Session 6: Screening

Question 1

Describe Spontaneous Presentation and Opportunistic Case Finding in Detection of Disease

Answer 1

​Spontaneous Presentation

• Person presents with symptoms (self-defined as a patient) to GP, A&E or other services. CONTACT is SOUGHT.
• A diagnosis is made

Opportunistic Case Finding

• Person presents with symptoms related to a disease/problen
• GP takes opportunity to check for other diseases - BP measurement, Urine dipstick

Question 2

What is meant by diagnosis?

Answer 2

• Diagnosis: the definitive indentification of a suspected disease or defect by application of tests, examinations or other procedures (which can be extensive) to definitely label people as either having a disease or not having a disease. (2 separate, clear groups)
• Treatment will follow the diagnosis. The ‘patient’ will be prepared to accept the (reasonable) risks (side-effects) associated with the treatment in order to get well

Question 3

What is Screening?

Answer 3

• A systematic approach to detect an unrecognised condition by the application of tests, examinations or other procedures, which can be applied rapidly (and cheaply) to distinguish between apparently well persons who probably have a disease (or its precursor) and those who probably do not.
• NOT DIAGNOSIS
• Following screening, the person is labelled as “screen positive” - this does not mean that they definitely have the disease. Further tests are required before the diagnosis of disease is made (confirmation).
• Treatment will only follow once a definitive diagnosis is made.
• National Screening Committee’s Definition of Screening: Screning is a public health service in which members of a defined population, who do not necessarily percieve they are at risk of, or are already affected by a disease or its complications, are asked a question or offered a test, to identify those individuals who are more likely to be helped than harmed by further tests or treatment to reduce the risk of a disease or its complications.

Question 4

What is the Purpose of Screening?

Answer 4

• To give a better outcome compared with finding something in the usual way (having symptoms and self-reporting to health services).
• If treatment can wait until there are symptoms, there is no point in screening,.
• Finding something earlier is not the primary objective.
• Screening tests are usually less invasive than confirmation tests e.g. mammography in breast cancer is less invasive than fine needle aspiration, faecal occult blood is less invasive than colonoscopy in bowel cancer.
  *

Question 5

Describe AAA Screening

Answer 5

• Ruptured abdominal aortic aneurysm is responsible for the premature death of more than 4,000 men annually in England and Wales.
• Scheduled treatment of unruptured AAA low risk
• High risk for ruptured AAA
• All men in England are offered a single ultrasound screening scan when they are 64 (non-invasive).
• Benefit: reduces risk of death from rupture by about half

Risks

• 238 men need to be invited to screening to prevent one ruptured AAA in next 10 years. (You need to treat a lot of people in order to improve outcomes).
• Approximately 1 in 10,000 will attend for screeing, have a large AAA, and then undergo treatment which is complicated by death.
• Quality of life is impaired (at least short-term) for those who have treatment.
• Some cannot tolerate anxiety of knowing they have a small AAA.

Question 6

What is the four criteria for screening programmes?

Answer 6

• Disease / condition
• Test
• Treatment
• Programme

• Wilson and Junger, WHO 1968*
• National Screening Committee Criteria 2003*

Question 7

Describe the Disease/Condition Criteria

Answer 7

• Must be an important health problem
• Epidemiology and natural history must be well understood
• Must have an early detectable stage
• Cost-effective primary prevention interventions must have been considered and where possible implemented.

Question 8

Describe the Test criteria

Answer 8

• Simple and safe (screening healthy people)
• Precise and valid (‘tells the truth’)
• Acceptable to the population (VERY IMPORTANT e.g. faecal occult blood is not very acceptable to some people)
• Distribution of test values in the population must be known (i.e. the proportion who test positive and negative).
• An agreed cut-off level must be defined (who do we count as testing positive?)
• There must be an agreed policy on who to investigate further (i.e. the test positives)

Question 9

What is meant by False Positives and False Negatives?

Answer 9

• False Positives: well people are referred for further investigation. Puts them through stress, anxiety, inconvenience. Direct costs and opportunity costs. False positives = non-cases who test positive.
• False Negatives: screening programmes fail to refer people who do actually have an early form of the disease => inappropriate reassurance, possibly delay presentation with symptoms. False negatives = cases who test negative
• True Negative: doesn’t have disease, tests negative
• True Positive: does have the disease, tests positive

Question 10

What are the features of test validity?

Answer 10

Sensitivity (detection rate)

Specificity

Positive Predictive Value

Negative Predictive Value

Question 11

What is meant by Sensitivity?

Answer 11

• Is the proportion of the people with the disease who test positive - aka detection rate.
• Sensitivity is the probability a case will test positive
• = (A/ A+C) = (true positives)/ (true positives + false negatives)
• If the sensitivity is high then the test is very good at correctly identifying people with the disease you are screening for. A high sensitivity is ideal (although not always possible).

