10. Screening Programmes

The aim of screening programmes is to find disease at an early and treatable stage but there are limitations to screening.
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The aim of screening programmes is to find disease at an early and treatable stage, to improve the prognosis, if not to cure it. However, it is not usually a “gold standard” diagnostic procedure that is used to screen, and so there will be false positives where concern is raised but there is no disease, and false negatives where people with the disease will be wrongly reassured. We discuss the benefits and limitations of screening as well as possible harmful effects. We look at the Wilson criteria for screening programmes and we examine many of the screening programmes that the NHS runs as well as mentioning private screening companies.

I have seen reports of a blood test to screen for 50 different cancers, that should be coming to clinics in the USA possibly as soon as 2021. However, I have seen little of substance about it. What is tested for in the blood? What are the 50 cancers? What is the rate of false positive and false negatives for each cancer? How much will it cost. These are all very important questions.

Politicians often see screening programmes as a panacea that will prevent disease, save lives and save the NHS vast sums. We look at how this compares with reality.

Screening and the Wilson Criteria

Screening is frequently misunderstood. Basically it aims to detect disease at an earlier stage than if it had been left to present naturally. This should improve prognosis and reduce the disease burden within the population. We tend to think of screening as being for cancers but screening may be for other diseases too.

It was very primitive compared to today

In the UK between 1945 and 1959 there was a programme called “mass x-ray” which involved taking miniature chest x-rays of the adult population to detect tuberculosis.1TB prevention and control The disease was quite common at the time and the first effective treatment was being developed. It helped the individual by earlier treatment and there was benefit to public health by reducing spread. The programme was also known as mass miniature radiography or MMR as small size chest x-rays were taken. The programme was stopped as the detection rate fell with success of the programme and a miniature chest x-ray gave a rather higher dose of radiation that a conventional full size one.

Screening can be for malignancies such as cervical cancer or breast cancer or for risk factors for coronary heart disease and strokes. Questionnaires have been developed to screen for alcoholism. When blood is collected by the blood transfusion service it is screened for diseases that could be passed to a recipient. Whatever type of screening is employed it requires certain principles called the Wilson criteria.2Principles and Practice of Screening for Disease This reference is from the World Health Organisation (WHO) in 1968 but it is still relevant to all screening.

  1. The condition that is being sought must be sufficiently common in the group being screened to make screening worthwhile.
  2. Screening will lead to earlier detection of a treatable disease so that the outcome is significantly improved.
  3. The screening technique has acceptable costs per case identified and the procedure is acceptable to both patients and staff.
  4. There will be a high enough uptake to make the procedure valid.
  5. There will be high specificity (low rate of false positives) and a very high sensitivity (very low rate of false negatives). Both these issues will be explained shortly.
  6. Investigation and management of positive results will not overburden the system.

To look at these in more detail:

  1. The condition being sought has to be sufficiently common to be worth bothering. This is not necessarily true of the whole population but only those who are being screened. Thus the NHS screens black people for sickle cell disease before anaesthesia but it is too rare in other races to be worth doing. Most cancers become more common with advancing years. The NHS bowel cancer screening programme used to start at the age of 60 but this is now reduced to 55 years old.
  2. There is no point in detecting a disease early if that does not improve prognosis. Chest x-rays as a screening test for lung cancer will fail to detect tumours smaller than 2 centimetres in diameter and at that size detection does not improve prognosis. There is no point in screening for dementia unless we can improve the outlook with the diagnosis.
  3. Money is an important consideration in the NHS or any other system. The programme has to offer value. This means that there must be an acceptable cost per case detected.
  4. If the technique is not acceptable to the patients and those who are called on to perform it there will not be adequate uptake. There are many reasons why people may find a screening procedure unacceptable. It may be argued that if people want to take up a screening procedure they will gain the benefit but if they do not that is their right and only they will suffer. If it is an infectious disease that is sought, then a poor uptake will still leave a large reservoir to infect others. In the early days of cervical smears, it tended to be the middle class, low risk women who took it up whilst lower class women who were at greater risk avoided it. This is an example of what is called the inverse care law. It means that those most in need of care are least likely to get it.
  5. Screening tests are not usually the “gold standard” test and so if a test is positive it needs to be further investigated; usually using the definitive test which may involve surgery. Specificity and sensitivity are very important issues. High specificity means a low rate of false positive tests. False positives are when the screening process suggests cause for concern but the patient does not have the condition. If it is too high it will unduly worry too many people who prove not to have the disease. It may mean unnecessary surgery and it puts too much strain on the hospital system that has to cope. Sensitivity has to be very high to keep an acceptable level of false negatives. This is when people are given a negative result but they actually have the disease. As well as being a personal tragedy it tends to put the screening test into disrepute to a greater extent than false positives.
  6. Investigation and management of positive results may involve hospital admission and surgery. There will be samples taken for laboratory analysis. Counselling about results and options may be required. It must not add unbearably to the routine work of the hospital.

The screening regimes given here are for the general population. For anyone at high risk, a different regime may well be appropriate. This includes women with a strong family history of breast cancer and screening for bowel malignancy in people with genetic conditions such as familial polyposis coli and inflammatory bowel disease.

Screening is a useful tool, but it is not without limitations.

Cervical Smears for Cancer of
the Cervix

This was the first mass screening process for any malignancy. It started in the NHS in the 1960s. It is almost unique in that other screening programmes usually aim to catch cancer at an early stage where the prognosis is better. This one looks for abnormalities that precede malignant change.

A speculum is passed which is an instrument that opens the vagina so that the cervix can be inspected directly and cells are scraped from it. They are smeared on to a microscope slide and stained by a technique developed in the early 1940s by George Papanicolaou, a Greek American pathologist. In the laboratory, they are examined under the microscope.3(Papanicolaou GN, Traut HF 1941) In honour of him, Americans call them Pap smears.

These cells have to be carefully examined for signs of

These are individual cells that are examined and not blocks of tissue. Hence it is called cytology and not histology. This is a very demanding job. The 4NHS cervical screening programme currently recommends that screening starts around the age of 25 and is repeated every three years to age 50 when, if there have been no abnormalities, it is repeated every five years to age 65 at which it can be stopped, again if there have been no abnormalities.

The colposcope has improved the management of borderline cases.

The cells may appear completely normal and a normal recall is advised. There may be abnormalities of the cells, especially the nuclei, but I shall not delve deeper into the types of abnormality except to state that depending upon the severity of the changes they may be classified as mild, moderate or severe dyskaryosis. An alternative classification is CIN I, CIN II or CIN III. CIN stands for cervical intraepithelial neoplasia. CIN and dyskaryosis are similar but not identical. For early stages the recommendation may be just to repeat the test in 3, 4 or 6 months’ time. Nowadays there may be a recommendation to inspect the cervix with an instrument called a colposcope to get a better picture at magnifications between x10 and x15 and possibly to treat suspicious areas. The colposcope permits direct inspection of the cervix under about x10 to x15 magnification.

A colposcope in use

Specific areas may be seen to take biopsies or to perform treatment. This is much more conservative and less damaging than a cone biopsy and much less likely to affect fertility. The next stage is called CIN IV or carcinoma-in-situ. The latter term refers to the condition when the cells look malignant but they have not yet started to invade which is the hallmark of malignancy. Strictly speaking carcinoma-in-situ is not a diagnosis that can be based on cytology which is the inspection of individual cells. Only with blocks of tissue is it possible to decide if invasion has occurred. This diagnosis calls for an operation called a cone biopsy. A truncated cone is excised from the cervix and checked by a pathologist to ascertain that abnormal cells do not extend beyond the border of the specimen and that there are no sign of invasive malignancy.

