Cancer Prevention and Screening E-Book
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Winner of the Council Chair's Choice Award at the 2019 British Medical Association Awards. Cancer Prevention and Screening offers physicians and all clinical healthcare professionals a comprehensive, useful source of the latest information on cancer screening and prevention with both a global and a multidisciplinary perspective. * Includes background information on epidemiology, cancer prevention, and cancer screening, for quick reference * Offers the latest information for clinical application of the most recent techniques in prevention and screening of all major and many lesser cancer types * Emphasises the importance of multidisciplinary teamwork in cancer screening * Highlights frequent dilemmas and difficulties encountered during cancer screening * Provides clear-cut clinical strategies for optimal patient education, communication, and compliance with cancer prevention techniques
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Table of Contents
Cover
Foreword
CHAPTER 1: Global perspectives surrounding cancer prevention and screening
Principles of cancer control strategy
Magnitude of the problem: Proportion of cancer globally attributable to preventable causes
Primary prevention strategies globally
Screening
Early diagnosis
Conclusion
References
CHAPTER 2: Public health perspectives surrounding cancer prevention and screening: The Ontario edition
Context: Health care in Canada
What is happening at the federal level?
What is happening at the provincial level? Cancer Care Ontario
Cancer prevention in Ontario led by CCO
CCO’s provincial cancer screening programmes
Conclusion
References
CHAPTER 3: Cancer screening: A general perspective
On the nature of screening
Assessing a screening test
Assessing benefit from a screening test
The order of evidence of benefit
The population screened
The magnitude of screening benefit
Screening in practice
Conclusion
References
CHAPTER 4: The balance of cancer screening risks and benefits
Cervical screening
Breast screening
Colorectal cancer screening
Prostate cancer screening
Psychological harms of screening
Informed decision‐making
Conclusion
References
CHAPTER 5: Cancer screening issues in black and ethnic minority populations
Conclusion
References
CHAPTER 6: Public awareness of cancer screening
Awareness of cancer screening
Beliefs relevant to cancer screening
Intention and action
Conclusion
References
CHAPTER 7: Public understanding of cancer prevention
Public understanding of prevention
What can we do to improve understanding?
Conclusion
References
CHAPTER 8: Cervical cancer screening: An exemplar of a population screening programme, and cervical cancer prevention
How do we screen for cervical precancer?
Molecular‐based cervical screening technologies
Consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors
Risk assessment to guide cervical screening strategies
Male Circumcision and Cervical Cancer
Conclusions
References
CHAPTER 9: Prevention of and screening for anal cancer
Primary prevention
Secondary prevention
Conclusion
Acknowledgements
References
CHAPTER 10: The prevention of breast cancer
Estimation of risk of breast cancer
Clinical breast cancer prevention
Lifestyle change
Risk‐reducing surgery
Conclusion
References
CHAPTER 11: Breast cancer: Population and targeted screening
Evidence for the benefit of breast cancer screening
Balance of benefits and harms
Implementation of mammography screening in different countries
New technologies in breast cancer screening
Conclusion
References
CHAPTER 12: Prostate cancer prevention
Rationale for prostate cancer prevention
Risk factors
Chemoprevention
Dietary supplements
Prostate cancer prevention clinical trials
Conclusion
References
CHAPTER 13: Population screening for prostate cancer
Screening
Future developments
Conclusion
References
CHAPTER 14: Colon cancer prevention
Genetic architecture of colorectal cancer
Prevention strategies for colorectal cancer
Personalized chemoprevention with aspirin
Prescribing aspirin to the general and high‐risk populations
Future work and novel therapies
Conclusion
References
CHAPTER 15: Colon cancer screening
Rationale for CRC screening
Stool blood testing
Sigmoidoscopy
Colonoscopy
Post‐polypectomy surveillance
Screening guidelines
References
CHAPTER 16: Lung cancer prevention
The occurrence of lung cancer
The causes of lung cancer and opportunities for prevention
Chemoprevention of lung cancer
The burden of avoidable lung cancer
Conclusion
References
CHAPTER 17: Lung cancer screening
Screening for lung cancer: Early approaches
Randomized controlled trials
False‐positive examinations: A serious challenge
Radiation risk
Recommendations for screening
Risk‐based models to better select screening populations
Screening in never smokers
Cost‐effectiveness
Critical interface with smoking cessation programmes
Implementation of screening programmes
Conclusion
References
CHAPTER 18: Mesothelioma: Screening in the modern age
Role of screening
Identifying the at‐risk population
Screening methodologies
Conclusion
References
CHAPTER 19: Skin cancer prevention and screening
Causes of skin cancer
Incidence
Cost of skin cancer
Controversies in prevention
Population screening for melanoma
References
CHAPTER 20: Screening and prevention of oral cancer
Screening
Role of primary care clinicians and health workers in screening
Role of mouth self‐examination.
Tests for screening (see Table 20.2)
Prevention of oral cancer
Chemoprevention of oral cancer
Conclusion
References
CHAPTER 21: Oesophageal cancer
Global perspective
Oesophageal adenocarcinoma
Risk factors
Prevention and screening in EAC
Future perspectives
Conclusion
References
CHAPTER 22: Hepatocellular carcinoma: Prevention and screening
Definition and epidemiology
Liver cirrhosis and HCC
Risk factors for HCC: Specific liver diseases
Risk factors for HCC: General risk factors
Interventions to reduce risk
Screening for HCC
Screening methodology
Effectiveness of screening
Cost‐effectiveness
Conclusion
References
CHAPTER 23: Ovarian cancer prevention and screening
Lifetime risk of ovarian cancer
Risk factors
Risk‐prediction models
Prevention
Screening for ovarian cancer
Symptom awareness
Conclusion
References
CHAPTER 24: Screening for testicular cancer
Approaches to screening
Identifying men at high risk
Screening for testicular cancer: The challenges
Screening for testicular cancer: Future directions
Conclusion
References
CHAPTER 25: Issues in paediatric cancers
Prevention
Screening
Ethics of genetic testing
Screening: Future directions
Late effects of treatment
Conclusion
References
CHAPTER 26: Obesity and dietary approaches to cancer prevention
Assessment of the evidence
Excess body weight (elevated body mass index) and cancer risk
Macronutrients and cancer risk
Alcohol and other drinks
Micronutrients and cancer risk
Dietary patterns
Cancer prevention through weight control and dietary modification
References
CHAPTER 27: Risk profiling for cancer prevention and screening – lessons for the future
Genetic predisposition to cancer: The models
Distribution of genetic risk in a population
Identification of those at risk of cancer due to a genetic predisposition
Technical aspects
Risk profiling models and stratification effects on the screening paradigm
Conclusion
References
CHAPTER 28: Cancer prevention and screening: Advances to carry forward
References
Index
End User License Agreement
List of Tables
Chapter 03
Table 3.1 Positive predictive value.