Question 12

What is meant by Specificity?

Answer 12

• Is the proportion of the people without the disease who test negative
• The proportion of the people who really do not have the disease who are identified correctly by the test as not having the disease
• Probability a non-case will test negative
• = (B/B+D) = (true negatives) / (false positives + true negatives)
• If the specificity is high then the test is very good at correctly identifying people without the disease as not having the disease.
• A high specificity is ideal (although not always possible).
• When the same test is applied in the same way in different populations, the test will have the same sensitivity and specificity.

Question 13

What is meant by Positive Predictive Value (PPV)?

Answer 13

• Patients want to know “If I am test positive Doctor, do I have the disease?”, “If I am test positive - what is my risk of actually having the disease?”
• Many people assume INCORRECTLY “that because I am test positive, I MUST have the disease.”
• PPV is the probability that someone who has tested positive actually has the disease.
• This value is strongly influenced by the prevalence of the disease. A low prevalence condiiton will have a lower PPV than a high prevalence condition, even if the sensitivity and specificity of the tests are the same.
• Breast cancer prevalance in around 0.6%. PPV is around 8%. For every case found, 11 women who have screened positive will have gone through unnecessary investigations.
• PPV = (a/a+b) = (true positives)/ (true positives + false positives)
• Prevalence = (a + c)/(a + b + c + d) = (true positives + false negatives) / (whole population)

Question 14

What is meant by Negative Predictive Value (NPV)

Answer 14

• NPV is the proportion of the people who are test negative who actually do not have the disease.
• The NPV is the answer to the question “If the screening test is negative, what are the chances that I really don’t have the disease?”
• NPV = (d/c+d) = (true negatives) / (false negatives + true negatives)

Question 15

What are the implications of false positive results?

Answer 15

• They will be offered (invasive) diagnostic testing with all its attendant anxieties and risks for a condition they actually do not have. They will be turned into patients, when they are not actually ill.
• May also lead to lower uptake of screening in future and greater risk of interval cancer.
• If the PPV is low, there will be a lot of people with false positive results who undergo stress and unnecessary procedures.

Question 16

What are the implications of false negative results?

Answer 16

• They will not be offered (invasive) diagnostic testing when in fact they may have benefitted from it. Their disease, although present will not be diagnosed.
• They will be falsely reassured - may present late with symptoms as a consequence.

Question 17

Describe the Treatment criteria

Answer 17

• Effective evidence based treatment must be available.
• Early treatment must be advantageous - you must not just bring forward the date of diagnosis (and not make a difference to outcomes - this does not help patients!)
• Agreed policy on whom to treat
• Clinical management of the condition and patient outcomes should be optimised in healthcare providers before participation in screening programme.

Question 18

Describe the Programme criteria

Answer 18

• Proven effectiveness (preferably with RCT data)
• Quality assurance for the whole programme not just the test.
• Facilities for counselling
• Facilities for diagnosis and treatment
• Has to be feasible and practical
• Other options should be considered e.g. improving treatment.
• Think about opportunity costs
• Decisions about parameters should be scientifically justifiable to the public.
• Benefit should outweight physical and psychological harm (test, diagnostic procedures or treatment
• Prostate cancer screening: in 10,000 men aged 50, 30 will die of prostate cancer. No evidence that screening would cut number of deaths. 4,200 would have ‘localised prostate cancer’, be offered surgery/radiotherapy (side effects) but for a condition that would have had no impact on life.

Question 19

What are the issues raised by screening?

Answer 19

1. Alteration of usual doctor-patient contract
2. Complexity of screening programmes
3. Evaluation of screening programmes
4. Limitations of screening
5. Sociological critiques of screening

Question 20

Describe the Alteration of the Usual Doctor-Patient Contract

Answer 20

• In clinical practice people self-present asking for help, so define themselves as patients (sick patient => doctor)
• Screening targets apparently healthy people who have not (actively) sought the help of the health service with the offer of help for something they may have never thought about. (doctor => healthy(?) person

Question 21

Describe the Complexity of Screening Programmes e.g. using Cervical cancer

Answer 21

Background

• Around 3,604 new cases of cervical cancer diagnosed in the UK in 2011
• 972 women died from cervical cancer in 2011
• Cervical cancer is the 12th most common cancer is women in the UK
• Cervical cancer is the most common cancer in women under 35 in the UK

NHS Cervical Screening Programme since 1988

• Not a test for cancer
• Method of preventing cancer by detecting and treating early abnormalities, which if untreated could lead to cervical cancer.
• Aims to reduce the number of women who develop invasive cervical cancer and the number of women who die from it.
• Free for women (25-64 years) every 3-5 years (England).
• NB: this is only applicable for England. Authorities in Wales, Scotland and NI have slightly different policies based on different interpretations of essentially the same evidence.

Question 22

Why not screen under 25s or over 65s?