It may be wise to start screening earlier if there has been an early age of onset of sexual intercourse or multiple partners as these are risk factors and in such cases invasive malignancy can present before the age of 25. It may be continued past 65 if there have been recent abnormal smears. There is no point in screening virgins as they are not at risk and anyone who has had a total hysterectomy does not have a cervix to turn malignant. The ages for call and recall by the NHS system are a guide and earlier screening may be requested by those who are at increased risk.

“The unfortunate experiment” was a failure of research ethics and governance

A review from New Zealand looked at the natural history of abnormal smears if no action was taken.5Carcinoma in situ of the cervix and its malignant potential It referred back to what is often called “the unfortunate experiment.” This followed 576 patients with cervical carcinoma-in-situ. They reported that 75 showed persistent disease after various initial treatments but none developed invasive cancer during follow-up. This was severely criticised in a judicial review and it is often upheld as an example of bad and unethical science. The New Zealand review concluded that 20 to 30% of lesions progress to invasive carcinoma within 5 to 10 years. As no one knows which ones will remain static or even regress, and which ones will progress to overt malignancy, it is recommended that all should have the operation.

In 1975 the rate of cervical cancer in the UK was 7.5 per 100,000 women but by 2004 it had fallen by about 60% to 2.8 per 100,000. According to Cancer Research UK, by 2015 the number of cases of cancer of the cervix was 3,126 with 854 deaths in 2016. They say this gives a survival at 10 years of 63% which is very good. They add that from 2015 figures, 99.8% of cervical cancer cases were preventable.6Cancer Research UK This is very important.

Cervical smears have reduced deaths from the cancer

An analysis of mortality trends before and after the introduction of screening in the UK concluded that screening prevented an epidemic of cervical cancer and that the programme is likely to prevent approximately 5,000 deaths per year. This represents a saving of about £36,000 per life.7The cervical cancer epidemic that screening has prevented in the UK. Not only did the introduction of cervical screening see a fall in the death rates from cervical cancer but without it we may have expected a vast surge in the disease. In the 1960s sexual habits changed with the availability of oral contraceptives. Earlier intercourse and multiple partners were more common in “the permissive society” of the swinging sixties and without the need for barrier contraception the risk increased further. The introduction of the HPV vaccine should further decrease the burden of disease but as it covers only about 70% of the strains of virus that cause the disease the cervical smear programme will not be discontinued in the foreseeable future.

There have been a number of changes in the screening procedures since the 1960s. One is the frequency of call and recall which is currently as outlined above. In the UK the interval was every 5 years at first whilst in the USA smears were performed annually. Now they are much more similar, with evidence-based intervals but smears may be done at other times if indicated.

The instruments used to take the smears have changed to give a better chance of a good sample. An adequate sample is important to give a confident negative result. The skill of the person who takes the smear is far more important than the gender.

From left to right shows how spatulae and now brushes for smears have changed over the years.

Looking down the microscope all day to read cervical smears, looking for changes to cells that may indicate pre-malignant change is very demanding and it is not how many people would wish to spend their working days. However, computerised reading of smears with artificial intelligence (AI) is promising and it may offer an acceptable alternatives to humans.8Automated classification of Pap smear images Computer reading and artificial intelligence are promising but not yet the answer.9A review of image analysis and machine learning techniques for automated cervical cancer screening

The HPV vaccine is a vaccine against cancer

Another innovation or discovery that will be mentioned in much more detail in the section on Fake News and Vaccine Scares, is the role of the human papilloma virus (HPV) in initiating malignancy. There are many different strains of this virus but current vaccines protect against about 70%. However, the prevalence of HPV31, 33 and 45, the three types not covered by the vaccine, has also declined, suggesting the vaccine provides substantial cross-protection. This is a notable reduction but it does not make cervical smears redundant yet.

Trends in deaths from cervical cancer have been down in most countries in the world but in Japan there has been an increase. The trends in Japan may be attributable to increasing prevalence of human papillomavirus (HPV) infection among young women. Screening and vaccination have been shown to be highly effective and would help reverse these trends.10Increasing risk of uterine cervical cancer among young Japanese women

With such a scheme in place we may ask why cervical carcinoma is not a disease of the past. Any screening test has sensitivity, the number of false negatives; and specificity, the number of false positives. In view of the uncertainty about natural history it is inevitable that a significant number of false positives will occur. Cytology is the examination of individual cells and it cannot predict histology completely. Histology is the examination of blocks of tissue. This requires biopsies rather than scraping of cells.

False negatives are a problem that the public finds hard to accept. The skill of both the person who takes the smear and the one who interprets it are paramount. In the future, computerised reading of cervical smears may reduce errors. Failure to take an adequate sample will miss some abnormalities. A negative cervical smear can even occur with invasive cancer11Management of patients with invasive cervical cancer following a negative Pap smear and if the history or examination suggests malignancy a negative smear must not give reassurance. If the doctor or nurse who performs the smear thinks that the cervix looks suspicious of malignancy, a referral to a gynaecologist should be made. It is wrong simply to await the results of the smear as smears can be misleading. A biopsy to remove some tissue for examination must be done.

The commonest reason for dying of cervical cancer is failure to have a test

However, the commonest reason for failing to detect malignancy lies with the patient. A Canadian review of 42 studies found that smear frequency was the main factor leading to invasive cervical cancer. On average, 53.8% of invasive cervical cancer subjects had inadequate screening histories and 41.5% had never been screened. An estimated 29.3% of failures can be attributed to false-negative smears and 11.9% to poor follow-up of abnormal results. It is the young and the poorly educated who are most at risk.12Process of care failures in invasive cervical cancer Various techniques have been tried to improve compliance but with little or no effect. There is no easy answer as to how to encourage more women to have the test but it is an important issue that is worthy of the effort.

A case-control study from Sweden has reported that women who attended cervical cancer screening at recommended intervals have 20% of the risk of adenosquamous cell carcinoma (the common type) and a third the risk of rare types of invasive cervical carcinoma compared with women who did not attend screening as recommended.13Cervical screening and risk of invasive cervical carcinoma The authors explain that although the risk reductions are statistically significant the small number of cases reduces precision and precludes adjustment for lifestyle factors. An 80% reduction in risk is very impressive but it still means that invasive cancer can occur despite regular screening.

Screening for cervical cancer has been a great success story. It has reduced the incidence of the disease at a time when it might otherwise have been increasing. The vast majority of those who present with invasive disease have never been screened or have not been screened for many years. Fear and ignorance can be fatal. Hence it is of concern to find that the rate of uptake of cervical smears in the UK has fallen to around 70%.

An HPV self-test kit

A new screening process that is being investigated involves women taking samples from the vagina and urine specimens at home. They are tested for HPV infection. If this is positive, the more usual cervical smear or colposcopy will have to follow. This test is looking promising, but it is at a very early stage and it will need large trials to confirm its value before it is introduced. It is hoped that this self-test will improve the uptake of screening. It is said that around 25% of women who are invited for a smear do not attend. It appears that women are more coy these days and this might be a way to improve uptake. The roll-out has been started in early 2021.14Smear tests: Women to trial ‘do-it-at-home’ kits for NHS.

Nowadays, all women who have a smear test now have their samples examined first for human papillomavirus (HPV). This gives a more reliable picture of whether a woman may need treatment. If a sample is positive for the virus, it is tested to see if any of the cervical cells have undergone pre-malignant changes. This technique was introduced in stages across the country whilst it was evaluated but it is now used throughout the NHS. However, according to the BBC, there is a danger of women thinking that they have a sexually transmitted disease with all the stigma that involves. 15 HPV puts ‘strain’ on sex and dating Although the virus is transmitted by sexual contact, thinking of it along the lines of sexually transmitted diseases (STIs) is unfortunate and gives unnecessary connotations.