Table 3.2 Positive predictive value given varying sensitivity, specificity, and prevalence.
Table 3.3 Positive predictive value given varying sensitivity, specificity, and lower prevalence.
Chapter 08
Table 8.1 How to improve different components of a successful screening programme.
Chapter 09
Table 9.1 Relative risk and incidence of anal cancer described in the general population and in various subgroups of the population.
Chapter 10
Table 10.1 Comparison of the effectiveness of models to predict the breast cancers which occurred during follow up of 1900 women in the Genesis Breast Cancer Risk and Prevention Clinic in Manchester. Comparison is made of expected and observed cancers. (Gareth Evans personal communication).
Table 10.2 Comparison of the uptake of tamoxifen for chemoprevention in the Manchester study (Donnelly et al) with most other reported studies in the literature.
Chapter 11
Table 11.1 Characteristics of breast cancer screening programmes in the European Union.
Chapter 12
Table 12.1 US National Cancer Institute–sponsored prostate cancer prevention trials.
Chapter 13
Table 13.1 Requirements of a screening programme.
Table 13.2 Effects of prostate cancer (PCa) screening.
Chapter 14
Table 14.1 Association between environment and lifestyle risk factors and colorectal cancer risk.
Table 14.2 Genes with predisposing mutations in familial colorectal cancer syndromes.
Table 14.3 Consensus molecular subtypes of colorectal cancer based on gene expression profiling.
Chapter 16
Table 16.1 Age‐adjusted SEER incidence and US mortality rates for lung cancer by race/ethnicity and sex, 2007–2011.
Table 16.2 Lung cancer deaths attributable to risk factors, USA, 1990 and 2010.
Table 16.3 Lung cancer deaths attributable to specific risk factors, by global, developed, and developing regions, 2010.
Chapter 17
Table 17.1 Summary of European randomized low‐dose computed tomography (LDCT) lung cancer screening trials.
Table 17.2 Selection criteria for lung cancer screening: Comparison of PLCO
m2012
, NLST, and USPSTF.
Chapter 18
Table 18.1 Studies investigating the diagnostic accuracy of SRMP in malignant pleural mesothelioma.
Table 18.2 Specificity and sensitivity of different biomarkers.
Chapter 20
Table 20.1 Guidelines for oral cancer screening.
Table 20.2 Sensitivity and specificity of various screening tests for oral cancer.
Chapter 23
Table 23.1 Risk factors for ovarian cancer (OC).
Chapter 25
Table 25.1 Surveillance strategy for individuals with germline TP53 mutations.
Chapter 26
Table 26.1 WCRF judgement criteria.
Table 26.2 Sex‐specific risk estimates for increase in body mass index (BMI) by cancer types and gender (where data available).
Table 26.3 WCRF summary judgements on key foods as factors that modify risk of cancer.
Table 26.4 Manchester Cancer Prevention strategy grid (3 × 3 × 3).
Table 26.5 WCRF recommendations on weight, physical activity, and diet to reduce cancer risk.
Chapter 27
Table 27.1 Features of genetic variation conferring cancer risk.
Table 27.2 Proposed classification system for sequence variants identified by genetic testing.
List of Illustrations
Chapter 01
Figure 1.1 The estimated 7.9 million deaths attributed to cancer in comparison to other causes of death. COPD, chronic obstructive pulmonary disease.
Figure 1.2 The most commonly diagnosed cancers in 2012 for males and for females.
Figure 1.3 Prevalence of chronic hepatitis B virus infection among adults.
Chapter 02
Figure 2.1 Contributions of individual/behavioural‐level and policy/societal‐level interventions to addressing the health burden.
Figure 2.2 Prevalence of selected modifiable risk factors in Ontario adults aged 18 and over, 2003–2012.
Figure 2.3 Cervical cancer screening Pap test participation rates among Ontario screen‐eligible women by age group, 2001–2012.
Figure 2.4 Colorectal cancer screening faecal occult blood test (FOBT) participation rates in Ontario by age group, 2005–2012.
Figure 2.5 Percentage of Ontario individuals, 50–74 years old, who were overdue for colorectal cancer screening by age group, 2009–2012.
Chapter 03
Figure 3.1 Each numbered line represents a patient’s course of disease from cancer development to death. The vertical lines represent the potential of routine screening. Horizontal lines 1, 2, and 4 represent patients with disease that would have caused death between scheduled screens. Patients 3, 5, and 6 had slower‐growing tumours that could have been detected by routine screening. Patient 3 had a tumour that was growing so slowly it was detectable in two routine screens.
Chapter 07
Figure 7.1 Infographic showing the contributions of cancer risk factors to the burden of cancer in the UK. Based on data from Parkin 2011 [18].
Chapter 08
Figure 8.1 Effect of cervical screening on the incidence of cancer.
Figure 8.2 Age‐specific incidence of cervical cancer in Scandinavian countries between 1965 and 2005.
Figure 8.3 Age‐standardized incidence of invasive cervical cancer and coverage of screening in the UK, 1971–1975.
Figure 8.4 Age‐standardized incidence of cervical cancer: Comparison between two European countries, Finland and Lithuania.
Figure 8.5 Odds ratio for developing invasive cervical cancer stage IA or worse (in the next five‐year interval) in those screened in a given (three‐year) age band compared with those not screened in that age band (or in two previous years). Odds ratios plotted for overlapping age bands. Broken lines indicate risk of developing cervical cancer at ages 33–40 and 43–65. Odds ratios and confidence intervals are truncated at 1.2. The figure is based on 4012 cases (including 437 in women under age 30) and 7889 controls.
Figure 8.6 Population‐based study showing that the duration of protection increases with age in an organized cervical screening programme.
