The global cancer burden & cancer prevention strategies

1. Introduction

Cancer is the second most common cause of death globally, accounting for an estimated 9.6 million deaths in 2018. The cancer burden is rising globally – but not equally. The greatest impact of cancer and the fastest increase in the cancer burden over the coming decades is projected to be in low- and middle-income countries, many of which already face difficulties coping with the current burden. A large proportion of those cases can be prevented and even when prevention is not possible, early diagnosis saves lives.

This IARC World Cancer Report 2020 is based on purpose-made assessments, prepared by recognized investigators worldwide and published after undergoing peer review. It presents the most comprehensive, up-to-date science on cancer prevention, including statistics, causes, and mechanisms, and how this can be used to implement effective and resource appropriate strategies for cancer prevention and early detection.

2. What are the global strategies to limit the burden of cancer?

At the United Nations General Assembly in 2018, world leaders agreed to take responsibility for preventing and treating cancer (and other non-communicable diseases (NDC)), to protect people from cancer causing products, to promote evidence-based treatment, and to work towards universal health coverage. To this end, robust, independent scientific evidence is critical, focused on the scale and patterns of cancer and its causes, prevention, and early detection.

The International Agency for Research on Cancer (IARC), working with researchers around the world, is essential for the development of evidence-based guidelines and policy by WHO, and for regulatory decisions by national institutions to protect the health of their populations through successful prevention strategies to translate the latest knowledge into actionable policies to support governments.

3. What does this new World Cancer Report provide?

This new World Cancer Report provides cancer researchers, health-care professionals, regulators, and policy-makers with detailed information across a broad perspective and multidisciplinary spectrum about the causes of cancer, its prevention, and other matters tending to reduce its burden. It provides a “bottom line” which is crucial in several respects as it ensures that all relevant findings are considered and including human circumstances not necessarily taken into account from the sole knowledge of biological mechanisms. Avoiding exposure to a known carcinogen, for example, cannot always encompass why different tumour types are particularly prevalent in some populations and not in others; moreover, currently available research on several cancer types, including prostate cancer, brain cancer, and leukaemia, does not allow a clear proportion of these malignancies to be attributed to particular exogenous factors.

When taken together, the 20 types of cancer that are covered account for the overwhelming majority of cancer cases worldwide and, of greater importance, account for almost all initiatives aimed at cancer prevention. Priority was given to recent epidemiological findings that have contributed to an increased understanding of etiology or, in some rare cases, prevention.

Nevertheless, there is no generally operative procedure that determines the transition from cancer research findings to cancer prevention policies and the words “cancer research for cancer prevention” essentially contribute to identify a pathway that may reduce the acknowledged burden of cancer faced by humanity.

To note that to curb the rising burden of NCDs, WHO proposed a “best buys” package to facilitate interventions that are feasible, affordable, and cost-effective and that the WHO Report on Cancer: Setting priorities, investing wisely and providing care for all – complements the IARC World Cancer Report.

4. How is cancer burden distributed over the world?

Although mortality rates from cancer are declining in most higher-income countries, such progress is lacking in lower-income countries and cancer remains the first or second leading cause of premature death (i.e. at ages 30–69 years) in 134 of 183 countries. It ranks third or fourth in an additional 45 countries. Of the 15.2 million premature deaths from non-communicable diseases worldwide in 2016, 30 % were due to cancer.

There are marked differences between countries or regions in cancer mortality, with an increasing burden in low- and middle-income countries, attributable both to less-than-optimal implementation of preventive measures and to diagnosis at a late stage of cancer development.

More specifically, cancer has surpassed cardiovascular diseases as the leading cause of death in countries with high or very high Human Development Index (HDI)¹. In contrast, cardiovascular diseases remain the leading cause of death in lower-income countries.

The distinct patterns of causes of death such as behavioural factors (e.g. tobacco use, harmful alcohol consumption), unhealthy diet, and physical inactivity, metabolic factors (e.g. high blood pressure, overweight and obesity, and high cholesterol level), and environmental factors would thus help to prioritize approaches to reduce mortality from specific major causes in a given country. Lower-income countries face also the additional burden of poverty-related non-communicable diseases, such as infection-related cancers (including stomach, liver and cervical cancers).

