Introduction
Screening as a means to detect disease early is an established public health function throughout Europe. However, it is not without controversy. In theory, the early detection of disease, or a marker of future disease, makes perfect sense. Detection will make it possible to intervene at an early stage and prevent the development or progression of the disease. However, in reality, the situation is much more complicated and there are many screening programmes that either fail to meet their potential or, worse, are completely ineffective or even harmful.
There is a crucial distinction between organized screening (based on a defined target population, central organization and planning, systematic monitoring of uptake by different groups within the population, evidence- based screening intervals, and quality assurance systems) and opportunistic screening (offered spontaneously by healthcare providers when patients use health services or at the request of patients) (Holland and Stewart 2005; Hakama, Coleman et al.
2008). Organized screening is almost always more efficient, makes better use of available resources, and is less likely to result in harm.
In this chapter, we focus mainly on screening programmes for cancer but, before looking at them in detail, it should be noted that there are several other categories of screening programmes. The first category includes those undertaken to detect severe foetal abnormalities, such as neural tube defects or chromosomal anomalies such as Down’s syndrome. Detection of such a severe anomaly will allow the mother to be counselled and offered termination of pregnancy. Other screening tests are offered to mothers at high risk of specific disorders because of their family history. The most recent European survey of antenatal screening practices, undertaken in 18 countries in 2004, reported that 10 had policies or recommendations in place to screen for Down’s syndrome (Table 9.1) and 14 for structural abnormalities (Boyd, Devigan et al. 2008).
However, policies vary, both with regard to the methods used and the criteria for identifying those at highest risk. Thus, the incidence of Down’s syndrome
increases with maternal age but there is considerable variation in the age at which amniocentesis or chorionic villous sampling (CVS) is offered. A key consideration is the variation in access to termination of pregnancy within Europe. At the time of writing, there is a virtual ban on termination in Ireland and Malta, requiring those women seeking termination to travel abroad, while it is heavily restricted in Poland.
A second category of screening programmes is administered to newborn babies. These are largely uncontroversial and can be done cheaply and easily using a spot of blood taken at birth. Although the conditions that they are seeking to detect are rare, they have severe consequences if detected late and consequently go untreated. In each case, there is a treatment available that can significantly modify the course of the disease. The range of disorders that can be screened for has increased rapidly with the introduction of new technologies, with some countries offering tests for up to 20 abnormalities. The situation in Europe in 2007 has been reviewed in a recent survey (Bodamer, Hoffmann et al. 2007) but is changing rapidly. Examples of the more common abnormalities sought include phenylketonuria, which will lead to serious and irreversible mental disorders unless the affected child is given a special diet, congenital hypothyroidism, which again leads to severe learning Table 9.1 Policies on screening for Down’s syndrome in 18 European countries in 2004 Country National screening programme
Belgium Yes 36 (charged if <36)
Croatia No 35
Denmark Yes Not offered primarily on basis
of maternal age England and
Wales
Yes Not offered primarily on basis
of maternal age
Switzerland Yes Not offered primarily on basis
of maternal age Source: Boyd, Devigan et al. (2008)
Screening 155 difficulties unless treated with thyroid hormone, a simple oral preparation, and medium- chain acyl- CoA dehydrogenase deficiency (MCADD), again treated with a special diet. In some European countries, the newborn screening regime also includes tests for disorders that, while there is no single effective treatment, it is possible to address with a range of measures that will slow progression of the disease or reduce its consequences – these are cystic fibrosis and sickle cell disease. The latter is an example of a condition for which it is necessary to consider the background prevalence. It occurs almost entirely in persons of Afro- Caribbean origin and thus screening will be most important in countries where this ethnic group is present in significant numbers.
A third category of screening programmes is for infectious disease, particularly tuberculosis (TB), although antenatal screening for syphilis is also widespread. While some countries limit screening for TB to contacts of sputum smear- positive pulmonary TB, others screen people who are HIV- positive, prisoners, and hospital contacts of inpatients (Bothamley, Ditiu et al.
2008). There are also some high- prevalence countries in the eastern part of the WHO European Region, such as Belarus and Ukraine, that still rely on diagnosis through mass screening of the population by X- ray (Atun and Olynik 2008; Richardson, Boerma et al. 2008). Of 50 European countries covered in a survey in 2006, 28 countries screened immigrants for TB (Bothamley, Ditiu et al. 2008). However, the individual and public health benefit of this practice, as well as the ethical issues involved, are highly contested (Wörmann and Krämer 2011).