Figure 8.7 Sensitivity of HPV DNA test to detect HSIL/CIN2+ in comparison to Pap smear in different studies.
Figure 8.8 Specificity of HPV DNA test to detect HSIL/CIN2+ in comparison to Pap smear in different studies.
Chapter 10
Figure 10.1 Age distribution (a) and breast cancer risk (b) of women referred to the Genesis Breast Cancer Risk and Prevention Clinic in Manchester, UK.
Figure 10.2 Distribution of 10‐year breast cancer risks in the UK National Health Service Breast Screening Programme, determined using the Tyrer–Cuzick model and with the addition of visually assessed mammographic density (MD) and 18 single nucleotide polymorphisms (SNPs) related to risk of breast cancer.
Figure 10.3 Recruitment period and numbers of women in each trial (a). Reduction in breast cancer risks (b). CORE, Continued Outcomes of Raloxifene; IBIS, International Breast Intervention Study; MAP3, Mammary Prevention 3; NSABP, National Surgical Adjuvant Breast Project; STAR, Study of Tamoxifen and Raloxifene.
Chapter 14
Figure 14.1 Effect size of the association between known risk alleles and colorectal cancer. Minor allele frequency of the variant shown based on the ethnicity in which the locus was discovered, except for variants with a recessive effect (
MUTYH
), for which frequency for homozygous rare genotype is shown.
Figure 14.2 Colorectal carcinogenesis through defect in the DNA mismatch repair pathway.
Figure 14.3 Colorectal carcinogenesis through the chromosomal instability pathway.
Chapter 16
Figure 16.1 Per capita cigarette consumption and age‐standardized death rates from lung cancer, US males and females, 1900–2011.
Figure 16.2 Title: Age‐adjusted SEER incidence rates for lung cancer, by age at diagnosis, (a) males and (b) females, 1975–2011.
Figure 16.3 Global age‐standardized incidence and mortality rates for lung cancer, by select regions of the world, 2012.
Figure 16.4 Hierarchical model for tobacco control across the life course.
Chapter 19
Figure 19.1 Melanoma age‐standardized incidence and mortality rates (ASRs) in both sexes combined.
Chapter 24
Figure 24.1 Histological section of testicular biopsy specimen: CIS cells are stained dark and are located at the basement membrane of the seminiferous tubule.
Figure 24.2 A theoretical model of TGCT screening.
Chapter 25
Figure 25.1 Surveillance in Li‐Fraumeni syndrome demonstrates improvement in survival.
Chapter 26
Figure 26.1 Summary plots of risk estimates for the associations of body mass index (BMI) and incident liver cancer, by gender and by hepatitis serology status (the latter in a nested case‐control study). The horizontal lines represent risk confidence intervals. Size of box is proportionate to number of participants per category; proportionality is retained across the categories for illustrative reasons.
Chapter 27
Figure 27.1 Finding the full spectrum of genetic variants in complex disease. GWAS, genome‐wide association study.
Figure 27.2 Prostate cancer risk prediction.
Figure 27.3 Polygenic risk and overdiagnosis: Prostate cancer.
Guide
Cover
Table of Contents
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Cancer prevention and screening
Concepts, principles and controversies
EDITED BY
Rosalind A. Eeles, MA (Cantab), PhD, FRCP, FRCR, FMedSci
Professor of Oncogenetics and Team Leader in Oncogenetics,The Institute of Cancer Research,Honorary Consultant in Cancer Genetics and Clinical Oncology,The Royal Marsden NHS Foundation Trust, London, UK
Christine D. Berg, MD
Special Advisor to the Director,Division of Cancer Epidemiology and Genetics,National Cancer Institute,National Institutes of Health, Maryland, USA
Jeffrey S. Tobias, MA (Cantab), MD, FRCP, FRCR
Professor of Cancer Medicine,Department of Oncology,University College London,Honorary Consultant,University College Hospital Foundation Trust,London, UK
This edition first published 2019 © 2019 by John Wiley & Sons, Inc.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.
The right of Rosalind A. Eeles, Christine D. Berg and Jeffrey S. Tobias to be identified as the author of editorial in this work has been asserted in accordance with law.
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Library of Congress Cataloging‐in‐Publication Data
Names: Eeles, Rosalind A., 1959– editor. | Berg, Christine D., editor. | Tobias, Jeffrey S., editor.Title: Cancer prevention and screening : concepts, principles and controversies / edited by Rosalind A. Eeles, Christine D. Berg, Jeffrey S. Tobias.Description: Hoboken, NJ : Wiley, 2018. | Includes bibliographical references and index. |Identifiers: LCCN 2018007656 (print) | LCCN 2018009190 (ebook) | ISBN 9781118991022 (pdf) | ISBN 9781118991060 (epub) | ISBN 9781118990872 (paperback : alk. paper)Subjects: | MESH: Neoplasms–prevention & control | Mass Screening–methods | Global Health | Patient Education as TopicClassification: LCC RC268 (ebook) | LCC RC268 (print) | NLM QZ 250 | DDC 616.99/4052–dc23LC record available at https://lccn.loc.gov/2018007656
Cover design: WileyCover image: Mesh Figures gouache on paper, 2004 © Michael Peckham
List of contributors
Christine D. BergSpecial Advisor to the Director, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Maryland, USA
Otis W. BrawleyChief Medical Officer, American Cancer Society, Georgia, USA
Richard J. BryantCancer Research UK, Royal College of Surgeons of England Clinician Scientist Fellow, Nuffield Department of Surgical Sciences, Oxford Cancer Research Centre, University of Oxford;Honorary Consultant Urological Surgeon, Department of Urology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
John BurnProfessor, Institute of Genetic Medicine, International Centre for Life, Newcastle University, UK
Hilary BurtonDirector, PHG Foundation, Cambridge, UK
Pankaj ChaturvediProfessor, Head & Neck Surgery, Tata Memorial Hospital, Mumbai, India
Susmita ChowdhuryProject Manager and Research Associate, West Suffolk NHS Foundation Trust; PHG Foundation, Cambridge, UK
Jessica S. DoningtonAssociate Professor, Department of Cardiothoracic Surgery, NYU School of Medicine, New York, USA
Louise S. DonnellyResearch Fellow, Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester NHS Trust, Wythenshawe, UK
Rosalind A. EelesProfessor of Oncogenetics and Team Leader in Oncogenetics, The Institute of Cancer Research, Honorary Consultant in Cancer Genetics and Clinical Oncology, The Royal Marsden NHS Foundation Trust, London, UK
Mark ElwoodProfessor of Cancer Epidemiology,School of Population Health, University of Auckland, New Zealand
D. Gareth EvansProfessor of Medical Genetics, Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester NHS Trust, Wythenshawe, UK; The Christie NHS Foundation Trust & Institute of Cancer Sciences; Manchester Centre for Genomic Medicine, St Mary’s Hospital, Manchester Academic Health Sciences Centre (MAHSC), Institute of Human Development, University of Manchester, UK
Kwun M. FongDirector, University of Queensland Thoracic Research Centre, and Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia
Apurva GargSenior Research Fellow, Head & Neck Surgery, Tata Memorial Hospital, Mumbai, India
Aleksandra Gentry‐MaharajTrial Coordinator, Gynaecological Cancer Research Centre, UCL, London, UK
Fiona J. GilbertProfessor of Radiology, University of Cambridge, School of Clinical Medicine; Honorary Consultant Radiologist, University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge, UK
