Long-Term Realism and Cost-Effectiveness: Primary Prevention in Combatting Cancer and Associated Inequalities Worldwide

JNCI Journal of the National Cancer Institute, Dec 2015

The global figure of 14 million new cancer cases in 2012 is projected to rise to almost 22 million by 2030, with the burden in low- and middle-income countries (LMICs) shifting from 59% to 65% of all cancer cases worldwide over this time. While the overheads of cancer care are set to rapidly increase in all countries worldwide irrespective of income, the limited resources to treat and manage the growing number of cancer patients in LMICs threaten national economic development. Current data collated in the recent second edition of The Cancer Atlas by the American Cancer Society and International Agency for Research on Cancer show that a substantial proportion of cancers are preventable and that prevention is cost-effective. Therefore, cancer control strategies within countries must prioritize primary and secondary prevention, alongside cancer management and palliative care and integrate these measures into existing health care plans. There are many examples of the effectiveness of prevention in terms of declining cancer rates and major risk factors, including an 80% decrease in liver cancer incidence rates among children and young adults following universal infant hepatitis B vaccination in Taiwan and a 46% reduction in smoking prevalence in Brazil after the implementation of a more aggressive tobacco control program beginning in 1989. Prevention can bring rich dividends in net savings but actions must be promoted and implemented. The successful approaches to combatting certain infectious diseases provide a model for implementing cancer prevention, particularly in LMICs, via the utilization of existing infrastructures for multiple purposes.

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Long-Term Realism and Cost-Effectiveness: Primary Prevention in Combatting Cancer and Associated Inequalities Worldwide

JNCI J Natl Cancer Inst ( Long-Term Realism and Cost-Effectiveness: Primary Prevention in Combatting Cancer and Associated Inequalities Worldwide Freddie Bray 0 1 2 3 Ahmedin Jemal 0 1 2 3 Lindsey A. Torre 0 1 2 3 David Forman 0 1 2 3 Paolo Vineis 0 1 2 3 0 and/or regional levels , set up for surveillance, primary preven- 1 Torino, Italy and MRC-PHE Center for Environment and Health, School of Public Health, Imperial College London , London, UK, PV 2 Affiliations of authors: International Agency for Research on Cancer , Lyon, France (FB , DF); American Cancer Society , Atlanta, GA (AJ, LAT); HuGeF Foundation 3 tion , early detection, and treatment and integrated into NCD The global figure of 14 million new cancer cases in 2012 is projected to rise to almost 22 million by 2030, with the burden in low- and middle-income countries (LMICs) shifting from 59% to 65% of all cancer cases worldwide over this time. While the overheads of cancer care are set to rapidly increase in all countries worldwide irrespective of income, the limited resources to treat and manage the growing number of cancer patients in LMICs threaten national economic development. Current data collated in the recent second edition of The Cancer Atlas by the American Cancer Society and International Agency for Research on Cancer show that a substantial proportion of cancers are preventable and that prevention is cost-effective. Therefore, cancer control strategies within countries must prioritize primary and secondary prevention, alongside cancer management and palliative care and integrate these measures into existing health care plans. There are many examples of the effectiveness of prevention in terms of declining cancer rates and major risk factors, including an 80% decrease in liver cancer incidence rates among children and young adults following universal infant hepatitis B vaccination in Taiwan and a 46% reduction in smoking prevalence in Brazil after the implementation of a more aggressive tobacco control program beginning in 1989. Prevention can bring rich dividends in net savings but actions must be promoted and implemented. The successful approaches to combatting certain infectious diseases provide a model for implementing cancer prevention, particularly in LMICs, via the utilization of existing infrastructures for multiple purposes. Cancer is one of the leading causes of death worldwide and it The predicted increase in the cancer burden can only be is a major component of the noncommunicable disease (NCD) reduced if primary and secondary prevention strategies are burden. Its societal and economic impact will certainly rise as prioritized. The management of cancer is often extremely morbidity and mortality continue to increase and the demands expensive because of the chronic nature of the disease and on cancer services escalate. Over 14 million new cancer cases the high cost of therapies. LMICs can ill afford the diagnostic occur every year worldwide, but they are projected to reach and therapeutic work-up required by the new wave of cancers the proportion of newly diagnosed cases occurring in low- and middle-income countries (LMICs) is projected to increase from 59% to almost 65% because of the aging and growth of the population but also because of marked increases in the prevalence of known or putative risk factors for cancer associated with west- plans, is likely to have a major impact in reducing the projected burden. Associated Inequalities Worldwide 5 Current data, comprehensively collated for the recent sec- to the built environment (encouraging sedentary lifestyles) and ond edition of The Cancer Atlas released by the American Cancer national