Feasible, affordable, and cost effective interventions that reduce exposure to the key causes and other risk factors for cancer, increased access to essential health-care services and vaccines are crucial for disease control globally. For example, whereas cancer surgery services are available in 95% of high-income countries, the equivalent rate is only about 25% in low-income countries.

It is in this context that the United Nations, within the Sustainable Development Goals agenda², has set an overarching target (Target 3.4) to reduce the total premature mortality from non-communicable diseases including cancer by one third by 2030 would lead to a further gain of 20% in average expected years lived.

¹ HDI is an indicator of national achievement in attaining a long and healthy life (based on life expectancy at birth), acquiring knowledge (based on average and expected years of schooling), and achieving a decent standard of living (based on gross national income per capita).
² www.un.org/sustainabledevelopment/development-agenda/ 

5. What are the global trends in cancer incidence and mortality?

For several tumour types – colorectal, prostate, lung and breast cancer – high incidence rates were once restricted to North America, western Europe, and Australia while low income countries primarily had a relatively high incidence of stomach, liver, and cervical cancer. Now, changes in incidence over time for these and other cancer types illustrate an evolution and variations between countries. Evidently there are increasing global inequalities in cancer control planning and outcomes. The predicted global cancer burden is expected to exceed 27 million new cancer cases per year by 2040, a 50% increase on the estimated 18.1 million cancers in 2018. The estimated increases in the cancer incidence burden from 2018 to 2040 using demographic changes will occur in all countries, but the predicted increases will be proportionately greatest in countries with low and medium HDI. Presently, a high residual burden of infection-related cancers is observed in countries with low HDI but there are clear examples of national and regional cancer diversity of cancer occurrence that depart from this model.

• Tobacco smoking is responsible for 63% of overall global deaths from lung cancer and for more than 90% of lung cancer deaths in countries where smoking is prevalent in both sexes, and lung cancer survival remains low globally;
• Rising breast cancer incidence rates, for example, are correlated with trends towards earlier ages at menarche, later ages at first birth, and lower parity. In countries with high income, incidence rates have stabilized after a marked decline in incidence starting in about 2000, which is considered to result from the publication of two landmark studies that reported on the harmful effects of menopausal hormone replacement therapy on breast cancer risk which, with earlier detection through earlier diagnosis and effective screening programmes, may in part explain these favourable trends; 
• Incidence rates of colorectal cancer have increased in countries in transition and in younger age groups and in recent generations in a diverse set of countries. Declining incidence trends are observed predominantly in older age groups (55 years and older) of some HDI countries subject to early detection programmes that detect and remove precancerous colorectal polyps, leading to a decline in malignancies while other factors may have contributed, including the adoption of preventive therapies such as regular use of aspirin, postmenopausal estrogen therapy, or – as a matter of greater speculation – an increasing intake of vitamin D; 
• The evolution of observed prostate cancer incidence rates (an increase followed by a decline, as observed in the USA) is attributed to the clinical testing of a prostate specific antigen (PSA);  
• Stomach cancer, which ranks 5^th in terms of incidence and 3^th in terms of mortality, is decreasing (predominantly the non-cardia type with 75–90% attributable to infection with Helicobacter pylori), whereas incidence of cancer of the cardia region of the stomach strongly associated with overweight and obesity is increasing in several populations;  
• As a result of the detection of precancerous lesions by screening, cervical cancer incidence and mortality rates have declined in most countries in recent decades. The general consensus is that these trends relate to changes in sexual behaviour and increased transmission of persistent human papillomavirus (HPV) infection among birth cohorts. Global elimination of the disease is attainable during this century through HPV vaccination and screening programmes even if increasing rates have been observed in younger generations of women in some countries.  
• Chronic infections are the cause of about 13% of cancers worldwide, or 2.2 million cases per year. Eleven infectious agents, or groups of related agents, are established human carcinogens, including one bacterium, seven viruses, and three macroparasites with Helicobacter pylori, human papillomaviruses, hepatitis B virus, and hepatitis C virus contributing most to the burden of cancer caused by infections globally. Chronic infection with hepatitis B virus and hepatitis C virus resulted in about 360 000 cases and 140 000 cases, respectively, of hepatocellular carcinoma in 2018, amounting to about 76% of all cases of hepatocellular carcinoma. Preventive vaccines against hepatitis B virus have been available since 1982, and direct-acting antiviral agents have the potential to cure more than 95% of people with hepatitis C virus infection. And if, for Helicobacter pylori, all of the vaccines currently under development are at an early stage, there appears to be little, if any, investment from large pharmaceutical companies at this stage.