Michelle GriffinHonorary Clinical Fellow, Gynaecological Cancer Research Centre, UCL, London, UK
Andrew E. GrulichProfessor and Head, HIV Epidemiology and Prevention Program, Kirby Institute, University of New South Wales, Sydney, Australia
Alison HallHead of Humanities, PHG Foundation, Cambridge, UK
Freddie C. HamdyProfessor, Nuffield Department of Surgical Sciences, Oxford Cancer Research Centre, University of Oxford; Department of Urology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Michelle N. HarvieResearch Dietitian, Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester NHS Trust, Wythenshawe, UK
Richard J. HillmanAssociate Professor, HIV, Immunology and Infectious Diseases, St Vincent’s Hospital, Sydney, Australia
Jonah HimelfarbInternal Medicine Resident, Division of Hematology/Oncology, Genetics and Genome Biology Program, The Hospital for Sick Children; Department of Pediatrics, University of Toronto, Ontario, Canada
Margaret G. HouseNurse Consultant, National Cancer Institute, Rockville, MD, USA
Anthony HowellProfessor in Breast Oncology, Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester NHS Trust, Wythenshawe; The Christie NHS Foundation Trust & Institute of Cancer Sciences, University of Manchester, UK
Sacha J. HowellSenior Clinical Lecturer, Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester NHS Trust, Wythenshawe; The Christie NHS Foundation Trust & Institute of Cancer Sciences, University of Manchester, UK
Robert A. HuddartProfessor of Urological Cancer, The Institute of Cancer Research, London, UK
Ashfaq KhanConsultant and Head of Colposcopy Service, Whittington Hospital, and Senior Clinical Lecturer, UCL Medical School, London, UK
Fleur Kilburn‐ToppinConsultant Radiologist, University of Cambridge, School of Clinical Medicine; University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge, UK
Jessica KirbySenior Health Information Manager, Cancer Research UK, London, UK
Eric A. KleinChairman, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA
Harry J de KoningProfessor of Evaluation of Screening, Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands
Evan KovacUrologic Oncology Fellow, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA
Kevin LitchfieldDivision of Genetics and Epidemiology, The Institute of Cancer Research; MRC Skills Development Fellow (Bioinformatics), Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK
David MalkinDirector, Cancer Genetics Program, Staff Oncologist, Senior Scientist, Genetics & Genome Biology Program, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Ontario, Canada
Laura A.V. MarlowResearch Associate, Cancer Research UK Health Behaviour Research Centre, Department of Epidemiology & Public Health, UCL, London, UK
Aileen MarshallConsultant in Hepatology, The Royal Free Sheila Sherlock Liver Centre, and UCL Institute of Liver and Digestive Health, Royal Free Hospital, London, UK
Henry M. MarshallClinical Academic Fellow, University of Queensland Thoracic Research Centre, and Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia
Usha MenonResearch Group Lead, Gynaecological Cancer Research Centre, UCL, London, UK
Tim MeyerProfessor, Department of Oncology, UCL Medical School, and UCL Cancer Institute, London, UK
Sabina MusovicResearch Data Coordinator, Department of Cardiothoracic Surgery, NYU School of Medicine, New York, USA
Donald Maxwell ParkinHonorary Senior Research Fellow, Nuffield Department of Public Health, University of Oxford, UK
Howard L. ParnesChief, National Cancer Institute, Rockville, MD, USA
Harvey I. PassStephen E. Banner Professor of Thoracic Oncology, Department of Cardiothoracic Surgery, NYU School of Medicine, New York, USA
Julietta PatnickVisiting Professor, Cancer Screening, University of Oxford, UK
Paul PharoahProfessor of Cancer Epidemiology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
Isobel M. PoyntenSenior Lecturer, HIV Epidemiology and Prevention Program, Kirby Institute, University of New South Wales, Sydney, Australia
Linda RabeneckVice President, Institute for Clinical Evaluative Sciences; Cancer Care Ontario; Department of Medicine, Institute of Health Policy, Management and Evaluation, and Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
David F. RansohoffProfessor of Medicine, Division of Gastroenterology and Hepatology, Department of Medicine; Clinical Professor of Epidemiology, Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA
Andrew G. RenehanProfessor of Cancer Studies and Surgery, Division of Cancer Sciences, School of Medical Sciences, University of Manchester; Manchester Cancer Research Centre and NIHR Manchester Biomedical Research Centre; Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
Monique J. RoobolProfessor in Decision making in Urology, Erasmus University Medical Center, Rotterdam, Netherlands
Arlinda RucoHealth Services Researcher, Institute of Health Policy, Management and Evaluation, University of Toronto; Department of Surgery, St. Michael’s Hospital, Canada
Jonathan M. SametDean and Professor, Colorado School of Public Health, Aurora, USA
Valérie D.V. SankatsingDepartment of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands
Rajiv SarinProfessor, Radiation Oncology & Cancer Genetics, Tata Memorial Hospital, Mumbai, India
Peter David SasieniDirector of King’s Clinical Trials Unit, School of Cancer and Pharmaceutical Sciences, King’s College London, UK
Joanna SestiThoracic and Cardiac Surgeon, Department of Cardiothoracic Surgery, NYU School of Medicine, New York, USA
Harsh ShethResearch Associate, Institute of Genetic Medicine, International Centre for Life, Newcastle University, UK
Albert SingerEmeritus Professor of Gynaecological Research, Institute for Women's Health, UCL, London, UK
Terry SlevinDirector, Education and Research, Cancer Council of Western Australia, Perth, Australia
Andrew J. StephensonDirector, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA
Jeffrey S. TobiasProfessor of Cancer Medicine, Department of Oncology, University College London; Honorary Consultant, University College Hospital Foundation Trust, London, UK
Clare TurnbullProfessor of Genomic Medicine, William Harvey Research Institute, Queen Mary University; Senior Researcher, Division of Genetics and Epidemiology, The Institute of Cancer Research; Honorary Consultant in Clinical Genetics, Department of Clinical Genetics, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
Timothy J. UnderwoodAssociate Professor in Surgery, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, UK
Jane Wardle(now deceased) Formerly:Professor, Cancer Research UK Health Behaviour Research Centre, Department of Epidemiology & Public Health, UCL, London, UK
Sarah WoolnoughExecutive Director of Policy and Information, Cancer Research UK, London, UK
Foreword
Saving lives, saving money, and reducing the huge physical and emotional toll of cancer – the potential gains that can be made through successful cancer prevention and screening should not be underestimated. In the UK, 4 in 10 cancer cases could be prevented, mostly through modifying aspects of our lifestyles which we have the ability to change. Thousands of lives each year are saved through the existing cancer screening programmes. However, there is much scope for improvement, as set out in the chapters in this book.