The HPV vaccine has produced a breakthrough despite covering only 70% of the variants of HPV that cause cancer. Since 2008 it has been offered to all school pupils when they are aged 12 or 13. It is available up to the age of 25. Rates of HPV infection have fallen by 86% among women aged 15 to 19, according to global research. This is expected to fall further now that the vaccine is given to boys too.

HPV rates have been falling

An analysis covering 60 million patients found that HPV rates in teenage girls had dropped by 83% across 14 countries between 2007 and 2015, with a 51% fall in those found to have pre-cancerous cells. 16 Cervical cancer is on its way to being eliminated The Times said that this was published in The Lancet in 2019 but I was unable to find it. It is hoped that elimination of cervical cancer is possible. This means that the numbers are very small, and it becomes a rare disease. Eradication is when a disease is completely wiped out and this has happened only for smallpox so far. However, it may take decades to achieve this goal and it can only be achieved if vaccination rates and screening rates are high.

Whilst NHS England and Public Health England have published an analysis of the success of the HPV programme, being very optimistic about the eventual elimination of cervical cancer, other sources have been more cautious.17Will HPV vaccination prevent cervical cancer? Cancer Research UK has warned that rates of cervical cancer screening in the UK have been stagnating since the mid-2000s. The uptake of the national cervical cancer screening programme has failed to rise over the last decade. Fewer than 75% of eligible women attend cervical screening, with even lower attendance among younger age groups and in more deprived regions. Reasons identified by the charity include embarrassment, fear of it hurting, feeling there is no need due to lack of symptoms or a perception of being at low risk.

Death rates from cervical cancer in Britain have fallen by 75% since the early 1970s and the number of new cases per year has fallen by 24% since the early 1990s. Of women who have the disease diagnosed, 63% survive for 10 years or more.

We still need cervical smears. There is no room for complacency. Ignorance kills

Mammography and the National Breast Screening Programme

Breast cancer is the commonest cancer in women. According to Cancer Research UK, in 2015 there were 55,122 cases of breast cancer and in 2016 there were and 11,563 deaths from the disease. This represents a 78% survival rate beyond 10 years.18Breast cancer statistics Breast cancer can affect men too but at about 390 cases per year, they represent rather less than 1% of cases. Men with breast cancer represent a different problem, and will not be considered further here.

The National Health Service Breast Screening Programme (NHSBSP) was the first of its kind in the world.19Breast screening programme overview It began inviting women for screening in 1990 and national coverage was achieved by the mid-1990s. There was some debate as to whether clinical examination should be added to mammography as it does increase the sensitivity but it was decided to opt for mammography only.

The Breast Screening Programme offers mammography every three years for all women in the UK aged 50 years and over. Around 1.5 million women are screened in the UK each year. Women aged between 50 and 70 years are routinely invited. After the age of 70 years, women may continue to have regular mammograms but they have to request it. Initially invitations were sent only to women aged 50 to 65 because it was thought that those over 65 would be unlikely to attend. After some pressure this has been extended to 70 years and it may be extended further. They are examining extending the age of invitation down to 47 and up to 73 but the research is still underway.

Mammography requires squeezing the breast which can be quite uncomfortable.

Women under 50 are not offered routine screening. Mammograms are more difficult to interpret in pre-menopausal women as the breast tissue is denser. The incidence of breast cancer is lower in this age group and repeated radiation to the breasts may even be a risk factor for malignancy. A review looked at the possible benefits of lives saved from early diagnosis versus possible induced cancer by the radiation over the years.20Radiation-Induced Breast Cancer Incidence and Mortality From Digital Mammography Screening: A Modelling Study It concluded that, on average, annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancers leading to 16 deaths relative to 968 breast cancer deaths averted by early detection from screening. Women with large breasts requiring extra views for complete breast examination and were projected to have higher radiation-induced breast cancer incidence. On balance, benefits seem to outweigh risks by around 7:1. This overview is based entirely on modelling.

The sensitivity (number of actual cases that are detected) is around 94%. This means that 6% of cancers are missed but rather than bemoaning the 6% missed we should applaud the 94% detected.

Magnetic resonance imaging (MRI) is being introduced to screen women with high-risk mutations in the genes associated with breast cancer. Some women are at very high risk as they carry the BRCA1 and BRCA2 mutations.21The clinical management of BRCA1 and BRCA2 mutation carriers They are a special group needing different considerations. Ultrasound may also be useful for denser breasts but its value for screening is unproven.

A mammogram unit

In England, the budget for the breast screening programme is around £75 million. This approximates to £37.50 per woman invited or £45.50 per woman screened. The cost is more than the mammography service as there is also the cost of dealing with positive findings whether true or false positives. The NHS Breast Screening Programme estimates that the programme is now saving 1,400 lives every year in England. This comes to just over £20,000 per quality added year of life (QALY). For more information on QALY see Basic Maths in Medical Research and Decision Making. The detection rate is higher in the older group who are not invited. This may be expected as they have a higher incidence than younger women and they may have requested mammography because there is breast cancer in their family. However, each case detected represents fewer quality added years than in younger women.22Cost effectiveness of the NHS breast screening programme The conclusion of that study was that the programme was borderline cost-effective but there was considerable doubt about the validity of the numbers.

It is estimated that 70% of the target population must attend to produce a reduction in mortality rates. Most cancers are discovered by the individual rather than at mammography and so breast awareness remains crucial.

Reading mammograms can be very difficult.

One of the great difficulties of the mammography service is the correct interpretation of the x-rays. Radiology is a speciality that has more difficulty recruiting than most. Each mammogram is supposed to be reviewed by two radiologists who are experienced in the field. Fortunately, this seems to be an area where artificial intelligence will allow computer reading of these films, giving accurate results.23Artificial Intelligence

As with any screening programme there are both benefits and problems:

  • A 20 year follow-up study found that screening with mammography reduces mortality from breast cancer by 23%.24Mammography service screening and mortality in breast cancer patients:
  • There are fewer mastectomies and more breast-conserving surgery in screened women who are diagnosed earlier.
  • In 2006/7 there were 13,443 cases of cancer diagnosed in women screened aged 45 and over. Of these, invasive cancers accounted for 10,484 (78.0 %). Of the invasive cancers detected 5,532 (52.8 per cent) were 15mm or less in size, and so would not have been detected by clinical examination.
  • Mammography is less sensitive in women receiving hormone replacement therapy (HRT) as their breasts are denser. Those who have been taking HRT for several years are also at higher risk.
  • The procedure of mammography is rather uncomfortable and this may cause refusal in the poorly motivated.
  • Over-diagnosis of breast cancer is the detection of cases that would never have come to clinical attention without screening. The rate of over-diagnosis of breast cancer in women aged 55 to 69 years has recently been shown to be 10%.25Rate of over-diagnosis of breast cancer Such cases may be false positive histological diagnoses. Some will arise when women are diagnosed by screening but then die shortly afterwards from other unrelated causes. Screening may also detect slow growing cancers that would not become symptomatic within the normal life expectancy. Over-diagnosis can lead to over-treatment.
  • There are about two false positive results from the screening procedure for every true case found.

The balance between benefits and harms of breast screening is more finely balanced than is generally thought.26Model of outcomes of screening mammography: information to support informed choices The expert committee advises that for every 400 women screened regularly over a 10 year period, one woman fewer will die from breast cancer than would have died without screening.