A fourth category of screening programmes is related to risk factors for non- communicable diseases and their risk factors, such as hypertension, overweight and obesity, lack of physical activity, tobacco and alcohol consumption, high cholesterol and blood glucose levels, and salt in urine. European initiatives, aimed at improving the prevention of cardiovascular disease, include guidelines for clinical practice (Perk, De Backer et al. 2012). These actions are in line with the 2008–2013 Action Plan for the Global Strategy for the Prevention and Control of Non- communicable Diseases, which recommends programmes for the early detection of and screening for hypertension, diabetes, and cardiovascular risk (WHO 2008).
This chapter explores a final category of screening programmes, those aiming to detect cancer in its early stages. We begin by reviewing the established criteria for implementing a screening programme. We then review the evidence for screening for selected conditions, including some of the current controversies.
This is followed by a brief overview of screening practices across Europe.
Finally, we examine the public health role in the organization and management of screening programmes.
When is a screening programme justified?
Basic criteria for evaluating screening programmes were set out in a 1968 report prepared for the World Health Organization (WHO) (Box 9.1).
Box 9.1 Basic criteria for evaluating screening programmes 1. The condition should be an important health problem.
2. There should be a treatment for the condition.
3. Facilities for diagnosis and treatment should be available.
4. There should be a latent stage of the disease.
5. There should be a test or examination for the condition.
6. The test should be acceptable to the population.
7. The natural history of the disease should be adequately understood.
8. There should be an agreed policy on whom to treat.
9. The total cost of finding a case should be economically balanced in relation to medical expenditure as a whole.
10. Case- finding should be a continuous process, not just a “once and for all” project.
Source: Wilson and Jungner (1968)
It is apparent from studying these criteria that it may be justifiable to set up a screening programme for a given condition in some settings but not in others. It makes little sense to screen for a condition that is extremely rare because this will involve subjecting perhaps tens of thousands of people to an examination just to detect one case. However, the incidence of conditions for which one might wish to screen may vary between populations. Thus, it may be appropriate to screen for a particular form of cancer where it is common but not where it is rare. This may also change over time. The increasingly common practice of immunizing adolescent girls against human papilloma virus will in time make cervical cancer extremely uncommon, so that existing screening programmes for this condition might become superfluous. However, the importance of a condition is not judged simply by its frequency. A further consideration is its impact on the individual concerned. To be important, it should be life threatening or at least pose a risk of significant impairment. As a consequence, screening programmes have focused largely on cancers and inherited errors of metabolism and foetal anomalies. There are increasing calls to screen for cardiovascular disease and associated risk factors, but some argue that the necessary resources would be better spent on population- level initiatives to reduce exposure to these risk factors in the first place (McCartney 2012).
The second and third criteria are equally self- evident but have often been ignored in practice. During the 1980s, a number of then communist countries in central and eastern Europe implemented radiological screening for lung cancer, using equipment that was otherwise under- utilized for the diagnosis of TB. Unfortunately, there was little that could be offered in treatment to those identified as having cancer. The fourth criterion requires that there be a stage in the disease process when treatment can make a difference. As in the example of lung cancer screening, by the time the tumour is detectable, it is likely to no longer be operable. The fifth and sixth criteria relate to the existence of a test for the condition that is feasible and acceptable. It would not make sense to
Screening 157 screen people by means of invasive surgery or exposure to excessive amounts of radiation. In practice, however, these criteria are not always adhered to, leading to suboptimal or even adverse outcomes.
The evidence for cancer screening programmes
The Council of the European Union, after reviewing the evidence base on population- based screening programmes for cancer, concluded that there is justification to screen for cancer of the cervix, breast, and colon, provided there are appropriate quality assurance systems (Council of the European Union 2003). These recommendations were endorsed by the WHO Regional Committee for Europe for the 53 member states of the WHO European Region (WHO 2011). These three types of cancer (cervix, breast, and colon) are among the most common and deadly cancers, accounting for almost 20% of cancer deaths in the WHO European Region.
The earliest cancer screening programmes aimed to prevent the development of cervical cancer. It has long been recognized that changes in the cells of the cervix can be identified long before the development of invasive cancer, with a typical interval of 10–12 years (Gustafsson and Adami 1989; van Oortmarssen and Habbema 1991). Initially based on the detection of cancer cells, screening was extended in some countries to detect human papilloma virus, the cause of cervical cancer. Data from observational studies indicate that well- organized cervical screening programmes can reduce mortality from cervical cancer by 80% or more (International Agency for Research on Cancer 2005).
