Journal of Medical Screening

To quantify changes in the proportion of women aged 35 and older choosing serum screening for Down’s syndrome over time and the effect on false positive and detection rates.

From Rhode Island hospital-based laboratory prenatal screening records (2013–2017) we extracted the test performed (Integrated, Combined, Quadruple), maternal age, and Down’s syndrome risk; documented observed changes in maternal age distributions and false positive rates, and modelled the impact of varying proportions of older women choosing screening on each test’s performance using the 2015 United States birth cohort as baseline.

Over five years, observed false positive rates for Integrated testing declined from 1.9 to 1.3% (−32%). The proportion of older women tested declined from 14.9 to 8.5%, from which modelling predicts a 16% decline in the false positive rate. This is lower than our observed change but consistent with a reduction driven by declining participation by older women. Modelling predicted a detection rate reduction from 89 to 87%. Larger detection rate impacts were predicted for Combined and Quadruple testing.

This study documents, for the first time, the declining proportion of older women choosing Down’s syndrome serum screening and subsequent impact on screening performance. The American College of Obstetrics and Gynecology recommends offering cell-free DNA screening for these ‘high risk’ pregnancies and uptake may increase further. Screening programmes could consider increasing use of Integrated testing over other serum screening tests or lowering risk cut-offs so false positive rates approach those of 2012 to regain lost detection.

Beta thalassaemias are a group of hereditary red cell disorders resulting in a reduced or absent production of the main adult haemoglobin, adult haemoglobin. In England, the NHS Sickle Cell & Thalassaemia Screening Programme recommends reporting newborn beta thalassaemia disease as an incidental finding when detected whilst screening for sickle cell disease. The current action value to initiate further investigations is 1.5% adult haemoglobin, using high-performance liquid chromatography or capillary electrophoresis. We examined the reliability of this action value.

A 44-month country-wide prospective study using data from 13 newborn screening laboratories in England.

There were 81 cases reported with an adult haemoglobin of 1.5% or less at first-line screen, of which nine were lost to follow-up. The six false-positive results were all of 32 weeks’ gestation or less. Of the 66 true-positives, 36 had confirmatory molecular results (11 of these cases also have results from tandem mass spectrometry), 19 had clinical confirmation and 11 had the results of both parents available which were consistent with the screening result. There was one false-negative, a confirmed beta thalassaemia major case with an adult haemoglobin of 1.7%, above the action value at first-line screen but known to be at risk from parental results and therefore referred into clinical care by the laboratory.

This study demonstrates a positive predictive value of 91.7%, with a specificity of 99.9% and a sensitivity of 98.5%. These results confirm the reliability of the current action value.

To integrate child–parent screening and cascade testing into a single pathway-child-parent cascade screening (CPCS), for the identification of familial hypercholesterolaemia in the population and to estimate the number of new familial hypercholesterolaemia cases identified per child screened and the associated costs.

We applied the results from the published MRC Child–Parent Screening Study to 10,000 children, together with cascade testing first degree relatives of parents with a familial hypercholesterolaemia mutation identified by child–parent screening. We estimated the number of familial hypercholesterolaemia cases identified per child screened, the median cost per familial hypercholesterolaemia case identified and the median cost per child screened to identify one case using a range of cholesterol and familial hypercholesterolaemia mutation testing costs. We present a case study to illustrate the application of CPCS in practice.

CPCS identifies one new familial hypercholesterolaemia case per 70 children screened at a median estimated cost of £960 per new familial hypercholesterolaemia case or £4 per child screened. CPCS identifies an average of four new familial hypercholesterolaemia cases per family. In the case study, six new familial hypercholesterolaemia cases were identified, and preventive treatment started in five, with the index child expected to start when older.

CPCS for familial hypercholesterolaemia are complementary strategies. The sustainability of cascade testing relies on identifying new unrelated index cases. This is achieved with population-wide child–parent screening. Integrated CPCS is currently better than either method of familial hypercholesterolaemia detection alone. It has the potential to identify all, or nearly all, individuals with familial hypercholesterolaemia in the population at low cost.

Several European countries are implementing organized colorectal cancer (CRC) screening programmes using faecal immunochemical test (FIT) and/or flexible sigmoidoscopy (FS), but the cost-effectiveness of these programmes is not yet available. We aimed to assess cost-effectiveness, based on data from the established Piedmont screening programme.

Using the Piedmont programme data, a Markov model was constructed comparing three strategies in a simulated cohort of 100,000 subjects: single FS, biennial FIT, or sequential strategy (FS + FIT offered to FS non-responders). Estimates for CRC incidence and mortality prevention were derived from studies of organized screening. Cost analysis for FS and FIT was based on data from organized programmes. Incremental cost-effectiveness ratios (ICER) between the different strategies were calculated. Sensitivity and probabilistic analyses were performed.

Direct costs for FS, and for FIT at first and subsequent rounds, were estimated as €160, €33, and €21, respectively. All the simulated strategies were effective (10–17% CRC incidence reduction) and cost-effective vs. no screening (ICER <€1000 per life-year saved). FS and FS + FIT were the only cost-saving strategies, with FS least expensive (€15 saving per person invited). FS + FIT and FS were the only non-dominated strategies. FS + FIT were more effective and cost-effective than FS (ICER €1217 per life-year saved). The residual marginal uncertainty was mainly related to parameters inherent to FIT effectiveness and adherence.

Organized CRC screening programmes are highly cost-effective, irrespective of the test selected. A sequential approach with FS and FIT appears the most cost-effective option. A single FS is the least expensive, but convenient, approach.

Population-based cancer screening has been described as a teachable moment for behaviour change. This research examined the effect of faecal occult blood testing (FOBT) participation on smoking, alcohol consumption, fruit and vegetable consumption and physical activity.