Among women who are routinely screened and diagnosed with breast cancer

  • 1 in 8 women would not have had their cancer diagnosed without screening.
  • 1 in 8 women would be spared the need for a mastectomy because of earlier detection.
  • 1 in 8 fewer women will die from breast cancer than would have died without screening.
Mobile units bring the service nearer the patient

On balance, it still seems to be a winner, but breast screening does have its critics. The ratio of benefits and risks are not as clear cut as some would suggest. A Cochrane review was not fully enthusiastic.27Screening for breast cancer with mammography The psychological effects of false positive mammograms should not be underestimated. The Cochrane review concluded, “If we assume that screening reduces breast cancer mortality by 15% and that over-diagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings.”

Women must understand the risks and benefits to make an informed choice

Women should have appropriate counselling or at least a clear and lucid leaflet before consenting. On balance, I would recommend it for those in the age to be called and, perhaps more so, for those who are older and need to request screening as their risk is higher.

A paper from Sweden in 2020 was more encouraging. It examined more than half a million women, representing approximately 30% of the Swedish population who were eligible for screening. Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years and a 25% reduction in the rate of advanced breast cancers.28Mammography screening reduces rates of advanced and fatal breast cancers This reduction was attributed to the screening programme and not to advances in the treatment of breast cancer.

Another paper from 2020 suggested that there is benefit from screening women from the age of 40.29Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial It concluded that reducing the lower age limit for screening from 50 to 40 years could potentially reduce breast cancer mortality. Mammography before the menopause can be more difficult as breasts are denser. The trial involved yearly mammography between the ages of 40 and 49 years. It found a “substantial and significant” 25% reduction in breast cancer mortality during the first 10 years of follow-up. The researchers calculated that 1150 women needed to undergo screening in the age group of 40 to 49 years to prevent one breast cancer death, or about one breast cancer death prevented per 1000 screened. However, the interpretation of this data has been questioned with critics claiming that it shows the exact opposite.30Breast cancer: study claiming that screening women in their 40s saves lives “found the opposite,” say critics

Women over 70 should request an appointment as they are not invited but risk increases with age

The other question relates to screening women who are older than 70. The incidence of breast cancer rises with age. My own practice audits of breast cancer screening showed that the rate of detection in older women was higher than in the younger ones who had been invited. I would recommend that women over 70 should request a mammogram. I think that the reason for not inviting older women is that it is felt that many would fail to attend. Perhaps they should be sent an invitation to request an appointment.

Screening for Bowel Cancer

Bowel cancer, also known as colo-rectal cancer or CRC, is the third commonest malignancy in both men and women and the fourth commonest overall. According to Cancer Research UK, there were 41,804 cases of bowel cancer in the UK in 2015. This affects about 23,000 men and 18,000 women each year representing about 14% and 11% of all cancers respectively. There were 16,384 deaths in 2016. The survival rate at 10 years is 57% but prognosis is markedly affected by the stage of the disease at diagnosis. Hence a programme to detect it early has much potential. They estimate that 54% of cases are preventable but this is due to known preventable risk factors rather than lack of screening.31Bowel Cancer Statistics

This shows the per cent of cancers found in each part of the colon

Testing strip for 3 days of stool samples

The NHS Bowel Cancer Screening Programme offers screening every two years to all men and women aged 60 to 74.32NHS Bowel Cancer Screening People over that age can request a screening kit. In 2018, Public Health England announced that the lower age for screening will be reduced to 50. The test involves the person taking small specimens of their bowel motions and scraping them on to a card. Two specimens from different parts of the motion are taken over three consecutive days. The specimens are tested for traces of blood. It is called faecal occult blood or FOB. Occult means hidden, not supernatural. People would not have reported it because they would not have noticed bleeding.

A new test is available but not in all areas. It offers flexible sigmoidoscopy to people at the age of 55 but it is available only in its initial pilot area. This part is not a national programme.33flexisig Note that this is sigmoidoscopy and not colonoscopy and so it checks out only the rectum and sigmoid colon. It does not go any higher. Sigmoidoscopy is an easier technique than colonoscopy as it does not require navigating so many bends. However, as the picture above shows, only 55% of cancers are found in the rectum and sigmoid colon. The other 45% are higher up.

A positive result will require further investigation by a colonoscopy. This involves adequate preparation of the bowel to empty it and then a fibre optic tube is passed up the anus to view the whole length of the large intestine.

A fibre-optic colonoscope has a light source and it can be manoeuvred in the bowel to inspect and to take biopsies

Cancer of the bowel is classified as Dukes’ stage A to D as the disease advances. Results from the first three years of screening showed that 1.9% of tests are positive, the rate increasing with age.34The first 3 years of national bowel cancer screening Cancer was identified in 1.62 per 1,000 people screened. There were 48% at Dukes’ stage A with only 1% found to have metastasises (secondary spread) at diagnosis. Of those with a positive screening test, 10.9% will have cancer and 35% an adenoma. This is usually a polyp which is not yet malignant, but there is high risk of malignant change. This is very encouraging as the prognosis deteriorates considerably with advancing disease, and if left to present normally, many people do not present until it is well advanced. As an adenoma may be seen as a pre-malignant condition, it means that of those with a positive screening test, nearly half will have significant pathology.

The above figures seem to suggest that screening for bowel malignancy with faecal occult bloods (FOB) is very satisfactory with a manageable level of false positives, cases being found at an earlier stage and a beneficial effect on death rates from the disease. However, it has examined only specificity or false positives, not sensitivity or false negatives. There is not a great deal of evidence on this but, where available, it is not encouraging. A German paper suggested that they miss more than 9 out of 10 advanced adenomas and 3 out of 4 cancers.35Diagnostic performance of guaiac-based fecal occult blood test in routine screening Another from France was no more encouraging.36Sensitivity of a colorectal cancer screening program based on a guaiac test For both papers the link goes to an abstract in English. Personally, I find these figures to be incredibly high and I do wonder how true they really are.

A small polyp can be snared or the base burned to destroy it before it turns malignant.

With regard to mammography, I wrote that it missed 6% of cases but we should rejoice in the 94% it identified. However, for bowel cancer, missing perhaps 75% of cases and detecting just 25% or less, does seem unacceptable and I wonder if it is really true. A Cochrane review has confirmed that this screening does reduce the mortality from bowel cancer.36Cochrane systematic review of colorectal cancer screening This suggests that despite the shortcomings, it is effective.

At the time of writing, in early 2019, there is a new test that should be in place in the next year and this will have a significantly better sensitivity and specificity. There will be fewer false positives due to such factors as too much red meat in the diet and there will be fewer false negatives or missed tumours. I must review the situation when the new system is established.

Christopher Robin and Winnie the Pooh play pooh sticks

The new bowel screening tool being introduced is called Faecal Immunochemical Test or FIT, to replace the standard sticks. It is thought to be more acceptable as it requires just one specimen, rather than two each day for three days. It is a type of faecal occult blood test which uses antibodies that specifically recognise human haemoglobin. It is used to detect, and can quantify, the amount of human blood in a single stool sample. An abnormal result suggests that there may be bleeding within the gastrointestinal tract that requires further investigation. Those with an abnormal result are then invited for further testing via a colonoscopy.

As it detects only human blood, it will not give false positives from meat. It gives a quantitative result and what will be accepted as requiring investigation can be adjusted with time, depending on results. Too high a level will result in missing disease. Too low a level will produce too many false positives.

NICE has produced guidelines for FIT, both as a screening tool and to investigate patients with symptoms.38NICE DG30

For conditions such as inflammatory bowel disease, where the risk of malignancy is rather higher than in the general population, screening is by colonoscopy at intervals depending on disease activity and recent history. Why, then, do we not use colonoscopy as our screening procedure for the general population? It is far more expensive per person to do colonoscopies than to mass produce the cards of faecal samples. There is time and the number of skilled staff involved. It may not be possible to recruit enough good endoscopists. Furthermore, having a colonoscopy rather than using the “pooh sticks” may be much less acceptable to many people with a resultant drop in the number of people who accept screening. Hence, this would fail to conform to a number of the Wilson Criteria for screening.