New screening modalities and refinements to existing screening technologies are in development, which could help save even more lives if the evidence becomes strong enough to support their implementation. More sophisticated risk stratification could lead to tailored screening approaches for individuals or groups, maximizing their efficacy. While these developments hold much promise, research continues to highlight the unintended consequences of screening, and the need for new approaches to minimize harms, as well as clear communication to enable informed decision‐making. Public perceptions of screening are extremely positive, but these strong views should not sway a carefully considered and evidence‐based approach to screening policy‐making.
Legislative changes such as the standardized packaging of cigarettes, and major developments like human papilloma virus vaccination, offer much hope for cancer prevention. But still there are many untapped opportunities. Political discourse on obesity remains predominantly focused on individual choice. We need also to address our obesogenic environment and the influence of industry, while waistlines continue to grow rapidly. The question is, can lessons from tobacco control be transferred to addressing the more complex challenge of obesity?
Our understanding of how and when to deliver health messages for greatest impact is growing, so continued research into successful behaviour change interventions, and making the most of ‘teachable moments’, should prove fruitful. And as we gain more insight into individual risk prediction, this information can increasingly be used to help target prevention – whether lifestyle or medical – to those who will benefit the most. Successful cancer prevention requires upfront investment, but the large pay‐off in savings on cancer care and treatment makes investment in prevention a prudent long‐term approach.
Globally, cancer is becoming an extremely important health problem, including in countries where it has historically not been considered a priority. Increases in longevity, together with high tobacco use and the growing prevalence of obesity, have all contributed to rapidly rising cancer rates in many low‐income countries with scarce resources for treatment. Prevention, therefore, is essential.
Cancer prevention and screening are central to Cancer Research UK's work. Our empowering, accessible, and engaging public information helps raise awareness of the links between lifestyle choices and cancer risk, and our community‐based Roadshow takes nurses into the heart of deprived communities to deliver life‐saving messages with impact. We work with general practitioners and a wide range of health professionals to train, inform, and raise confidence in talking about cancer prevention and screening with patients. We successfully influence for policy changes and government activity to support healthy lifestyles and world‐class, evidence‐based screening programmes.
But effective action on prevention and screening requires many actors working together. From the health professional with a patient, to the marketing we are all exposed to in daily life, nobody can prevent cancer alone. My hope is that increased understanding of the issues surrounding cancer prevention and screening can lead to more effective collaboration and action on these essential issues, and many more lives saved. The potential gains, nationally and globally, are immeasurable.
Sir Harpal S. KumarChief Executive, Cancer Research UK
Prologue
The multitude of different diseases which are generally known by the single word ‘cancer’ continue to plague humankind. As causes of early mortality such as infectious diseases and malnutrition are increasingly brought further under control even in the developing world, life expectancies are beginning to increase globally and in all probability this trend will continue. So we can realistically expect that the incidence of cancer, for the most part closely associated with increasing age, will continue to grow.
By contrast, however, now that we are developing effective preventive strategies such as tobacco cessation and vaccination against oncogenic viruses, coupled with increasingly successful effective screening methods for many malignancies, there are encouraging signs that many of the major cancers are now capable of being prevented, or at least detected earlier, with an increased cure rate as a result. As editors, we felt it would be timely to produce a book which would address these exciting advances in greater detail, in these critically important fields of prevention and screening. One of our key objectives was to provide a truly global perspective, as in our interconnected world the patients we see are from many highly disparate backgrounds, and the medical and scientific communities worldwide can of course learn so much from each other.
We realize that this is a rapidly evolving field. We have chosen internationally recognized experts who present here their insights and opinions in their particular area of focus. As with any book in an area such as this, advances may possibly outpace the accumulation and subsequent publishing of the chapters. Nonetheless, we have great confidence that our chosen chapter authors are well aware of this inevitability and of the current trends well in advance of them becoming common knowledge. We thank all of them most sincerely for their time and expertise and also for their patience in putting up with the revisions which are – invariably – an intrinsic part of any such endeavour. We hope that this book will be of great interest to professionals in many fields of care, from primary care to policymakers. We are also immensely grateful to Sir Harpal Kumar, Chief Executive Officer of the UK’s largest charity, Cancer Research UK, who graciously agreed to write a foreword for us, and to Prof. Sir Michael Peckham, who after a distinguished and varied career as an oncologist and senior academic has now become an acclaimed artist, and kindly allowed us to use one of his striking images for our book cover.
During the gestation of the book our esteemed colleague Prof. Jane Wardle passed away; her contribution to the field of cancer awareness was internationally recognized and we are very privileged that she worked with us as part of this project.