In women, the 5-year prevalence burden in each HDI tier generally had a similar profile of cancer types to that observed for incidence. In 2018, the cancer profile by HDI level varied more substantially in men than in women. In terms of incidence, lung cancer was the most common type in the medium high and very high HDI tiers, whereas prostate cancer was the most common type in the low and very high HDI tiers. Liver cancer and colorectal cancer were also among the most common causes of cancer mortality in all four HDI tiers.

The increase in life expectancy for individuals aged 40–84 years for the period 2006–2010 was 2.5 years for men and 1.9 years for women in countries with very high HDI, whereas the increases were only 1.6 years for men and 1.5 years for women in countries with medium or high HDI.

6. Is cancer a major cause of death in children?

Cancer is indeed a major cause of death in children, and the incidence of childhood cancers is increasing worldwide in both high- and low-income regions. In children, cancer types are different from those in adults, the most common cancer types are leukaemia, lymphoma, and tumours of the central nervous system. However, the causes of childhood neoplasms are largely unknown; only about 5% of tumours are of hereditary origin, and ionizing radiation is the only ascertained environmental carcinogen. For many agents, such as benzene, arsenic, and dioxins, the evidence of carcinogenicity is well established in adults but only limited in children. Like in adults, many cancers in children are thought to be activated by somatic mutations but, the relative rarity of cancers in children and the difficulties in evaluating what children might have been exposed to early in life make it difficult to establish a causal role of the environment.

Compared with adults, children are also more vulnerable to environmental agents, because of their unique activity patterns, behaviour, and physiology, as well as the immaturity of their organs; in addition, many children – especially those living in low-income regions of the world – are involved in hazardous work, such as that involving contact with pesticides, and are exposed to emerging threats such as toxic components of electronic waste (e-waste).

7. What are the main basis for cancer prevention strategies?

Cancer incidence can be reduced by decreasing or eliminating exposure to carcinogens in multiple contexts. Evidence from comprehensive community programmes suggests that a combination of behavioural theory, commitment, and national and local action are key factors in the design of programmes and policies.

Two of the most notable successes in prevention have been through tobacco control and vaccination policies. Success in reducing the incidence of smoking-related cancers in some countries indicates a range of measures that may be researched for their efficacy in other situations. Interventions to change behaviour related to nutrition, exercise, and weight gain are being actively researched.

 

 

Vaccination is effective for some cancers caused by infectious agents. Deaths from sporadic cancer may be decreased through chemoprevention and diagnosis of early-stage disease by screening and emerging molecular methods of early diagnosis. The hepatitis B virus vaccine was the first vaccine designed to prevent a major human cancer type. Thirteen high-risk human papillomavirus types, particularly HPV type 16, cause cervical cancer (about 570 000 new cases per year in 2018) and anal cancer, and substantial fractions of cancers of the vulva, vagina, penis, and oropharynx. Comprehensive data document the safety and high efficacy of HPV vaccines, especially in adolescent girls, who are the priority target for HPV vaccination.

Infections with hepatitis C virus, Helicobacter pylori, and the macro-parasites are curable. For HIV and hepatitis B virus, infections can be controlled by antiviral treatment to reduce the risk of cancer and of transmission to others.

An increased risk of cancer may also be indicated by family history and can be addressed by monitoring the affected individuals. The extent to which the options summarized here are realized across national boundaries warrants continuing research.

