.0%. Few chromosome 13 runs were capped using the original 0.60%, but capping at 0.50%, rates were 28%, 16%, and 7.6%. Final rates occurred after reformulated reagents and imaging software modifications were fully implemented across all devices. Revised detection and false positive rates are estimated at 98.4% and 0.3%, respectively. After repeat testing, failure rates may be as low as 0.3%.

Conclusion: Current RCA-based screening performance estimates are equivalent to those reported for other methods, but with a lower test failure rate after repeat testing.

Objectives: To inform the development and evaluation of new blood-based colorectal cancer (CRC) screening tests satisfying minimum United States (US) coverage criteria, we estimated the impact of the different test performance characteristics on long-term testing benefits and burdens.

Methods: A novel CRC-Microsimulation of Adenoma Progression and Screening (CRC-MAPS) model was developed, validated, then used to assess different screening tests for CRC. We compared multiple, hypothetical blood-based CRC screening tests satisfying minimum coverage criteria of 74% CRC sensitivity and 90% specificity, to measure how changes in a test's CRC sensitivity, specificity, and adenoma sensitivity (sizes 1-5 mm, 6-9 mm, ≥10 mm) affect total number of colonoscopies (COL), CRC incidence reduction (IR), CRC mortality reduction (MR), and burden-to-benefit ratios (incremental COLs per percentage-point increase in IR or MR).

Results: A blood test meeting minimum US coverage criteria for performance characteristics resulted in 1576 lifetime COLs per 1000 individuals, 46.7% IR and 59.2% MR compared to no screening. Tests with increased CRC sensitivity of 99% ( + 25%) vs. increased ≥10 mm adenoma sensitivity of 13.6% ( + 3.6%) both yielded the same MR, 62.7%. Test benefits improved the most with increases in all-size adenoma sensitivity, then size-specific adenoma sensitivities, then specificity and CRC sensitivity, while increases in specificity or ≥10 mm adenoma sensitivity resulted in the most favorable burden-to-benefit tradeoffs (ratios <11.5).

Conclusions: Burden-to-benefit ratios for blood-based CRC screening tests differ by performance characteristic, with the most favorable tradeoffs resulting from improvements in specificity and ≥10 mm adenoma sensitivity.

Objectives: Cancer risk prediction may be subject to detection bias if utilization of screening is related to cancer risk factors. We examine detection bias when predicting breast cancer risk by race/ethnicity.

Methods: We used screening and diagnosis histories from the Breast Cancer Surveillance Consortium to estimate risk of breast cancer onset and calculated relative risk of onset and diagnosis for each racial/ethnic group compared with non-Hispanic White women.

Results: Of 104,073 women aged 40-54 receiving their first screening mammogram at a Breast Cancer Surveillance Consortium facility between 2000 and 2018, 10.2% (n = 10,634) identified as Asian, 10.9% (n = 11,292) as Hispanic, and 8.4% (n = 8719) as non-Hispanic Black. Hispanic and non-Hispanic Black women had slightly lower screening frequencies but biopsy rates following a positive mammogram were similar across groups. Risk of cancer diagnosis was similar for non-Hispanic Black and White women (relative risk vs non-Hispanic White = 0.90, 95% CI 0.65 to 1.14) but was lower for Asian (relative risk = 0.70, 95% CI 0.56 to 0.97) and Hispanic women (relative risk = 0.82, 95% CI 0.62 to 1.08). Relative risks of disease onset were 0.78 (95% CI 0.68 to 0.88), 0.70 (95% CI 0.59 to 0.83), and 0.95 (95% CI 0.84 to 1.09) for Asian, Hispanic, and non-Hispanic Black women, respectively.

Conclusions: Racial/ethnic differences in mammography and biopsy utilization did not induce substantial detection bias; relative risks of disease onset were similar to or modestly different than relative risks of diagnosis. Asian and Hispanic women have lower risks of developing breast cancer than non-Hispanic Black and White women, who have similar risks.

Objective: Early detection through mammographic screening and various treatment modalities of cancer may have changed life expectancy and cause-specific mortality of breast cancer patients. We aimed to determine the long-term cause of death patterns in screening-detected patients and clinically diagnosed patients in the Netherlands compared with the general population.