Finally, we would like to thank Dr Michael Sandberg, General Practitioner, London, UK for helpful comments and the editorial and production staff at Wiley‐Blackwell for their dedication, assistance, and foresight in helping us along at every stage of what proved to be a very large project.
We hope you will enjoy reading the book and will learn from it as much as we have done while assembling it.
Rosalind A. Eeles
Christine D. Berg
Jeffrey S. Tobias
CHAPTER 1Global perspectives surrounding cancer prevention and screening
Peter David Sasieni1 and Donald Maxwell Parkin2
1 School of Cancer and Pharmaceutical Sciences, King’s College London, UK
2 Nuffield Department of Public Health, University of Oxford, UK
SUMMARY BOX
The primary approach to cancer control will always be the provision of basic treatment and care. It is inconceivable that this would not be the case because of the immediacy of caring for a sick patient. Without treatment, increased awareness, early diagnosis, and screening are pointless.
Globally, the biggest challenges and greatest successes come from tobacco control and vaccination (against hepatitis B virus and human papilloma virus).
Although not currently associated with any concerted global action, obesity and alcohol control are the next most important challenges for cancer prevention.
Cervical screening is the exemplar of a simple test with the potential to prevent the majority of a particular cancer. Even so, cervical cancer remains a major health problem in most low‐income countries.
Most other forms of cancer screening rely on early detection of invasive cancer and their widespread introduction has been restricted to countries with facilities for diagnosis and treatment.
Screening for early cancers relies on expensive technologies; attempts to use cheap and simple tests have not been successful at a national population level.
Undoubtedly, early diagnosis of cancer has a large impact on morbidity and survival (and subsequent mortality). There is evidence from developed countries that stage distribution has improved over time (more early‐stage disease with a subsequent decline in late stage at presentation). Today, stage distribution in low‐ and middle‐income countries lags behind that of high‐income countries.
Stage at diagnosis can be improved by awareness campaigns, but only when care is available, accessible, and affordable.
Principles of cancer control strategy
Noncommunicable diseases, including cancer, are a current challenge to health services, and one which will increase with the ageing of the world population and changes in lifestyles [1]. The World Health Organization (WHO) strategy is to promote National Cancer Control Programmes (NCCPs) as the most effective approach for reducing the morbidity and mortality from cancer [2]. The development of an NCCP requires adequate information in order to evaluate the nature and magnitude of the cancer burden (and the availability of health‐care infrastructure), as well as the potential impact of the various possible strategies in prevention, early diagnosis/screening, treatment, and palliative care.
Prevention of cancer has to be set within the context of prevention of other noncommunicable diseases, because they have many (but not all) risk factors in common, notably those that are lifestyle related, such as smoking, alcohol, diet, overweight/obesity, and lack of physical exercise. We do not, in this chapter, discuss biomedical approaches to prevention (medication, surgery), because globally they have no role at present.
Early diagnosis is a public and health professional awareness activity, to encourage people to recognize early signs of the cancer and to seek prompt medical attention. Screening involves encouraging asymptomatic individuals to undergo tests to detect early cancer, or precancerous states. Both early diagnosis and screening have to be set within an existing health infrastructure that provides adequate resources for the management of detected cancers (without which such programmes would be ineffective). Because of the considerable resources involved, population screening programmes should be undertaken only when the prevalence of the disease to be detected is high enough to justify the effort and costs of screening, and where resources (personnel, equipment, etc.) are sufficient to cover diagnosis, treatment, and follow‐up of those with abnormal results.
Magnitude of the problem: Proportion of cancer globally attributable to preventable causes
Noncommunicable diseases accounted for about two‐thirds of deaths occurring in the world in 2008 [1]. Considering cancer as a single group, the estimated 7.9 million deaths in that year constituted the leading cause of death (Figure 1.1). In 2012, the most commonly diagnosed cancers were lung cancer (13% of all cancers), breast cancer (11.9%), and colorectal cancer (9.7%); the most common causes of cancer death were lung cancer (19.4% of cancer deaths), liver cancer (9.1%), and stomach cancer (8.8%) [3]. Figure 1.2 shows the numbers of cases and deaths for the most common cancers for males and females.
Figure 1.1 The estimated 7.9 million deaths attributed to cancer in comparison to other causes of death. COPD, chronic obstructive pulmonary disease.
Source: Global Health Observatory Data Repository.
Figure 1.2 The most commonly diagnosed cancers in 2012 for males and for females.
According to Danaei et al. [4], the major environmental causes of cancer death (in 2001) were tobacco, alcohol, and low consumption of fruit and vegetables.
Tobacco smoking is undoubtedly the most important preventable cause of cancer. As estimated by the WHO [5], tobacco was responsible for 22% of the deaths from cancer in 2004 (32% in men, 22% in women), with the major contribution (58% of cancer deaths) coming from lung cancer.
Second in importance in terms of preventable causes of cancer is infection. In 2008, it was estimated that about 16% of the global cancer burden (around 2 million cancers per year) was attributable to infectious agents [6]. The fraction is much larger in low‐income than in high‐income countries. Each of the three principal infectious agents – Helicobacter pylori (stomach cancer), human papilloma virus (HPV; ano‐genital, especially cervical, and oropharyngeal cancer), and the hepatitis viruses HBV and HCV (liver cancer) – is responsible for approximately 5% of the global cancer burden. Much smaller fractions are due to Epstein‐Barr virus (nasopharynx cancers and some lymphomas) and human herpes virus 8 (Kaposi sarcoma), as well as to parasites such as Schistosoma haematobium (liver cancer) and liver flukes (cholangiocarcinoma).
The International Agency for Research on Cancer (IARC) [7] considers that there is sufficient evidence that alcohol consumption causes cancers of the oral cavity, pharynx, larynx, oesophagus, colorectum, liver (hepatocellular carcinoma), and female breast, and also that an association has been observed between alcohol consumption and cancer of the pancreas. The IARC estimated that alcohol was responsible for some 337 400 cancer deaths in 2010, 4.2% of all cancer deaths, with the largest contributions from cancers of the liver and oesophagus (about 23% of such deaths), breast, oral cavity, and colorectum (about 12% each) [7].
Approximately 2.8% of deaths worldwide are attributable to low fruit and vegetable consumption [8]; adequate consumption of fruit and vegetables reduces the risk for cancers of the oral cavity, oesophagus, stomach, and colorectum [9].