Despite advances in evidence based interventions, widespread implementation of prevention strategies varies between countries. For effective prevention practices, the cultural context, measurement strategies, and sustainability for implementation must be considered. There is for example continuing development in the areas of nutrition and physical activity, among other prevention strategies.

For women at high risk of breast cancer, reductions of 30–70% in the incidence of breast cancer can be achieved with use of anti-estrogenic agents such as tamoxifen. Also widespread use of low-dose aspirin for 10 years between ages 50 years and 65 years could have a major impact on cancer incidence and mortality.

Low-dose aspirin stands out as having the largest potential impact on the population at large.

There is indeed now overwhelming evidence for a reduction of about one third in colorectal cancer incidence and mortality from long-term regular aspirin use. Beneficial effects of a similar size have been seen for oesophageal cancer and stomach cancer, and smaller, less convincing reductions of 5–15% have recently also been found for lung cancer, breast cancer, and prostate cancer, but there appears to be little or no effect on other major cancer sites.

Advances in sequencing technology have enhanced knowledge about the genes and pathogenic or likely pathogenic variants associated with hereditary cancer and have increased access to more affordable and comprehensive genetic testing. Options are available for cancer risk reduction in carriers, including lifestyle changes, enhanced surveillance, chemoprevention, and risk-reduction surgery. However, evidence on the efficacy and cost–effectiveness of these interventions has been generated only for high-penetrance genes such as BRCA1 and BRCA2, and most guidelines cite inadequate evidence for some or all aspects of management for moderate-risk gene variants, for which more work is needed to calibrate risks and interventions.

Early detection of cancer is another critical component of cancer control. In addition to reduction of mortality from a specific cancer type, a proper approach to cancer screening should ensure that the harms do not outweigh the benefits. The natural history of the disease does not enable understanding of the differences between indolent, less aggressive, and aggressive tumours. The prevailing linear approach to identifying tumours with aggressive behaviour that merit early detection must be overcome. Over-diagnosis of indolent tumours and the morphological basis of cancer diagnosis are the most relevant challenges in searching for alternative approaches to cancer screening. This challenge can lead to both over- and under-treatment of cancers detected by screening. The hallmarks of cancer may offer a new approach to cancer screening by combining oncoproteins, cell damage markers, and epigenetic markers.

Public health capacity is a key variable that underpins the successful implementation of programmes. When evaluating and implementing a programme, cues can be taken from other strategies that have proven effective in building capacity.

 

 

Sustainable implementation requires organizing and maximizing community assets and resources, institutionalizing policies and practices within communities and organizations, considering the context and infrastructure of the community, and involving a multiplicity of stakeholders who can develop long-term buy-in and support.

Cancer prevention: the basis for, and outcomes from, prevention strategies
Tobacco cessation	Managing people with high and moderate genetic risk
Changing behaviour	Screening, from biology to public health
Improving diet and nutrition, physical activity, and body weight	Circulating DNA and other biomarkers for early diagnosis
Vaccination	Governmental action to control carcinogen exposure
Preventive therapy	Prevention strategies common to non communicable diseases

In addition to the characteristics of the intervention, the capacity of the public health infrastructure and the health delivery system to implement and sustain a prevention strategy is fundamental. Universal access to health care is important for the delivery of the preventive intervention and also for cancer care and outcomes of care.

The field of implementation science offers innovative approaches to identify, understand, and develop strategies for overcoming barriers to the adoption, adaptation, integration, scale-up, and sustainability of evidence-based interventions, tools, policies, and guidelines. Expanding the focus of implementation science to include policy research could be very fruitful.

Future priorities in the area of changing behaviour include:

1. identifying the components of interventions that are key to sustained change, and those that are most readily adapted to fit a population group;
2. a clearer understanding of when prevention strategies are not adequate and should be abandoned or replaced;
3. a greater use of implementation science to move from research to broader application of prevention strategies;
4. maintaining programmes for the sustained achievement of desirable goals and population outcomes;
5. a better understanding of the benefits of prevention through the leading modifiable risk factors and the benefits that extend beyond individual countries.