Methods: Using data from the Netherlands Cancer Registry and Statistics Netherlands of around 26,000 women, aged 50-75 at diagnosis and surgically treated for invasive breast cancer in 2004-2008, we compared patients with screening-detected and clinically diagnosed cancer for major causes of death until 2020. The expected number of all-cause and cause-specific deaths was calculated using rates of the general population.

Results: During the follow-up period, 4310 women died. The age-standardised all-cause mortality ratio for the screening-detected cancer group was 1.41 (95% confidence interval (95% CI), 1.37-1.46). A higher mortality ratio was observed for patients with clinically detected cancer: 2.27 (95% CI, 2.19-2.34). The observed versus expected breast cancer mortality ratio in the screening-detected patient group was 8.92 (95% CI, 8.45-9.40) and 20.23 (19.38-21.09) in the clinical group. Excess mortality was found for lung cancer in both patient groups, and small elevations for circulatory and respiratory disease in the clinically detected group.

Conclusion: Our results indicate that for the screening group no other causes of death but breast and lung cancer were prominent compared with the general population. The clinical group showed excess mortality for some other causes of death as well, suggesting a less healthy group compared with the general population.

Objectives: This study aimed to develop a risk-scoring model in the Scottish Bowel Screening Programme incorporating faecal haemoglobin concentration with other risk factors for colorectal cancer.

Methods: Data were collected for all individuals invited to participate in the Scottish Bowel Screening Programme between November 2017 and March 2018 including faecal haemoglobin concentration, age, sex, National Health Service Board, socioeconomic status, and screening history. Linkage with The Scottish Cancer Registry identified all screening participants diagnosed with colorectal cancer. Logistic regression was performed to identify which factors demonstrated significant association with colorectal cancer and could be used in the development of a risk-scoring model.

Results: Of 232,076 screening participants, 427 had colorectal cancer: 286 diagnosed following a screening colonoscopy and 141 arising after a negative screening test result giving an interval cancer proportion of 33.0%. Only faecal haemoglobin concentration and age showed a statistically significant association with colorectal cancer. Interval cancer proportion increased with age and was higher in women (38.1%) than men (27.5%). If positivity in women were mirrored in men at each age quintile interval cancer proportion would still have remained higher in women (33.2%). Moreover, an additional 1201 colonoscopies would be required to detect 11 colorectal cancers.

Conclusions: Development of a risk scoring model using early data from the Scottish Bowel Screening Programme was not feasible due to most variables showing insignificant association with colorectal cancer. Tailoring the faecal haemoglobin concentration threshold according to age could help to diminish some of the disparity in interval cancer proportion between women and men. Strategies to achieve sex equality using faecal haemoglobin concentration thresholds depend considerably on which variable is selected for equivalency and this requires further exploration.

Objectives: Hemoglobinopathies are the commonest inherited blood disorders and form a serious burden worldwide, affecting communities, patient quality of life and healthcare resources. The Kingdom of Bahrain has issued a law obligating couples to undergo premarital screening to detect those at risk of having children affected with these disorders. The aim of this study was to analyze the marital decisions of couples at risk for hemoglobinopathies and follow up the outcomes.

Methods: A retrospective study was conducted on couples at risk for hemoglobinopathies identified during the premarital screening program at local health centers in the Kingdom of Bahrain and referred to the genetics department in the Salmaniya Medical Complex for genetic counselling in 2018-2020.

Results: A total of 189 couples were found to be at risk for hemoglobinopathies, of whom 159 completed the survey. Of these, 107 (67%) decided to proceed with their marriage and 26 couples achieved pregnancy. Out of 24 at-risk pregnancies with known outcome, 83.3% were spontaneous whereas only 16.7% underwent in-vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD). Eight out of 20 infants born to couples after spontaneous conception were affected. A positive attitude toward IVF with PGD was held by 60% of at-risk couples.

Conclusions: Despite undergoing premarital screening and genetic counselling, a large percentage of at-risk couples proceeded with their marriage. Most of them justified their decision due to the availability of advanced methods that aid in the prevention of having an affected child. However, the cost of such intervention was a major barrier for the majority of couples.

Objectives: (a) To estimate the risk of recurrent cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+), lesions within 5 years of follow-up in human papillomavirus-negative/human papillomavirus-positive cohorts; (b) to assess whether certain risk factors can predict the recurrence of CIN2+/CIN3+ lesions; and (c) to provide recommendations for follow-up after treatment of cervical intraepithelial neoplasia, grade 2/3 to prevent cervical cancer.