Dietary contaminants are a significant problem in some regions; for example aflatoxins, produced by moulds that contaminate cereals and nuts, cause liver cancer, especially in individuals infected with HBV. Aflatoxin has been estimated to have a causative role in 5–28% of all hepatocellular cancers [10].
In 2002, the IARC concluded that overweight and obesity are related to cancers of the colon, endometrium, kidney, and oesophagus (adenocarcinoma), as well as postmenopausal breast cancer. In addition, the report by the World Cancer Research Fund [11] considered that there was convincing evidence for an association with cancers of the pancreas and rectum, and a probable association with cancers of the gall bladder. Overweight and obesity are generally evaluated in terms of body mass index (BMI), with, in ‘western’ countries, a BMI of 25–29.9 kg/m2 being considered overweight, and over 30 kg/m2 obese. Using this definition, Renehan et al. [12] estimated that 5.7% of cancers in Europe in 2008 (3.2% of those in men, 8.6% in women) were caused by overweight/obesity, a figure which is considerably in excess of the 3% estimate (for 2004) for high‐income countries by Danaei et al. [4].
Air pollution is known to increase the risk of respiratory (including lung cancer) and heart diseases. In recent years exposure levels have increased significantly in some parts of the world, particularly in rapidly industrializing countries with large populations. The most recent data indicate that in 2010, 223 000 deaths from lung cancer worldwide resulted from air pollution [13]; exposure to outdoor air pollution is also associated with an increased risk of bladder cancer [14].
The IARC has evaluated indoor emissions from household combustion of coal as carcinogenic to humans [7]. In their earlier assessment, Danaei et al. [4] estimated that 1% of lung cancers worldwide could be ascribed to this cause, but it would be a much larger fraction in China, where most such cases occur [15].
The IARC has classified 32 chemical or physical agents and 11 occupations and industries (for which the responsible agent is not specified) as associated with an increased risk of cancer. The most important are asbestos, diesel engine fumes, silica, solar radiation, and second‐hand tobacco smoke. It is difficult to arrive at global estimates of cancers attributable to occupation, not least because the numbers of exposed persons in a given country may be totally unknown. Driscoll et al. [16] estimated that there were 102 000 deaths from lung cancer, 43 000 from mesothelioma, and 7000 from leukemia due to occupational carcinogens in 2000 (2.4% of cancer deaths). The total of all occupationally induced cancers would clearly be much greater – estimates for developed countries are in the range of 4–8% [7].
Primary prevention strategies globally
Population attributable fractions give an idea of the numbers (and percentages) of cancers that are, at least in theory, preventable. Almost all of those we have discussed have been the object of preventive efforts, ranging from public education and exhortation, to environmental modification and legislative action at a national or more local level. Globally, there are several well‐defined strategies for reducing the burden of cancer.
Tobacco smoking
When the dangers of tobacco smoking became clear, and widely publicized, it was supposed that there would be a reduction in smoking among the public. However, it was soon realized that this was optimistic, and more complex approaches were needed to reduce smoking initiation and promote cessation. Tobacco control programmes are part of national health policy in many countries. Internationally, the WHO initiated a ‘framework convention on tobacco control’ (FCTC), which became a treaty, signed by member states, in 2003 [17]. By June 2013 there were 176 signatories to its legally binding provisions. These include the following:
Demand reduction
Article 6. Price and tax measures to reduce the demand for tobacco.
Article 8. Protection from exposure to tobacco smoke.
Article 9. Regulation of the contents of tobacco products.
Article 10. Regulation of tobacco product disclosures.
Article 11. Packaging and labelling of tobacco products.
Article 12. Education, communication, training, and public awareness.
Article 13. Tobacco advertising, promotion, and sponsorship.
Article 14. Reduction measures concerning tobacco dependence and cessation.
Supply reduction
Article 15. Illicit trade in tobacco products.
Article 16. Sales to and by minors.
Article 17. Provision of support for economically viable alternative activities.
The WHO FCTC also contains provisions for protecting public health policies from commercial and other vested interests in the tobacco industry.
Implementation of the FCTC is monitored by a regular review by the signatories, allowing them to share best practice and present a united, cohesive front against the tobacco industry.
Vaccination
Vaccines are available for two of the important cancer‐causing infections: hepatitis B and Human Papilloma Virus (HPV).
Hepatitis B virus (HBV)
HBV is transmitted by percutaneous and permucosal exposure to infected body fluids. The surface antigen of HBV (HBsAg) may be detected in serum 30–60 days following infection and may persist for widely variable periods of time, with some individuals becoming chronic carriers. The prevalence of HBsAg in the general population globally varies considerably: HBsAg prevalences of more than 8% are typical of highly endemic areas, prevalences of 2–7% are found in areas of intermediate endemicity, whereas in areas with low endemicity under 2% of the population is HBsAg positive. Effective vaccines against HBV have been available since the mid‐1980s and immunization beginning at birth has been introduced into vaccination schedules in many countries (Figure 1.3). Vaccination results in a dramatic reduction of HBV transmission. This will result in a reduction of HBV‐related chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). In Taiwan, where infant vaccination was introduced in 1984, there has been a marked reduction in the incidence of HCC in individuals born since that date, compared with preceding birth cohorts [19].
Figure 1.3 Prevalence of chronic hepatitis B virus infection among adults.
Source: Ott 2012 [18]. Reproduced with permission of Elsevier. Note: This map shows the prevalence of chronic HBV infection among adults (aged 19–49 years) globally in 2005; because this analysis grouped countries together regionally, individual country prevalence may be higher or lower than reflected on the map.
Human papilloma virus (HPV)
Randomized trials have shown the efficacy of two HPV vaccines in preventing infection with virus types 16 and 18 (responsible for about 70% of cervical cancer cases globally) and, more importantly, in preventing cervical intraepithelial neoplasia (CIN) 2 and 3 in females aged 15–25 years [8]. Current vaccines are purely prophylactic; they do not clear existing HPV infection or treat HPV‐related disease. They have been approved and are in use in many countries. The primary target group is young adolescent girls (before the onset of sexual activity); current WHO recommendations [20] are for a two‐dose schedule if vaccination is initiated prior to age 15 years and a three‐dose schedule if immunization is initiated later, but many countries still recommend three doses for all ages.
