Cancer screening: Evidence and practice in Europe 2008

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Abstract

We examine the theoretical basis of screening, followed by an evaluation of screening initiatives from a population health perspective and a discussion of the organisation of mass screening programmes. Evidence for the effectiveness of screening by primary site from both randomised trials and evaluation of service screening is summarised and the existing cancer screening programmes in the European Union are described. Sufficient evidence from several randomised trials to demonstrate mortality reduction exists for breast cancer and colorectal cancer screening. At least one trial has shown efficacy with a mortality end-point in screening for hepatocellular carcinoma and oral cancer. Randomised trials have demonstrated a lack of mortality effect in lung cancer screening based on chest X-ray and sputum cytology. Despite the lack of randomised trials, population screening for cervical cancer with cytological smears has been convincingly shown to reduce cervical cancer incidence and mortality.

Introduction

Screening can be defined as the application of a simple test to identify early, asymptomatic disease. The primary purpose of cancer screening is to reduce cancer mortality. In addition, screening has other important consequences, including the use of economic resources (health expenditure) and potential quality of life effects, whether positive or negative.

Since cancer is always a potentially lethal disease, the primary goal of cancer screening (and subsequent treatment) is extending lives. The ultimate effectiveness of cancer screening is measured in terms of mortality reduction and this aim motivates initiation, management and evaluation of cancer screening as a public health policy.

Cancer screening requires a detectable pre-clinical phase of the target disease, during which the disease can be treated so that its progression to overt disease is stopped.1 The duration of the detectable pre-clinical phase is referred to as the ‘sojourn time’.2 Its duration varies, depending on the natural course of the disease, the screening test and diagnostic assessment.

Ideally, a screening programme should reduce the burden of disease in terms of death and morbidity and/or improve the quality of life. The prognosis of screen-detected cancer cases should be better than for those detected clinically, due to earlier detection and treatment. Yet, screening always has also adverse effects. Screen-detected cases often include indolent lesions, some of which would not progress even if untreated.3, 4, 5 Such lesions may fulfil the histological criteria for malignancy, but nevertheless behave clinically in an indolent fashion. Any screening programme will detect such abnormalities; therefore one of the adverse effects of screening is over-diagnosis and over-treatment, i.e. detection and management of disease that would not have been diagnosed during the lifetime of the subject in the absence of screening.

The natural history of disease and treatment outcomes define the limits of screening. If a disease is fully curable after detection at a symptomatic phase, there is no need for screening. Screening should not be applied to diseases for which no effective treatment is available.

Section snippets

Evaluating the effectiveness of screening

A screening programme should have high sensitivity and specificity. Sensitivity is the capacity to detect cases in the pre-clinical detectable phase amongst those screened.6 Sensitivity sets the limits for achievable effectiveness, since, reduction in disease burden is achieved only through screen-detected disease. Specificity is the ability to correctly identify subjects without the disease. Specificity is important because it is essential to minimise the number of ‘false positives’ or healthy

Organising a screening programme

Screening is a chain of activities that starts with defining the target population and extends to the treatment and follow-up of the screen-detected patients. A screening programme consists of several interlinked activities. Various cancer screening programmes may consist of different components (Table 1).

Screening can be opportunistic (spontaneous and unorganised) or organised (mass screening and screening programmes). The major differences lie in the level of organisation and planning and the

Effectiveness of cervical cancer screening

The objective of cervical cancer screening is to reduce both cervical cancer incidence and mortality. A successful screening programme detects early, pre-invasive lesions during the pre-clinical detectable phase and is able to reduce deaths by preventing the occurrence of invasive cancer. Diagnostic assessment requires colposcopy examination, with the evaluation of morphological features of the cervix as well as histological assessment.

The value of the Papanicolaou (Pap) smear in reducing the

Screening for breast cancer

In breast cancer screening, the primary target lesion is early invasive cancer, but ductal carcinoma in situ is also detected with a frequency that is up to a fifth of that for invasive cancer.

Mammography involves radiological imaging of the breast with one or two views, read by one or two radiologists. A screen-positive finding is a lesion that is suspicious for breast cancer. Two views are likely to increase the sensitivity by approximately 20%, with the greatest incremental benefit for the

Effectiveness of colorectal cancer screening

Several screening methods are available for colorectal cancer screening, including faecal occult blood testing, sigmoidoscopy, colonoscopy and double-contrast barium enema.