Setting: Organized cervical cancer screening programme in Central Italy.

Methods: We included 1063 consecutive first excisional treatments performed between 2006 and 2014 for screening-detected cervical intraepithelial neoplasia, grade 2/3 lesions among women aged 25-65. The study population was divided into two groups according to the human papillomavirus test results performed 6 months after treatment: Human papillomavirus-negative and human papillomavirus-positive cohorts. The 5-year risk of developing cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+) was estimated using the Kaplan-Meier method and the Cox regression model.

Results: Among 829 human papillomavirus-negative and 234 human papillomavirus-positive women, six (0.72%; three cervical intraepithelial neoplasia, grade 2, three cervical intraepithelial neoplasia, grade 3) and 45 (19.2%; 15 cervical intraepithelial neoplasia, grade 2, 30 cervical intraepithelial neoplasia, grade 3), respectively, developed CIN2+ recurrence within 5 years of follow-up. The cumulative risks for CIN2+ and CIN3+ were 0.9% (95% confidence interval: 0.4%-2.0%) and 0.5% (95% confidence interval: 0.1%-1.4%), respectively, for the human papillomavirus-negative cohort, and 24.8% (95% confidence interval: 18.5%-32.7%) and 16.9% (95% confidence interval: 11.4%-24.5%), respectively, for the human papillomavirus-positive cohort. Risk factors associated with increased risk of recurrence were both margins positive for the human papillomavirus-negative cohort, and positive margins, cervical intraepithelial neoplasia, grade 3 lesions, high-grade cytology and high viral load for the human papillomavirus-positive cohort.

Conclusions: Human papillomavirus testing can identify women at increased risk of recurrence and this supports a recommendation for its use in the post-treatment follow-up of cervical intraepithelial neoplasia, grade 2/3 lesions.

Objectives: Cervical cancer elimination requires high-performance screening tests and high treatment rates, and thus high screening program performance is essential; however, Latin America lacks organized screening and quality assurance (QA) guidelines. We aimed to develop a core set of QA indicators suitable to the region.

Methods: We reviewed QA guidelines from countries/regions with highly organized screening programs and selected 49 indicators for screening intensity, test performance, follow-up, screening outcomes and system capacity. A regional expert consensus using the Delphi method in two rounds was implemented to identify basic indicators actionable within the regional context. The panel was integrated by recognized Latin American scientists and public health experts. They voted for the indicators blinded to each other based on feasibility and relevance. The correlation between both attributes was analyzed.

Results: In the first round 33 indicators reached consensus for feasibility but only 9 for relevance, without full coincidence. In the second round 9 indicators met the criteria for both (2 screening intensity, 1 test performance, 2 follow-up, 3 outcomes, 1 system capacity). A significant positive correlation was observed for test performance and outcomes indicators between the two attributes assessed (p < 0.05).

Conclusions: Cervical cancer control requires realistic goals supported by proper programs and QA systems. We identified a set of indicators suitable to improve cervical cancer screening performance in Latin America. The assessment by an expert panel with a joint vision from science and public health practice represents a significant progress towards real and feasible QA guidelines for countries in the region.

Many factors need to be considered when planning and managing a screening programme for the early detection of cervical cancer (CC). A non-systematic international review of the organisation of CC screening using high-risk human papillomavirus (HPV-HR) testing, aimed at identifying the organisational methods of these programmes, was conducted with a view to supporting the future of the French system in the context of the transition to HPV-HR testing. In countries where HPV testing has been implemented or planned, the initial reflection process has provided an opportunity to rethink the previous (cytological) screening organisation. Despite considerable differences between countries, a nationally or regionally centralised organisational model appears to be the preferred option in most countries. This model is based on a national/regional structure tasked with all invitations, reminders, follow-up and coordination, centralised laboratories integrating both biology and pathology laboratories, and a unified information system integrated with routine health management tools used by health practitioners and nurses. Besides quality considerations, grouped purchasing makes it possible to implement a public procurement policy that includes price negotiations with suppliers. Discussions around the introduction of HPV testing have resulted in most countries reviewing or creating information systems and quality assurance processes. While the WHO seems to recommend the systematic use of vaginal self-sampling, very few countries have considered this option. More and more countries are planning to implement vaginal self-sampling, but no clear organisational model has emerged from the countries where it has been implemented to date.