The evidence for the effectiveness of breast cancer screening is more controversial. Although, unlike screening for cervical cancer, breast cancer screening has been subject to a number of randomized controlled trials with long- term follow-up, these have been of low or moderate quality. Data from these trials suggest that biannual mammography (X- ray of the breast) screening programmes in women aged between 50 and 69 years can decrease mortality by approximately 25%. Observational data of routine practice suggest that this may be an overestimate of what can be achieved and some studies even dispute the benefits of screening. A study comparing breast cancer mortality in six European countries found that screening was unlikely to have played a role in mortality reductions (Autier, Boniol et al. 2011). Similar findings in the United States led the Preventive Services Task Force (an independent panel of experts in primary care and prevention) in 2009 to recommend the discontinuation of routine breast cancer screening in women younger than 50 and the reduction of screening intervals from one to two years for those aged 50–74. However, this met with resistance from groups with vested interests in mammography, leading to the so- called “mammography war” (Bleyer 2011). However, a major weakness of these more critical studies is that they have not used longitudinal individual data that would make it possible to distinguish those women who were screened from those who were not. Studies using such longitudinal individual data for Europe have found reductions in mortality of 25–31% for women invited for screening and 38–42% for women screened (Broeders, Moss et al. 2012).
It is now recognized that mammography will identify a significant number of lesions that are either not malignant or will progress very slowly if at all.
Concerns have therefore been voiced about the effectiveness of mammography and the consequences of over- diagnosis (Gotzsche, Jorgensen et al. 2012). A study of breast cancer incidence in the United States between 1976 and 2008 found that the mammography programme there was associated with a large increase in the detection of early- stage breast cancer, but only a marginal reduction of late- stage breast cancer, suggesting substantial over- diagnosis and only a small effect of screening on breast cancer mortality (Bleyer and Welch 2012). A recent review undertaken in the United Kingdom concluded that the existing mammography programme should be continued, as it will reduce mortality, although at the cost of a number of women being treated unnecessarily (Independent UK Panel on Breast Cancer Screening 2012).
The third cancer that is the subject of screening programmes in a number of European countries is colorectal cancer, but programmes have only been implemented relatively recently (von Karsa, Anttila et al. 2008). Randomized controlled trials have shown that biannual screening using the faecal occult blood test among those aged 50–74 can reduce mortality by about 16% (Hewitson, Glasziou et al. 2007). This is somewhat smaller than the reduction seen with screening for cervical and breast cancer and there is considerable debate about whether screening programmes for colorectal cancer are cost- effective.
Advances in technology may make it possible to screen for cancers or other diseases for which there is currently no effective means for early diagnosis or treatment. One cancer that is currently attracting attention in this regard is that of the ovary. Another, much more controversial example that has been advocated to be included in future screening programmes is prostate cancer, identified through prostate- specific antigens (PSAs). The European Randomized Study of Screening for Prostate Cancer, involving 162,388 patients in eight European countries, found a reduction in prostate cancer mortality of 20% after 9 years. However, it is necessary to treat almost 50 men with an elevated PSA level to save one life, while many of those treated will be left with potentially severe side- effects. For this reason, there are significant concerns that screening will lead to over- diagnosis and over- treatment (Schröder 2012).
Cancer screening practices in Europe
As mentioned above, the EU and the WHO Regional Office for Europe recommend organized, population- based screening programmes for cervical, breast, and colorectal cancer (Council of the European Union 2003; WHO 2011).
Yet, there is still considerable variation across countries in how far they have followed these recommendations. By 2007, 22 of the 27 EU countries were running population- based screening programmes for breast cancer, 15 for cervical cancer and only 12 for colorectal cancer (von Karsa, Anttila et al. 2008).
Few countries in Europe have a single national body to review screening practice and policy, and population registers for call and recall and follow- up of patients are also comparatively rare (Holland, Stewart et al. 2006). Although there are exceptions, such as Slovenia, progress has been in general slowest in
Screening 159 countries in central and eastern Europe, in particular the countries of the former Soviet Union, where early detection and prevention of non- communicable disease was virtually lacking in the Soviet era and is still under- developed (Maier and Martin- Moreno 2011). Most countries in south- eastern Europe have also very little systematic screening for cancers (WHO 2009), but are slowly catching up. Croatia, for example, introduced organized, population- based screening programmes for breast cancer in 2006, colorectal cancer in 2008, and cervical cancer in 2012.
In addition to differences between countries, screening practices also vary within countries, in particular where health service provision and thus screening is devolved to regional or local governments (Holland, Stewart et al. 2006), such as in Spain (García- Armesto, Abadía- Taira et al. 2010). In Belgium, the availability of screening programmes for certain types of cancer differs among the country’s three communities (Gerkens and Merkur 2010). In Denmark, too, access to screening programmes varies and organized breast cancer screening only takes place in some parts of the country (Strandberg- Larsen, Nielsen et al. 2007). Italy is another country with very pronounced regional differences, leading to cross- regional patient flows. National screening programmes for breast, cervical, and colorectal cancer were only established in 2004 and coverage differs considerably across regions (Lo Scalzo, Donatini et al. 2009).