The Americans are keener on colonoscopy as a screening test

However, the Americans do seem to use colonoscopy as their screening procedure and it is done just once every 10 years. Rather as cervical smears aim to find premalignant lesions to treat before they become malignant, this aims to find adenomas rather than carcinomas. A study from Italy found that removing adenomas reduced carcinomas by 70 to 80%39colonoscopic polypectomy in reducing colorectal cancer incidence and a study of American veterans also found that despite a suboptimal uptake of screeing, colonoscopy reduced the number of cancers.40Colonoscopy and Colorectal Cancer Mortality in the Veterans Affairs Health Care System One day we may have colonoscopy as the screening procedure for the general population in the NHS. I think it is largely a matter of resources and acceptability.

The gut biome is very important in malignancy

Malignancy of the bowel is associated with an unhealthy gut biome. Biome means the bacteria in the gut. Certain species have been noted to be involved and a recent paper suggested that a new marker for a certain species called Lachnoclostridium may be a non-invasive screening process.41Fecal Bacterial Marker Noninvasively Diagnoses Colorectal Cancer However, this is at a very early stage. It may come to fruition some years from now, or it may fail to show promise and be discarded.

Prostate Cancer Screening

We have examined three screening procedures for cancer, two of which are exclusively for women. Now we shall examine one that is exclusively for men to see if it meets the needs.

According to Cancer Research UK, there were 47,151 cases of prostate cancer in the UK in 2015. This is 13% of all cancers. The incidence is 44% higher than in the 1990s.42Prostate cancer incidence statistics As expected, survival improves with early diagnosis. Cancer Research UK does not suggest why the incidence should be rising. The peak age at diagnosis is 75 to 79. I do not think that an aging population is a significant factor, but I suspect that the increasing prevalence of obesity is important as this is a known risk factor.

The figure below, from Cancer Research UK, shows that the condition is rare below the age of 50 after which the incidence rises sharply. The blocks give the number of new diagnoses but the line is important as it gives the rate of new cases. As age rises, the number of men in that age bracket falls and so incidence remains high.

The number of new cases falls from around 70 years old but the incidence remains almost unchanged as the number of men falls with advancing years.

According to an article in The Times in January 2020, 84% of men who have prostate cancer diagnosed are alive after 10 years, compared with 25% in the 1970s.43Prostate cancer deaths pass 12,000 to new high There were 48,561 cases and 12,031 deaths in 2017, compared with 47,864 cases and 11,307 deaths in 2014. Hence, new cases outnumber deaths from the disease by a little over 4:1, suggesting that 75% of men who have had the disease, die of something else. Figures from Prostate Cancer UK showed that only 47% were diagnosed at an early stage. It would seem that prostate cancer should be an ideal candidate for a screening programme.

PSA testing is not a reliable screen for cancer

There is a substance called prostate specific antigen (PSA) which is elevated in prostate cancer. Unfortunately a satisfactory test to fulfil the conditions of the Wilson criteria does not exist at present.44PSA-based screening for prostate cancer The difference between the range of normal and abnormal PSA in any age range shows far too much overlap to make it acceptable. Up to 15% of men with the cancer do not have an elevated PSA.45PSA testing Adding clinical examination does not improve the result. There has been a European Randomised Study of Screening for Prostate Cancer (ERSPC) and it did seem to show a 20% reduction in mortality. However, the rate of false positives was far too high. For breast cancer screening we have seen that there are about two false positive results for every true case found. In the prostate trial it was estimated that 48 men would have to receive investigation or treatment for prostate cancer to save one life.

Prostate screening with PSA and clinical examination has been used in the USA but it is falling from favour as the results are not good. Expert opinion in the USA is that it should no longer be used. A Cochrane review did not find it helpful.46Screening for prostate cancer

The management of an old man with a raised PSA is contentious

A further problem with the screening of prostate cancer is the question of the benefit of a diagnosis, especially in the elderly. Although 57% of prostate cancer deaths in the UK each year are in men aged 80 years and over, and mortality rates are highest over 90 years, there is still the question of what, if anything, to do for the patient.47Prostate Cancer (professional resource) Surgery or radiotherapy can produce incontinence and problems with sexual function. Do not write off sexual activity in the elderly. This effect on quality of life does them no favour if they would have died of something unrelated even if nothing had been done. Proton beam therapy is more accurate than megavoltage x-ray therapy and so does less collateral damage. However, there is one proton beam unit in London and another in Manchester for the entire NHS. Children with brain tumours are among those who will take priority for this scarce resource. It may well be that for elderly men with early disease, the best option is to watch and wait, sometimes called “masterly inactivity”. It is masterly as there is a great tendency to want to do something rather than nothing but nothing may be the best option. Simply monitoring in case of change may well be the best option.

Data from Cancer Research UK shows that screening by PSA greatly increases the number of investigations but does not reduce deaths

A study from London, but published in the American JAMA Oncology, compared prostate cancer screening by ultrasound and by MRI.48Population-Based Prostate Cancer Screening With Magnetic Resonance Imaging or Ultrasonography The ultrasound screening appeared to be no better than PSA testing but the MRI screening significantly increased the number of significant cancers found without increasing the number of negative biopsies that were taken. This seems very promising, if there are enough MRI facilities to offer a national prostate screening programme. It is also early days and more research is required.

A reliable urine test to screen for prostate cancer would be most welcome

Back in 2013, a review examined the use of urine specimens as a source of biomarkers for the early detection of prostate cancer and prediction of its prognosis.49Toward the detection of prostate cancer in urine: a critical analysis DNA, RNA, protein and metabolite-based biomarkers have been found in the urine. The review was optimistic. The urine was often collected after a rectal examination was performed as pressing on the prostate gland was thought to increase the amounts. An interesting innovation for screening for prostate cancer was reported in late 2019.50Methodology for the at-home collection of urine samples for prostate cancer detection It involved the collection of urine samples from men at home, so that they did not need to attend a clinic or to have a rectal examination.

In 2021, an article in The Times suggested that this is being taken further. It said that a simple home-testing kit could help to diagnose aggressive forms of prostate cancer up to 5 years earlier. The kits will be sent to 2,000 men in the UK, Europe and Canada as part of a trial. The men will take two urine samples to return by post for lab analysis. The aim of the Prostate Screening Box, as it is called, is to diagnose aggressive prostate cancer that will require treatment by looking at gene expressions in urine. In the pilot study it did so up to five years earlier than standard clinical methods, which means the need for invasive and uncomfortable tests would be reduced. This sounds very promising.

The PSA test as a screening test for prostate cancer does not meet the required criteria. I think that there are suitable screening tests in development but they are probably a few years away. They will be most welcome. For many men, a poorer stream and greater frequency is expected as they get older and it is not necessarily a sign of cancer. They may even develop back pain and just expect that too as a feature of age but it could be due to spinal secondaries. It is important to catch prostate cancer before it goes to bone as, once that happens, the prognosis is far worse. Until we get an adequate screening test, men must not be too reticent about presenting with urinary symptoms that may seem normal for their age. It could be prostate cancer. I know from personal experience.

Screening for Ovarian Cancer

Cancer of the ovaries is fairly common. Around 7,400 women are diagnosed with ovarian cancer in the UK each year and it is the sixth most common cancer in women.51Cancer Research UK It most commonly occurs in women in their 70s but it can strike rather younger. Unless it causes abnormal hormone production which may lead to postmenopausal bleeding, it tends to present with a swelling and so it usually is detected rather late.