policy, including the extent to which multinational however, and the most striking observations of regional div-er tions requiring diagnosis, treatment, and follow-up. Prevention sity come from the comparison of incidence rates (newly occuris much less expensive than implementing all the required ring cases per unit population and time period) and mortality treat cancer patients. However, as we argue later, prevention is dence ratios, a proxy of case fatality, tend to be higher than in better achieved by leveraging upon health care infrastructures, other world regions. In 2012, the ratio for sub-Saharan Africa was which means that prevention and care must go hand in hand, 0.7 (448 000/626 000), compared with 0.4 (692 000/1 786 000) in and at a minimum resource-dependent treatment and palliative North America (US and Canada) (Figure  3). Poverty and infec care services are needed in every LMIC. This paper provides the tion-related cancers are among a number of prominent barrirationale for the feasibility, effectiveness, and cost-effectiveness ers that preclude higher life expectancies in some countries in of primary prevention of cancer in economically developing Africa and other parts of the world (5). Clearly the prevalence of countries. of Cancer The Rapidly Changing Global Landscape If we look at the global burden of cancer, regional diversity is one of the most striking aspects. There are two main features that differentiate LMICs from high-income countries (HICs). risk factors (known or otherwise) and the availability of diagnostics and/or treatment largely determine the magnitude of rates across countries for a specific cancer, for example, cancers of the liver, cervix, colorectum, and prostate (Figure 4). Based on the observations above, global inequalities are a major source of avoidable cancer deaths. In particular, cervical cancer incidence rates in many LMIC countries (including sub Saharan and some Latin-American countries) remain high, and First, LMICs still have a high burden of infection-related cancers, there is also a residual but high burden of HIV/AIDS-related cansuch as cervix and other human papillomavirus (HPV)–related cers in sub-Saharan Africa. This adds to other cancers that are cancers, stomach cancer, and liver cancer. Infection-related can- not preventable based on current knowledge, for example, the cers account for 33% of the total cancer cases in sub-Saharan cluster of unexplained esophageal cancer in Uganda, Zimbabwe, regions compared with only 3.3% in Australia/New Zealand and 4% in North America ( 1 ). Second, LMICs are facing a rapid epidemiologic transition specific to the major NCDs, which are the predominant sources of morbidity and mortality in affluent societies. Similar to the increase in the risk of cardiovascular disease, chronic obstructive pulmonary disease (COPD), and diabetes in many transitioning countries, certain forms of cancer such as lung, colon, and breast cancer are also rapidly rising in these countries (Figure 1). For example, Figure  2 shows the crossing of the curves for breast and cervical cancer incidence over time, a typical indica Malawi, and other Eastern African countries. Diversity is not only related to income, and simple epidemiological transition models often fail to grasp the geographical and temporal heterogeneity of cancer in global terms. While the declines in noncardia gastric cancer can be considered part of an “unplanned triumph” of primary prevention, rates are still very high in parts of Asia including Japan (eg, Miyagi prefecture) and South Korea (Ulsan), China (Cixian), and India (Mizoram). The risk of death from cervical cancer is unacceptably high among young women in middle- and high-income countries of the former Soviet Union (6). This is because of an absence of : / / j n c i . o x f o r d j o u r n a l s . o r g / b y g u e s t o n D e c e m b e r 1 6 2 0 1 5 f Figure 2. The crossing of the curves for breast and cervical cancers is a typical indicator of transition of low-income countries to a pattern typical of high-income r o countries (from Cancer Atlas, American Cancer Society, Atlanta, 2014). The Potential of Prevention is an increasingly important cause of noncommunicable disPrevention has many advantages over cure. There are several eases, including cancer of the liver, upper aero-digestive tract, examples of the effectiveness of prevention, both primary and breast, and colorectum (9). It is slightly increasing worldwide, secondary, in terms of declining cancer rates. Evidently, the though there are strong geographic differences, with increases greatest success in public health in recent decades has been the since the mid-1980s in Russia and more recently since the middecrease in lung cancer mortality in men in most HICs. For exam2000s in China and India and large decreases over the past sevple, 40% of the overall decrease in cancer mortality rate between eral decades in Spain, France, and Italy (10). 