Cervical cancer screening programmes
Although there is widespread consensus about the technical aspects of undertaking screening for cervical cancer, including the optimal ways of obtaining a high- quality sample and examining it, countries differ widely in the organization of cervical cancer screening programmes. Major differences relate to whether screening programmes have been set up or not, whether they are systematic or opportunistic, and what percentage of the target population they reach (Table 9.2).
Organized, population- based screening takes place in the Czech Republic, Denmark, Estonia, Finland, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, the Netherlands, Norway, Poland, Slovenia, Sweden, and the United Kingdom (Table 9.2). In most cases, it includes the maintenance of registers of women at risk, covering all women living in a given area within a specified age range who are not otherwise ineligible by, for example, having had a hysterectomy, as well as integrated systems to issue regular invitations and to ensure that any abnormalities are followed up. The interval between successive examinations is typically 3–5 years, depending on the woman’s age. The entire system is subject to regular quality assurance. Organized, population- based screening can have a significant impact on disease- specific mortality levels. In Finland, where organized cervical cancer screening was established in the 1960s, age- standardized mortality rates have declined by approximately 80% (Anttila and Nieminen 2007).
In contrast, in some other countries in Europe, such as Armenia, Austria, Belgium, Bosnia and Herzegovina, and Germany, screening is opportunistic.
Women are offered examinations, typically when they attend their physician or
Table 9.2Cervical cancer screening practices in selected European countries, 2012 Type of screeningGeographical scope of programmeAge range (years)Screening interval (years) AlbaniaNo dataNo dataNo dataNo data ArmeniaOpportunisticNational30–603 AustriaOpportunisticNational18–not specified1 AzerbaijanNo programme——— BelarusOpportunisticNational18–no limit1 BelgiumOpportunisticNational25–643 Bosnia and HerzegovinaOpportunisticNational20–no limit1 (extended to 3 years after 3 consecutive negative smears) BulgariaOpportunisticNational30–593 CroatiaOpportunisticNational25–643 CyprusNo programme——— Czech RepublicOrganizedNational25–60 DenmarkOrganizedNational23–653 in age 23–50 (5 for 50+) EstoniaOrganizedNational30–593 FinlandOrganizedNational(25) 30–60 (65)5 FranceOpportunistic, organized in 5 regionsNational20 (25)–not specified3 Former Yugoslav Republic of MacedoniaOpportunisticNational30–553 GeorgiaOpportunistic, organized in 1 regionNational25–603 GermanyOpportunisticNational20–not specified1 GreeceOpportunisticNational20–not specified1 HungaryOrganizedNational25–653 IcelandOrganizedNational20–692 up to age 39, 4 years afterwards IrelandOrganizedRegional, national planned25–653 in age 25–44, 5 years afterwards ItalyOrganizedNational25–643
LatviaOrganizedNational25–70342% LithuaniaOrganizedNational25–6039–17% (39%) LuxembourgOpportunisticNational15–not specified1No data MaltaNo programme———— MoldovaOpportunisticNational20–no limit2No data MontenegroOpportunisticNational25–643No data NetherlandsOrganizedNational30–60577% NorwayOrganizedNational25–69375% PolandOrganizedNational25–59323–27% PortugalOrganized in 3 regionsNational25–64358% RomaniaOpportunistic, organized in one pilot regionNational25–64318% (10% in pilot region) Russian FederationOpportunisticNational18–no limit115–20% SerbiaOpportunistic (organized in process of implementation)
National25–65 (69)320% SlovakiaOpportunisticNational23–64317–20% SloveniaOrganizedNational20–64370–74% SpainOpportunistic, organized in regionsRegional30–653No data SwedenOrganizedNational23–60373% SwitzerlandOpportunisticNational20–no limit380% (age 22–44), 65% (age 45–64) TurkeyOpportunisticNational18–no limit1No data UkraineOpportunisticNational18–651No data United KingdomOrganizedNational(20) 25–60 (64)374% Source: Adapted from Kesic, Poljak et al. (2012)
gynaecologist for other purposes. As a consequence, they may undergo many more examinations in their lifetime than in those countries with organized screening programmes. In some cases, they may undergo examinations as frequently as every 6 months. In Germany, a woman could have up to 50 smears in her lifetime, while in Finland she is unlikely to have more than seven. However, the age- standardized death rate from cervical cancer in the former is almost twice that in the latter (WHO 2012). Furthermore, because this approach to screening is opportunistic, it will often miss those at greatest risk.
Cervical cancer is much more common in women of lower social class, but they are least likely to attend their physicians for other purposes.
While opportunistic screening for cervical cancer has reached coverage rates of 70–71% and resulted in a reduction of cervical cancer mortality in countries
While opportunistic screening for cervical cancer has reached coverage rates of 70–71% and resulted in a reduction of cervical cancer mortality in countries