Hence a technique to detect it early is attractive. Ultrasound screening would seem to be safe and acceptable. The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) was undertaken to determine if population screening can reduce deaths due to the disease. Participants were randomised to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening. The results of the randomised controlled trial were published in The Lancet in 2021.52Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Unfortunately, the interventions did not seem to reduce the number of deaths from ovarian cancer in either intervention group and so it cannot be recommended as a screening technique.

Abdominal Aortic Aneurysm Screening

The aorta is the large artery that carries blood from the heart down the body to be distributed to all parts. The last part of the aorta, just below the level of the umbilicus may suffer from dilatation that puts it at risk of rupture. The risk rises with age and it is much more common in men than in women. In 80% of cases of ruptured aneurysm there was no previous knowledge of the condition. If it can be diagnosed and treated before this happens the outcome is vastly better. Elective surgery to repair the aneurysm carries a mortality of less than 5%. Emergency repair of a leaking or ruptured aneurysm has mortality in excess of 60%.53Mortality from ruptured abdominal aortic aneurysm

1. arch of aorta. 2. left ventricle. 3. aneurysm of aorta. 4. descending aorta. 5. kidney.

The final part of the aorta can balloon out, obstructing blood flow to the lower limbs and kidneys. It can also rupture with catastrophic haemorrhage.

The screening procedure involves ultrasound examination to measure the diameter of the last part of the aorta. The NHS offers it to men only in the year that they turn 65. The incidence of the condition in women is so much lower that screening women is not justified. If there is no evidence of dilatation, no further action is taken as the risk of an aneurysm later in life is 1 in 1,000. If there is dilatation but it does not yet require treatment, there will be further appointments to monitor progress. An aneurysm of 5.5cms diameter or wider needs elective surgery. The programme is hoped to reduce death from ruptured aneurysm by up to 50% over 10 years.54Implementation of NHS Abdominal Aortic Aneurysm Screening A Cochrane Summary was supportive and said that it gave value for money.55Screening for abdominal aortic aneurysm We seem to have a screening test which is just for men which is cost-effective.

In March 2020, NICE altered its recommendations to include screening women aged 70 and over if AAA has not already been excluded on abdominal imaging and they have any of the following risk factors:56Abdominal aortic aneurysm: diagnosis and management

  • COPD
  • coronary, cerebrovascular or peripheral arterial disease
  • family history of AAA
  • hyperlipidaemia (eg raised cholesterol)
  • hypertension (high blood pressure)
  • they smoke or used to smoke

Screening and Interventions for
Coronary Heart Disease

Coronary heart disease is the commonest cause of death

Coronary heart disease is the commonest cause of death but we do not do population screening for it as such. Usually, anyone over 60 years old who is admitted to hospital for an operation has an ECG. This will show only fairly advanced disease. As we have seen in the section on Cohort or Longitudinal and Epidemiological Studies, research such as the Framingham studies, has given good evidence of what are the risk factors for coronary heart disease.

However, as was emphasised in that section, association and causation are not the same. Hence, to rectify a known risk factor will not necessarily reduce that risk if it is only a marker and not a cause. Suppose that you found that blonde people are more likely than brunettes to get sunburn. An intervention to dye blonde hair dark would affect the marker but it would not reduce their susceptibility to sunburn as the problem lies in the skin. Some of the early studies of the effects of lowering blood pressure were very disappointing but more recent ones have shown benefit. We have newer drugs and greater adherence to target blood pressure may explain this.

The following factors are known to be associated with an increased risk of coronary heart disease and stroke:

  • Genetics
  • Smoking
  • High blood pressure, more important for stroke than heart disease
  • Raised cholesterol, more important for heart, less for stroke
  • Diabetes
  • Obesity
  • Lack of exercise
  • High alcohol consumption

We do have evidence now that reducing blood pressure, as well as reducing cholesterol, stopping smoking, losing excessive weight and taking exercise are beneficial. Coronary heart disease (CHD) has a multifactorial risk, so it makes sense to address as many of these risks as possible.

Perhaps the most potent risk factor is genetics. If heart disease runs in the family, this is a strong risk factor. There may be a hereditary high cholesterol but not always, and a bad family history alone is a high risk factor. However, there is nothing that we can do about our genes. Hence, those at risk in that direction should be more stringent in avoiding other risk factors. Smoking is probably the most important modifiable risk. Health professionals may discuss it and offer support but it is up to the individual to take action.

Screening for hypertension is cost effective

High blood pressure does not normally cause any symptoms and so the only way to find it is to measure it. This is simple, non-invasive and easy. There are good, evidence-based guidelines on the diagnosis and management or hypertension (high blood pressure).57NICE Guidelines There is also evidence that treating hypertension reduces cardiovascular risk, although there are problems with failure to achieve target blood pressures and perseverance with treatment.58Arterial hypertension: benefits and limitations of treatment.

Unless we check cholesterol and blood pressure, people do not know if they have a problem.

Similarly, most people with raised cholesterol will be unaware. This is best tested with a fasting blood test. Nowadays we usually measure both high and low density cholesterol as low density is the bad cholesterol whilst high density is good cholesterol and gives protection. The figure that is taken is total cholesterol divided by high density cholesterol or TC/HDC. A class of drugs called stains are very effective in lowering cholesterol, usually without side-effects. Some are quite potent but being on statins does not mean that it is alright to eat injudiciously. There is a limit to what can be achieved with drugs, what can be achieved with diet alone or exercise and so it is wise to approach all aspects. Evidence suggests that reducing cholesterol reduces risk and there is no threshold below which there is no further benefit.59NICE Guidance is available.

It seems to be “the lower the better” for blood pressure too, provided that the person does not feel dizzy or faint on standing. Managing high blood pressure in the elderly is much more contentious. It is necessary to balance the benefits of reduction against the risk of dizziness on standing because blood pressure drops. This leads to falls, loss of confidence and fractured hips. NICE suggest less rigorous targets in those over 80.

Testing blood glucose has largely replaced urine testing

When I was a medical school in the early 1970s, Professor Harry Keen, an expert on diabetes, said that 1% of the population was known to be diabetic and there was another 1% with the disease who did not know about it. Nowadays the figure for known diabetics is just over 6% and rising.60Diabetes Prevalence 2017 Most of this is due to an increase in type 2 diabetes with increasing obesity but type 1 prevalence is also rising and this is far more difficult to explain. A diagnosis of diabetes allows a discussion about management of this disease and its serious implications.

Obesity, high alcohol intake and lack of exercise are all well known risk factors which can only be addressed by the individual taking personal responsibility.

Calculators include multiple risk factors

Coronary heart disease and related stroke risk are multifactorial. As discussed in Cohort or Longitudinal and Epidemiological Studies, doctors now have access to charts for multiple risk factors for CHD and stroke. My experience is that if a patient is told that he has a 20% risk of a heart attack and a 2% risk of a stroke in the next 10 years, he will be much more worried about the 2% risk of a stroke than the 20% risk of a heart attack. Despite all this evidence of risk factors and drugs to modify some and self-discipline to change others, we still need to ask how effective are these interventions.

The first place to look is a Cochrane review. They examined papers from multiple rather than single factor interventions. They took 55 trials of between 6 months and 12 years duration conducted in several countries over the course of four decades. The median duration of follow up was 12 months (with a range of six months to 12 years). They found that multiple risk factor intervention does result in small reductions in risk factors including blood pressure, cholesterol and smoking. Contrary to expectations, multiple risk factor interventions had little or no impact on the risk of coronary heart disease mortality or morbidity. This could be because these small risk factor changes were not maintained in the long term. Alternatively, the small reductions in risk factors may be caused by biases in some of the studies. The methods of attempting behaviour change in the general population are limited and do not appear to be effective.61Multiple risk factor interventions for coronary heart disease

The outcomes for interventions for coronary artery and stroke risk factors are disappointing. The Cochrane reviewers felt that the many disparate techniques to analyse data made their interpretation difficult. Their results do not suggest that interventions are useless but less impressive than we might hope.