Faecal occult blood (FOB) testing is based on the detection of haemoglobin in stools using guaiac-impregnated patches, where an oxidative reaction results in a colour change that is detectable on inspection. The most commonly used test, Hemoccult II®, is not specific for human blood and so may yield false positives in people

Screening for prostate cancer

Screening for prostate cancer is mainly based on serum prostate-specific antigen (PSA), which is a serine protease (enzyme) secreted by the prostate gland. It is usually found in low concentrations in serum, with levels increased by prostate diseases such as benign prostatic hyperplasia, prostatitis or prostate cancer.

Two large randomised trials are being carried out, one in Europe and the other in the USA. The European Randomised trial of Screening for Prostate Cancer (ERSPC, //www.erspc.org/

Lung cancer

The target lesion for lung cancer screening is early, resectable (stage 1) carcinoma. Conclusive diagnosis of early lung cancer is based on biopsy, usually obtained by bronchoscopy for central tumours and excision biopsy for peripheral tumours.

The available screening protocols for lung cancer include screening with chest X-rays, with or without sputum cytology, and spiral low-dose CT. Several trials have been conducted to assess the mortality effect of chest X-rays and sputum cytology compared

Conclusion

In summary, establishing the benefits of screening requires evidence on mortality effects from large randomised trials. A summary of the current evidence for cancer screening is provided in Table 5. Screening tests are available for many primary cancer sites, but either their effectiveness has not been evaluated adequately or a lack of effectiveness has been demonstrated. Even when efficacy trials (typically conducted in specialist centres with volunteer subjects) have been successful, mass

Conflict of interest statement

None declared.

Acknowledgements

The article is partly based on ’Cancer Screening’ chapter in Encyclopedia of Public Health (Elsevier 2008) by Matti Hakama and Anssi Auvinen. We thank prof. Jan-Willem Coebergh for comments and suggestions.

References (62)

  • F.E. Alexander et al.

    4 years of follow-up from the Edinburgh randomised trial of breast-cancer screening

    Lancet

    (1999)
  • L. Nyström et al.

    Long-term effects of mammography screening: updated overview of the Swedish randomised trials

    Lancet

    (2002)
  • S.M. Moss et al.

    Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years’ follow-up

    Lancet

    (2006)
  • R. Sankaranarayanan et al.

    Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial

    Lancet

    (2005)
  • M.R. Melamed et al.

    Screening for early lung cancer

    Results of the Memorial Sloan-Kettering study in New York. Chest

    (1984)
  • H.E. Karim-Kos et al.

    Recent trends of cancer in Europe: A combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s

    Eur J cancer

    (2008)
  • W. Zatoński et al.

    Closing the gap: Cancer in Central and Eastern Europe (CEE)

    Eur J Cancer

    (2008)
  • P. Cole et al.

    Basic issues in cancer screening

  • N.E. Day et al.

    Simplified models for screening: estimation procedures from mass screening programmes

    Biometrics

    (1984)
  • Breast Cancer Screening. IARC handbooks of cancer prevention, vol. 7. Lyon: IARC Press;...
  • Cervix Cancer Screening. IARC handbooks of cancer prevention, vol. 10. Lyon: IARC Press;...
  • J. Hugosson et al.

    Would prostate cancer detected by screening with prostate specific antigen develop into clinical cancer if left undiagnosed

    BJU Int

    (2000)
  • M. Hakama et al.

    Sensitivity in cancer screening

    J Med Screen

    (2007)
  • M. Feinleib et al.

    Some pitfalls in the evaluation of screening programs

    Arch Environ Health

    (1969)
  • G.B. Hutchison et al.

    Lead time gained by diagnostic screening for breast cancer

    J Natl Cancer Inst

    (1968)
  • J. Cuzick et al.

    Adjusting for non-compliance and contamination in randomised clinical trials

    Stat Med

    (1997)
  • O. Jørgensen et al.

    A randomised study on screening for colorectal cancer using faecal occult blood testing: results after 13 years and seven biennial screening rounds

    Gut

    (2002)
  • M. Hakama

    Selective screening by risk groups

  • Screening for cancer of the uterine cervix. Geneva: WHO;...
  • A. Anttila et al.

    Cervical cancer screening programmes and policies in 18 European countries

    Br J Cancer

    (2004)
  • J.F. Nygard et al.

    The cervical cancer screening programme in Norway, 1992–2000: changes in Pap smear coverage and incidence of cervical cancer

    J Med Screen

    (2002)
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