Routine HPV vaccination has been introduced in many high‐income countries (e.g. most of the European Union (EU) [21] and North America [22]), although coverage rates are lower than expected where vaccination is not school based. However, in low‐ and middle‐income countries (where 86% of cervical cancer cases occur), vaccination has often been implemented, if at all, on a limited scale, frequently as demonstration and pilot projects, funded and operated by nongovernmental organizations (NGOs). Certainly, the challenges are greater and include, in addition to financial constraints, problems in reaching girls for two or three doses in settings where school attendance is low and/or irregular [23].
Other prevention programmes
Preventive strategies to reduce cancer incidence are present in many NCCPs, with the emphasis on the exposures most relevant locally. They may include programmes that aim to reduce overweight and obesity (e.g. through reducing consumption of refined sugars), promote exercise and a healthy diet, reduce alcohol consumption (especially by fiscal measures, or reducing access), and salt intake (voluntary or legislative action on the salt content of foods; the World Cancer Research Fund concluded that ‘salt is a probable cause of stomach cancer’ [24]). None has been the subject of international action like that taken for tobacco and infection.
One area where there is a strong international framework for action is in occupational health. The constituents of the International Labour Organization [25] draw up conventions which are legally binding treaties that may be ratified by member states. Ratifying countries commit to applying the convention in national law and reporting on its application at regular intervals. The conventions most relevant to cancer prevention are as follows:
The Radiation Protection Convention, 1960 (No. 115), setting out basic requirements with a view to protecting workers against the risks associated with exposure to ionizing radiations.
The Occupational Cancer Convention, 1974 (No. 139), which provides for the creation of policy to prevent the risks of occupational cancer caused by exposure to chemical and physical agents of various types present in the workplace.
The Working Environment (Air Pollution, Noise and Vibration) Convention, 1977 (No. 148).
The Asbestos Convention, 1986 (No. 162), indicating reasonable methods of reducing occupational exposure to asbestos to a minimum.
The Chemicals Convention, 1990 (No. 170), providing for the adoption and implementation of a coherent policy on safety in the use of chemicals at work (their production, handling, storage, transport, and disposal).
Medication (tamoxifen or aromatase inhibitors for breast; aspirin for bowel) and prophylactic surgery (oophorectomy and/or mastectomy for BRCA carriers) as approaches to cancer prevention are not discussed here because of their limited scope globally.
Screening
On a global scale, of all the approaches to cancer control, screening is the least effective. The reasons for this are primarily organizational and monetary. Although screening by NGOs is widespread, there is minimal evidence regarding the effectiveness of these well‐meaning interventions, and globally their impact has been minimal.
General principles
Medical screening is an approach to systematically identifying unrecognized disease. In cancer, screening can either be with the intention of identifying cancer early when it has a better chance of being cured, or with the intention of identifying precursor disease that can be treated, thereby preventing it from progressing to cancer.
There is no universally accepted definition of medical screening, but all definitions are based around offering a test to individuals who have not sought medical attention, to identify those who might benefit from further intervention [26]. By definition, testing individuals who consult because of symptoms (no matter how vague) is not screening and will be discussed in the section on early diagnosis.
In 1968, the WHO published the ‘Wilson and Jungner criteria’ for introducing medical screening [27]:
The condition should be an important health problem.
There should be a treatment for the condition.
Facilities for diagnosis and treatment should be available.
There should be a latent stage of the disease.
There should be a test or examination for the condition.
The test should be acceptable to the population.
The natural history of the disease should be adequately understood.
There should be an agreed policy on whom to treat.
The total cost of finding a case should be economically balanced in relation to medical expenditure as a whole.
Case‐finding should be a continuous process, not just a ‘once and for all’ project.
Although the criteria have been debated and modified, they are still widely accepted as sensible. For screening aiming at early diagnosis, it is essential that early‐stage disease should have much lower case fatality than late‐stage. When screening for cancer precursors, one requires that an affordable, acceptable, and effective treatment of the precursor exists.
When most people think about screening they focus on the screening test, but the existence of an accurate test is just one requirement of a successful screening programme. One needs to consider the whole process, from identifying and contacting the target population, through the screening contact (e.g. obtaining a sample or an image), processing that material (e.g. laboratory testing), communicating the result, arranging triage of those who screen positive, and treatment for those with disease. For many screening modalities, a single screen provides only limited protection and it is necessary to arrange for individuals to be rescreened after a suitable interval (e.g. every three years). All these activities need to be quality assured. The history of screening is plagued by stories such as cervical smears being collected using a finger rather than a spatula; slides being looked at by an inexperienced nonspecialist in a poorly lit room; results not being communicated to the individual screened (or worse, the wrong result being communicated); lack of fail‐safe measures to ensure that those in need of treatment receive it; and inadequate treatment that causes more harm than good. It should be clear from this discussion that screening is a multidisciplinary activity that should involve a variety of health‐care professionals. All these activities need to be coordinated and that requires considerable infrastructure. Without such an infrastructure, even the best screening test will have little or no impact in reducing morbidity or mortality.
As with all medical interventions, the most robust evidence for the efficacy of screening comes from randomized controlled trials in which it is demonstrated that those offered screening have a lower incidence of or mortality from a particular type of cancer. Nevertheless, it will usually be necessary first to show an impact on surrogate end‐points. Occasionally the evidence in favour of screening from nonrandomized trials will be so great that there will no longer be equipoise between screening and no screening.
One surrogate that is often discussed in the context of cancer screening is ‘stage shift’. Although a shift in stage is not proof that screening is effective, it is highly unlikely that screening will lead to a reduction in mortality if it does not cause a shift in stage. When claiming a stage shift, many studies simply show that the proportion of cancers diagnosed at early stage has increased. While this is a necessary first step, it is much less powerful than showing that the absolute number of advanced‐stage cancers has been decreased. Almost inevitably, early diagnosis through screening will lead to an (initial) increase in early cancers. However, in order for screening to reduce mortality, it must lead to a reduction in advanced cancers.
Another surrogate end‐point is survival. If screening for occult cancer does not lead to an improvement in survival post diagnosis, it cannot possibly have an impact on mortality. However, a survival benefit alone is not enough, because screening will create a lead‐time bias and screen‐detected cancers will also have a length bias in their survival.