The NHS was founded on a false assumption of improving health

Politicians have always been very keen on preventative medicine and screening for CHD risk factors has been an important activity and source of remuneration in general practice since the 1990s. The NHS was said to have been founded at a time of great austerity on the basis that a health service, free at the point of access would so improve the health of the nation that it would save more money than it cost. Politicians have always been very susceptible to wishful thinking rather than evidence. They hope that if heart attacks and strokes are prevented, it will save money.

The trouble is that avoiding heart attacks or cancer in the 60s or early 70s does not mean that we shall live a healthy life for ever or that after many years of healthy and independent living we shall quietly die without troubling the NHS too much. Life expectancy has risen as has years of disability-free life but by not so much. Hence there is more disability in the elderly. As we grow older, we are more likely to trouble the NHS for hip or knee replacements or cataract surgery. We shall need many years of regular medication and as we do not work, we do not contribute to the economy. As we age there is even the risk of the dreaded dementia. A long but relatively health life will still put great demands on the NHS and social care.

Life style is a matter of choice.

Much of the problem seems to be that people are given advice about life style and do not take it. They are prescribed drugs that they do not adhere to. This is a matter of choice. Without testing blood pressure or cholesterol people will not know there is a problem. Life style issues are well known and obvious. Perhaps medical professionals have a greater responsibility to get the message across in ways and words that will be better understood. People have the right to choose an unhealthy life style and to suffer the consequences.

The Galleri Test for Multiple Types of Cancer

A new and potentially exciting prospect that is still in development is called “liquid biopsy”. The Galleri Test could revolutionise cancer screening, but it is seen as a possible addition rather than a replacement for existing programmes. It requires a 10ml blood sample to detect signs of about 50 different cancers before they are clinically apparent.62Novel blood-based early cancer detection: diagnostics in development

In 2021, NHS patients aged 50 to 77 are being recruited in eight areas of England, inviting them to take part in a randomised control trial called the NHS-Galleri study. There will be 140,000 participants who have not had cancer in the past three years.

As a control, only half the samples will be tested immediately, and the other half will be placed in storage so that a comparison can be made between any cancer diagnosis and survival rates. This is to show if early diagnosis by this method really saves lives. All participants will be invited back after 12 months and again at two years to provide further blood samples although they will be advised to continue with other NHS screening appointments. Participants will only know if they are in the test group if potential signs of cancer are spotted in their blood, in which case they will be referred to a hospital for further investigation.

Several years ago, scientists at a DNA sequencing company in San Diego ran a study to see if DNA fragments in pregnant women’s blood may suggest chromosomal abnormalities in their unborn child. Of around 10,000 women tested, about ten had blood samples which showed chromosomal disorders, but the DNA abnormalities suggested cancer. One of the ten was known to have cancer and the other nine had asymptomatic cancer that was undiagnosed at the time.

Cells are shed by tumours which can be detected in blood

The test analyses tiny fragments of cell-free DNA (cfDNA) in the blood. In the presence of cancer, about 0.1% of this cfDNA is shed from tumours and called cell-free circulating tumour DNA (ctDNA). All ctDNA carries information about the kind of cancer that created it. The ctDNA can be analysed for any chemical changes, or DNA methylation patterns, that suggest cancer. The test also indicates what type of cancer it is. As well as this Kings College, London trial, there is also a study in Oxford using the Galleri test. About 6,000 people in England and Wales who have already been referred by their GP for possible cancer have been recruited for the study. They will provide blood samples to see if the tests can help to diagnose any cancers early. Blood samples will be taken from people on a two-week waiting list for a cancer appointment. The aim is to show how many people might have been diagnosed earlier.

In April 2021, an observational study showed that the Galleri test could detect more than 50 types of cancer, with a low false positive rate of less than 1%. The blood test was shown to have accurately detected 29 cancers across 13 types, including breast, colon or rectum, head and neck, liver and bile duct, lung, lymphoid leukaemia, lymphoma, ovary, pancreas, plasma cell neoplasm, prostate, small intestine and Waldenstrom’s macroglobulinemia. Methylation marks on DNA can suggest cancer, but they also vary between tumours and indicate the type of cancer. Participants will be followed for a further 12 months, with final results expected in the first half of 2022.

The Galleri test can help to identify 51 different types of cancer, but the strongest evidence is for identifying lung, ovarian, pancreatic, bladder, oesophageal, stomach, anal, lymphoma, plasma cell, liver and bile duct, head and neck cancers. It will also detect leukaemia, bone cancers, kidney, prostate, gallbladder, vagina, mouth and throat, penis and nasal cavity cancers. It is less effective at identifying breast cancer, but some types of breast cancer such as oestrogen negative tumours were better detected. They are also a type which can be easily missed with regular screening. The best option may be the Galleri test plus mammography.

Not all cancers shed DNA into the bloodstream. Brain cancers are an example. The test will probably be used in addition to routine cancer screening tests.

The rather low sensitivity makes this test an adjunct rather than a replacement for current screening programmes

It would come as no surprise that large and advanced tumours shed more cfDNA than smaller ones. Although the rate of false positives is acceptably low, the rate of false negatives is rather high. Research was published by an American team which recruited 4,077 people of whom 2,823 had cancer and 1,254 did not. Of the 2,823 people with cancer, the test accurately identified their cancers in 51.5% of cases. This is barely over half. The test is more accurate at detecting advanced cancer with 77% of stage three and 90% of stage four tumours detected compared with 16.8% of stage one cancer and 40% of stage two. However, it picked up 67% of the 12 cancers it is able to pinpoint with most accuracy at stages one to three and was impressive in people with myeloma (bone marrow cancer), successfully identifying 72.3% of cancers and a high percentage of stage one cancers.

The initial results of the Kings College trial will be available at the end of 2023. If results are favourable, there is an agreement between the NHS and the company manufacturing the test to roll it out to one million more people in England in 2024 and 2025. The final results of the trial are expected in 2025. If it works well, it is likely to be introduced for the 15 million people aged 50 to 77 on the NHS. It is already available privately in the USA, but not as part of a screening programme. The cost is about £620.

There is also a test called CancerSeek, licensed by a company called Thrive, which has been developed by scientists at Johns Hopkins University. It measures the levels of eight cancer proteins and the presence of cancer gene mutations in a sample of blood. A study of more than 10,000 healthy older women in 2020 found 26 malignancies that had not been detected with mammograms and colonoscopy examinations. Other, more targeted blood tests are also in development, including one from Bluestar Genomics that detects pancreatic cancer in high-risk patients.

Private Screening

Private screening may be driven by commercial rather than evidence

When the NHS offers a service it ascertains that it represents good value and that it is in the patient’s interest. This is why prostate screening has been rejected. However, there are many people who believe that if they pay for something directly they get a better service. Hence there are a number of private companies that offer screening services. We need to ask if they offer good value to the patient or if the services are driven purely for the financial health of the company.

Some screening tests are for risk factors for heart disease and can be provided by your own general practitioner. You will not get a better service by paying privately any more than you get a better influenza vaccine by paying a pharmacist or other provider rather than getting it from the practice nurse. Screening is sometimes referred to as an MOT. However, just as the test on a car does not cover everything and it can still break down in the following week, health checks also cover limited ground and do not provide full certainty. Some tests sound very impressive, such as a full body MRI or CT scan. As the NHS screening website states, “If you have a problem, do not go for screening but go to your doctor.” CT scans give quite a high dose of radiation. One of their major selling points for whole body MRI is screening for aortic aneurysm. However, an ultrasound scan is a better and much cheaper way of doing this. These whole body scans of apparently healthy people throw up far too many false positives. These unexplained, incidental findings that will probably need investigation are called “incidentalomas”. They cause needless anxiety. They may need further investigation that carries its own risk such as an operation. In the end there is probably no disease.