Answer 22

​Why not screen under 25s?

• Under the age of 25, invasive cancer is extremely rare, but changes in the cervix are common
• Lesions that are destined to progress will still be screen-detectable and those that would regress will no longer be a source of anxiety (lots of false positives).
• Therefore avoid unnecessary investigations and treatments, anxiety, distress, etc.

Why not screen over 65s?

• Women aged 65 and over who have had 3 consecutive negative results are taken out of the call recall system.
• Natural history and progression of cervical cancer means it is highly unlikely that such women will go on to develop the disease.
• Women aged 65 and over who have never had a test are entitled to one.

Question 23

Describe the Cervical Screening Process and Results

Answer 23

​Cervical Screening Process

• Speculum to open up the vagina and then a spatula is used to “sweep” around the cervix and take a sample of cells from its surface.
• Head of the spatula broken into a small glass vial containing preservative fluid, or rinsed directly into the preservative fluid.
• Cytology lab grades to determine what happens next.

Cervical Screening Results

• Most results normal (approx 93% in 2013-2014) => continue routine screening
• Abnormal result = changes identified that may require further investigation. Not at all abnormalities need immediate treatment - need to strike a careful balance.
• Abnormal cells may be destroyed using laser ablation or cold coagulation, or may be cut away using loop diathermy or laser excision

Question 24

Describe the incorporation of HPV testing

Answer 24

• HPV vaccination introduced but also new triage role for HPV testing in screening (different types of HPV cause cervical cancer).
• HPV Sentinel Site Implementation Project reviewed how HPV testing could be used within screening.
• HPV triage for low-grade abnormalities rolled out from 2012.
• If HPV is present, then colposcopy referral.
• If HPV is absent, then returned to routine screening.

Question 25

What are the questions and debates in Cervical Screening?

Answer 25

* Is the natural history understood? * How many abnormalities would regress spontaneously? * Are the 'right' women being screened? Or is it only the worried well? * Debate over whether screening has caused reduction in mortality. * Over-treatment? * Psychological impact? Particularly as cervical cancer can be associated with sexual activity, sexual promiscurity

Question 26

Descibe Evaluating Screening Programmes

Answer 26

* Why evaluate? * Screening programmes must be based on good quality evidence? * There can be great pressure to start screening programmes e.g. prostate cancer however no robust evidence that earlier detection improves outcome.

Question 27

Evaluation Difficulty 1: What is Lead Time Bias?

Answer 27

* Early diagnosis falsely appears to prolong survival * Screened patients appear to survive longer but only because they were diagnosed earlier * Patients live the same length of time but longer knowing they have the disease - you are not changing when they're actually going to die

Question 28

Describe Evaluation Difficulty 2: What is Length time bias?

Answer 28

* Screening programmes better at picking up slow growing, unthreatening cases than aggressive, fast-growing ones. * Diseases that are detectable through screening are more likely to have a favourable prognosis, and may indeed never have caused a problem. * Could lead to false conclusion that screening is beneficial in lengthening the lives of those found positive - curing people that don't need curing?

Question 29

Evaluation Difficulty 3: What is selection bias?

Answer 29

* Studies of screening often skewed by 'healthy volunteer' effect. * Those who have regular screening likely to also do other things that protect them from disease. * An RCT would help deal with this bias

Question 30

Describe the Limitations of Screening

Answer 30

* National Screening Committee, 2010: "whilst screening has the potential to save lives or improve quality of life through early diagnosis of serious conditions, it is not a fool-proof process. Screening can reduce the risk of developing a condition or its complications but it cannot offer a guarantee of protection. In any screening programme, there is a minimum of false positive results (wrongly reported as having the condition) and false negative results (wrongly reported as not having the condition). THe UK NSC is increasingly presenting screening as risk reduction to emphasise this point)" **Need for informed choice** * Screening carries potential for harm as well as benefit * Increasing emphasis on promoting informed choice acout screening * However it can be very difficult to refuse screening as there are often incentives for GPs etc

Question 31

Describe the issues in Breast Screening with Mammography

Answer 31

Growing attention paid to the uncertainties and extent of over-diagnosis "no doubt that screening for breast cancer has limited benefit and some possibility of harm for an individual woman and marginal cost effectiveness for a community"; "it is thus not clear whether screening does more good than harm"

Question 32

Describe the Sociological Critiques of Screening

Answer 32

* Victim Blaming (structural critique) - Individuals encouraged to take responsibility for own health. - However due to socioeconomic differences etc, not everyone is equally able to do this * Individualising pathology (structural critique) - What about addressing underlying material causes of disease? * Surveillance Critiques - Individuals and populations increasingly subject to surveillance - Prevention part of wider apparatus of social control ("every so often you must present your body for inspection...") * Social Constructionist: health and illness practices can be seen as moral - give meaning through particular social relationships. * Feminist critique: is screening targeted more at women then men?