20.04.06 Population screening - guidelines and ethics, future possibilities

Question 1

What is a population screening programme

Answer 1

Use of a simple test across an apparently healthy population in order to identify individuals who have risk factors or early stages of disease but do not yet have symptoms.

Question 2

Difference between genetic screening and testing

Answer 2

Screening targets populations/sub-populations rather than at-risk individuals to detect future disease risks in individuals/ progeny for which established preventive interventions exist (newborn screening for CF and PKU)

Question 3

What are the WHO criteria for genetic screening programmes

Answer 3

• Important public health burden in target population (i.e. not ultra rare)
• Natural history of disease is well understood
• General agreement (professionals, patients, community) on the benefits expected from the programme.
• A suitable test exists with known predictive value.
• Effective interventions exist to reduce morbidity and mortality among susceptible individuals
• Cost effective

Question 4

Who is responsible for screening procedures and policies in the UK

Answer 4

UK National Screening Committee (est 1996)

Question 5

What does the UK National Screening Committee do

Answer 5

Recommend the introduction of screening programmes following rigorous criteria for appraising the viability, effectiveness and appropriateness.

Question 6

Examples of population screening programmes

Answer 6

• Newborn blood spot screening (9 genetic conditions)
• Fetal anomaly screening programme (FASP)
• Down Syndrome screening
• NIPT
• Preconception carrier testing

Question 7

Review of newborn blood spot screening programme

Answer 7

• Series of biochemical/genetic tests carried out on blood spots taken from 5 day old babies.
• Conditions where there is benefit to early treatment.
• 9 conditions (sickle cell, CF, CAH, PKU, MCCAD, MSUD, IVA, GA1, HCU)

Question 8

What is the fetal anomaly screening programme

Answer 8

• Detailed ultrasound scan during pregnancy looking in detail at fetal anatomy.
• Invasive cytogenetic testing is offered if fetal abnormalities detected.

Question 9

What is the Royal college of Pathologists guidance on the use of prenatal microarrays

Answer 9

• 1 or more structural abnormality is identified by USS

- An isolated nuchal translucency greater than equal to 3.5mm (at 11 weeks- 13 weeks 6 days)

Question 10

What is the Down Syndrome screening programme

Answer 10

• Maternal blood test during pregnancy
• Biochemical markers associated with increased with of chromosomal abnormality in fetus
• Serum risk of greater than 1:150 is high risk, so invasive cytogenetic testing is offered.
• NIPT in future to reduce invasive tests

Question 11

What is preconception (or prenatal) carrier testing

Answer 11

• Carrier testing for recessive and X-linked conditions in general population or specific sub-populations at high risk.
• Preconception screening increases options available to couple vs prenatal testing
• e.g. CF, SMA
• Often involves a panel of most frequent sequence variants known to affect function.

Question 12

Issues behind screening for cancer susceptibility, e.g. breast cancer

Answer 12

• Pro: Cost effective as earlier diagnosis/ preventative treatment
• Cons: Low prior risk of women without family history (low prevalence of BRCA1/2 variants in general population compared to women with FH). Multifactorial nature of disease. Psychological harm to patients and effects of preventative surgery

Question 13

Possible detrimental effects of genetic screening

Answer 13

• Consenting newborns. Parents can opt out, needed to understand benefits so can make an informed decision.
• Carrier status identified in newborns.
• Results could cause anxiety, especially if no effective therapy or reduced penetrance.
• Social stigmatisation/discrimination
• Disclosure of information about family members who have not consented to testing.

Question 14

Future directions for population screenign

Answer 14

• More use of WGS/WES. e.g. PAGE study, prenatal exome sequencing when abnormalities detected
• cffDNA testing for Down syndrome (RAPID study)
• ctDNA for cancer screening.