Further investigation is left to the NHS. They pick up the bill and the pieces.

There are private firms that offer prostate cancer screening and they may not be fully open about the limitations of the procedure and why the NHS has rejected it.

Before undertaking any private screening, discuss false positive and false negatives or sensitivity and specificity and get it in writing to peruse it properly. Ask who is responsible for any follow up and how much it may cost. Since 2010 private screening companies have had to be regulated by the Care Quality Commission (CQC) but they should still be viewed with scepticism.

Risk Factors and Diseases

We have examined a number of screening programmes that are offered by the NHS, but by no means all . In pregnancy there is screening for fetal abnormality with an ultrasound scan and screening for some specific conditions such as Down’s syndrome and open neural tube defect which means an open spina bifida or anencephaly when the brain does not develop. At risk groups may be tested for sickle cell disease or thalassaemia. Not all screening is for the whole population.

Risk is chance, not certainty, but even low risk people benefit by reducing risk further

Having discussed screening for early disease, predisposing factors or premalignant change, it is time for a brief look at some risk factors for diseases. Knowledge of this enables risk to be reduced. This is by no means comprehensive. No references are given in this section and there is no indication of the degree of risk for each. Even the order does not necessarily indicate an order of risk. In some cases a risk factor is genetic and whilst we cannot alter our genes, the knowledge of a genetic predisposition should increase the rigour of avoiding other risk factors. With most cancers, the risk rises with increasing age. The same is true for cardiovascular risk.

Cancer of Cervix

  1. Early age of onset of sexual intercourse. The immature cervix seem to be more susceptible to carcinogens.
  2. Multiple partners
  3. HPV infection. Multiple partners increases the risk that one will be a carrier. Barrier contraception would give some protection
  4. Smoking

Breast Cancer

  1. Family history
  2. Overweight or obese
  3. Breast feeding is protective
  4. Long term use of oral contraceptives gives a small increase in risk
  5. HRT for less than 5 years is insignificant but use for 10 or 15 years is much more significant

Prostate Cancer

  1. Family history
  2. Overweight or obese
  3. Race; more common in black men, less common in Asians

Bowel Cancer

  1. Family history, especially certain uncommon conditions
  2. Inflammatory bowel disease, meaning ulcerative colitis or Crohn’s disease
  3. Overweight or obese
  4. Diet, especially inadequate fibre, too much red meat and too much processed food

Type 2 Diabetes

  1. Family history of type 2 diabetes. Type 1 and type 2 are inherited with different genes.
  2. Overweight or obese. The risk rises sharply as BMI rises
  3. Lack of exercise
  4. Smoking


  1. The sex hormones are anabolic, meaning body building. This applies to oestrogens as well as androgens although they are not as potent. Hence risk factors include anorexia nervosa or underweight as well as an early menopause. Men do not normally have such a drop off of hormones but if they do, it puts them at risk
  2. Family history of osteoporosis
  3. Smoking
  4. Excessive alcohol consumption
  5. Weight bearing exercise is protective. This does not include swimming

Gamblers overestimate their chance of winning.
Risk takers, such as smokers, underestimate their chance of getting caught out.
If you lose money you can walk away.
If you lose your life you can not.

Risks of Smoking

  1. Smoking increases the risk of cancers of the larynx, mouth, oesophagus, lung, pancreas, bladder and cervix
  2. It increases the risk of heart attack and stroke and blockage to the arteries to the lower limbs
  3. Lung disease, especially COPD and aggravating other lung conditions
  4. Reduced fertility in male and female
  5. Smoking in pregnancy increases the risk of miscarriage, stillbirth, premature labour, small babies and even at age 7 the children tend to have slow reading ability
  6. Premature aging of arteries, lungs and skin

Risks of Obesity

  1. There are a number of cancers associated with obesity. Cancer Research UK say that it causes 6% of all cancers but I have seen figures as high as 30%. It is said to be the second commonest avoidable cause of cancer, after smoking. As smoking becomes less prevalent and obesity becomes more common, the contribution of obesity as an avoidable factor for cancer rises.
  2. Cancers caused by obesity include breast in post-menopausal women, bowel, body of uterus rather than cervix, oesophagus, pancreas, kidney, liver, upper stomach (gastric cardia), gallbladder, ovary, thyroid, myeloma (a type of blood cancer), and meningioma (a type of brain tumour).
  3. It increases the risk of heart attacks and strokes as well as type 2 diabetes
  4. Osteoarthritis
  5. Sleep apnoea
  6. Hormonal problems including polycystic ovary disease in women and poor fertility in both men and women

Fat is important in the metabolism of the sex hormones. An inadequate amount as in anorexia nervosa leads to low levels of oestrogens and the problems that go with that. Obesity leads to high levels of both male and female sex hormones. This includes polycystic ovary disease in women where high levels of androgens leads to scanty, irregular or absent periods with infertility as well as male pattern hair in the pubic region, face and chest. There can also be male pattern baldness. Obese men have high oestrogens too giving the “man boobs” and even male breast cancer.

Further Resources


  1. Biotopics. TB prevention and control
  2. Wilson JMG, Jungner G. Principles and Practice of Screening for Disease. WHO Chronicle 1968;22(11):473
  3. Papanicolaou GN, Traut HF 1941. The diagnostic value of vaginal smears in carcinoma of the uterus. Arch Pathol Lab Med. 1997 Mar;121(3):211-24 No abstract available.
  4. NHS cervical screening programme.
  5. Chang AR 1990.Carcinoma in situ of the cervix and its malignant potential. A lesson from New Zealand. Cytopathology. 1990;1(6):321-8. Review.
  6. UK Cervical Cancer mortality statistics, Cancer Research UK. 2016
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Site Index

This website is now completed, although I shall continue to do updates. The following list shows the sections or chapters. Just click on the topic in blue to go to that part of the site.

1 Introduction
2 A Very Brief History of Science And Medicine
  Fundamentals of Medical Science
3 Finding Good Medical Advice and Evidence Based Medicine
4 Randomised Controlled Trials
5 Cohort or Longitudinal and Epidemiological Studies
6 Qualitative Research
7 Basic Maths in Medical Research and Decision Making
8 How Good is the Evidence?
9 Ethics in Practice and Research
  Public Health Issues
10 Screening Programmes
11 Fake News and Vaccine Scares
12 Electronic Cigarettes (E-Cigarettes)
13 Motor Vehicle Emissions, Air Pollution and Health
14 COVID-19. What You Need to Know
15 Who is at Risk from COVID-19
16 What we Must Learn from the COVID-19 Pandemic
17 Basics of Nutrition
18 Exercise, Obesity and Diets for Weight Loss
19 Diets and Nutrition for Health and Fitness
20 Supplements
  Complementary and Alternative Medicine
21 Introduction to Alternative Healthcare
22 Homeopathy
23 Acupuncture
24 Manipulation of the Spine
25 Reflexology
26 Herbal Remedies
27 Other Natural Products
28 Chelation Therapy
29 Hypnosis
30 Other Modalities of Complementary and Alternative Medicine
  Some Controversial Diseases
31 Fibromyalgia
32 Chronic Fatigue Syndrome (CFS) or Myalgic Encephalitis (ME)
33 Systemic Candidiasis and Leaky Gut Syndrome
34 Mobile Phones, Masts, Wi-Fi and Electro-sensitivity
  The Environment
35 Global Warming and Climate Change
36 Alternative Energy
  Some Final Thoughts
37 Still Searching for the Age of Reason