Data were from screening-naïve men within the English Longitudinal Study of Ageing, receiving their first FOBT invitation (n = 774). Four waves of data were included in analyses (wave 4, 2008/2009 – wave 7, 2014/2015). Baseline data were from the wave prior to FOBT invitation, and follow-up data were from the next consecutive wave (two years later).

The effects of FOBT participation, time and group-by-time interactions on health behaviours were investigated using generalised estimating equations. Almost two-thirds of the sample (62.5%; n = 484) had participated in FOBT.

Screening participants were less likely to smoke (odds ratio (OR): 0.45, 95% confidence interval (CI): 0.29–0.68) and more likely to meet fruit and vegetable consumption guidelines (OR: 1.70, 95% CI: 1.14–2.55). Smoking decreased over time (OR: 0.74, 95% CI: 0.62–0.89), but adherence to alcohol guidelines also decreased (OR: 0.71, 95% CI: 0.53–0.91). A group-by-time interaction was found for vigorous physical activity; the odds of taking part in vigorous physical activity increased for FOBT participants, but decreased for non-participants (OR: 1.40, 95% CI: 1.01–1.95).

This research provides tentative support for FOBT as a teachable moment for increasing vigorous physical activity. However, overall, there was limited evidence for spontaneous improvement in multiple health behaviours following participation.

Using quantitative Faecal Immunochemical Test (FIT) in colorectal cancer screening enables adjustment of the cut-off for a positive test. As men have higher stool blood levels and higher prevalence of colorectal neoplasia, different cut-off levels can be chosen for men and women. We evaluated participation and positivity rates switching from guaiac-based faecal occult blood test (gFOBT) (Hemoccult®) to FIT (OC-Sensor), using gender-specific cut-offs.

The colorectal cancer screening programme of Stockholm-Gotland, Sweden, started in 2008 and invited individuals aged 60–69 to biennial testing using gFOBT. From 1 October 2015 the test was switched to FIT, with positivity cut-offs of 40 (200) and 80 (400) µg Hb/g (ng/mL) faeces for women and men, respectively. The first year was evaluated for compliance and positivity, number of reminders and incorrect/inadequate tests, compared with gFOBT in the preceding 12-month period.

There were 127,030 and 87,269 individuals invited to screening with gFOBT and FIT, respectively. The change of test increased overall participation by 11.9% (95% confidence interval 11.5%–12.3%) from 56.5% to 68.4% (p < 0.001). The increase was larger in men (14.3%) than women (9.7%), and in those aged 60–64 (14.2%) than those aged 65–69 (8.7%). The positivity rate was 2.6% in women and 2.5% in men. There was a lower rate of reminders and incorrect/inadequate tests with FIT.

Within a well-organised colorectal cancer screening programme, changing the test from gFOBT to FIT markedly increased participation, especially among men, and in the younger age group. With a lower cut-off in women than men, the positivity rate was similar.

A large proportion of women have a preference for a same-gender endoscopy practitioner. We tested how information about practitioner gender affected intention to have bowel scope screening in a sample of women disinclined to have the test.

In an online experimental survey, women aged 35–54 living in England who did not intend to participate in bowel scope screening (N = 1060) were randomised to one of four experimental conditions: (1) control (practitioner’s gender is unknown), (2) opposite-gender (male practitioner by default), (3) same gender (female practitioner by default), and (4) active choice (the patient could choose the gender of the practitioner). Intention was measured following the interventions.

Of 1010 (95.3%) women who completed the survey, most were White-British (83.6%), and working (63.3%). Compared with control, both active choice and same-gender conditions increased intention among disinclined women (9.3% vs. 16.0% and 17.9%; OR: 1.85; 95% CI: 1.07–3.20 and OR: 2.07; 95% CI: 1.23–3.50). There were no differences in intention between the opposite-gender and control conditions (9.8% vs. 9.3%; OR: 1.06; 95% CI: 0.60–1.90) or the active choice and same-gender conditions (16.0% vs. 17.9%: OR: 0.89; 95% CI: 0.55–1.46, using same gender as baseline).

Offering disinclined women a same-gender practitioner, either by choice or default, increased subsequent intention, while an opposite gender default did not negatively affect intention. Reducing uncertainty about gender of practitioner could positively affect uptake in women, and should be tested in a randomised controlled trial.

Cervical cancer mortality has halved in Australia since the national cervical screening program began in 1991, but elevated mortality rates persist for Aboriginal and Torres Strait Islander women (referred to as Aboriginal women in this report). We investigated differences by Aboriginal status in abnormality rates predicted by cervical cytology and confirmed by histological diagnoses among screened women.

Using record linkage between cervical screening registry and public hospital records in South Australia, we obtained Aboriginal status of women aged 20–69 for 1993–2016 (this was not recorded by the registry). Differences in cytological abnormalities were investigated by Aboriginal status, using relative risk ratios from mixed effect multinomial logistic regression modelling. Odds ratios were calculated for histological high grade results for Aboriginal compared with non-Aboriginal women.

Of 1,676,141 linkable cytology tests, 5.8% were abnormal. Abnormal results were more common for women who were younger, never married, and living in a major city or socioeconomically disadvantaged area. After adjusting for these factors and numbers of screening episodes, the relative risk of a low grade cytological abnormality compared with a normal test was 14% (95% confidence interval 5–24%) higher, and the relative risk of a high grade cytological abnormality was 61% (95% confidence interval 44–79%) higher, for Aboriginal women. The adjusted odds ratio of a histological high grade was 76% (95% confidence interval 46–113%) higher.

Ensuring that screen-detected abnormalities are followed up in a timely way by culturally acceptable services is important for reducing differences in cervical cancer rates between Aboriginal and non-Aboriginal women.