1991 and 2003 in men in the United States has been because of In addition to between-country differences, there are large a reduction in cigarette smoking (12). In other cases, a decline in variations within countries linked to socioeconomic position mortality has been achieved by other means, including screenor race/ethnicity. In the United States, survival after a cancer ing. Cervical cancer incidence rates in many western countries diagnosis is much lower in the uninsured than privately insured such as Finland and Sweden have decreased by more than 70%, / / j n c i / / / j n c i rate (world), 2012 (from Cancer Atlas, American Cancer Society, Atlanta, 2014). largely because of organized screening (13,14). In the case of In fact, screening has played a role in decreasing mortality, but breast cancer, mortality in Europe is decreasing in spite of an reasons for the decline go beyond screening per se and include increasing incidence; this is interpreted as the effect of earlier earlier diagnosis due to greater awareness and enhancements diagnosis and more effective therapies at earlier stages (15,16). in breast cancer management and therapy. Curative treatment for prostate cancer in the last 20 years has been a major driver of the age at cessation) (25). As discussed above, certain countries mortality reduction in men in some HICs, while corresponding have been particularly effective in reducing smoking prevalence colorectal cancer mortality trends show declines for similar rea- through taxation and advertisement bans. The chemical arsenic sons including an impact of screening in the United States ( 1 ). is another exposure where elimination rapidly reduces cancer However, colorectal cancer incidence rates continue to increase risk (26). Millions of people are exposed to arsenic poisoning in in young adults in the United States (<50  years of age) and in drinking water in China, Bangladesh, Chile, Taiwan (China), and other HICs (7,17), as they are in many LMICs rapidly transiting other countries, resulting in an increased burden of skin and towards higher levels of development (7). Three Examples of the Preventative Approach in Practice Taiwan and Hepatitis B Virus Vaccination Very good evidence of the effectiveness of hepatitis B virus (HBV) vaccination is available from Taiwan, where vaccination started in 1984. Since then, liver cancer in children and young adults has decreased by as much as 80% (18). As with other preventive programs, the campaign had a number of positive outcomes: It has successfully lowered the prevalence of chronic HBV carriers, mortality from infant fulminant hepatitis, and chronic liver disease in vaccinated birth cohorts. Rwanda and the HPV Vaccine Rwanda, in spite of its limited resources, is at the avant-garde of HPV vaccination, with a stunning 93% coverage of the target population in 2011 (19). This was made possible through schoolbased vaccination and community involvement, a public-private partnership between Merck and the Ministry of Health in developing the program and providing Gardasil free of cost, and a nationwide sensitization campaign that preceded delivery of the first dose (19). This compares with the complete lack of vaccination in the vast majority of African and Asian States. Tobacco Policy in Brazil and Thailand bladder cancers (27). However, sometimes the benefits of cancer prevention can only be observed many years after the intervention. Asbestos is a striking example of a potent carcinogen that still acts for several decades after the removal of exposure, with the persistent increases in asbestos-related mesotheliomas in the UK projected to peak circa 2025, decades after the drastic reduction in exposure ( 28 ). Carcinogens like asbestos that, for biological reasons, take decades to be cleared from the body, require focused attention. The use of asbestos is declining in many countries of the world, but its use is being transferred from HICs to LMICs (Figure  6). The public health benefit of reduced exposure in avoidance of mesothelioma deaths (in terms of numbers) becomes evident only when cohorts reach the ages at which the risk of cancer is sufficiently high. Cancer Prevention as an Economic Investment The costs of cancer diagnosis and therapy are extremely high, while prevention leads to net savings. The combined costs of cancer diagnosis and treatment, loss of productivity because of morbidity and premature death, and informal care costs have been estimated at €126 billion in the EU in 2009, more than the entire EU budget (€112 billion) ( 29 ). The direct medical costs (total all healthcare expenditures) in the United States in 2011 were estimated to be around $88.7 billion per year (30). There are no similar data on cost of cancer from LMICs. However, costs are likely to increase, both in HICs because of expanding costs of therapies and in LMICs because of the increasing burden of cancer. Tax and prices of tobacco are among the most effective policies In the absence of the implementation of prevention, LMICs on the side of demand. There is strong evidence from Thailand will not have the resources to diagnose and treat all new cancer and Brazil that increases in taxes and prices had a large and patients, and the economic burden will soon become unsustaindurable impact on the decline in tobacco use (20,21). In Brazil, able. Such a scenario can only amplify socio-economic differensmoking prevalence declined by 46% between 1989 and 2008, tials, making effective therapies a preserve of the richest in most with 48% and 14% of the relative decline attributed to taxes societies. There are many examples of a complete lack of essenand advertisement bans, respectively (20). Similarly, increased tial infrastructure to presently tackle cancer in LMICs. Ethiopia, taxes and advertisement bans, respectively, accounted for 61% the second most populous country in Africa with a population and 22% of the relative decrease in smoking prevalence between of over 80 million, is presently served with only two function1991 and 2006 in Thailand (21). Other examples of the effectiveing radiotherapy machines (31). Africa and other less developed ness of the increasing price of cigarettes on reducing cigarette regions in general are very poorly served when it comes to radiconsumption come from South Africa and France (22). The otherapy availability ( 1,31 ). Despite 60% of the cancer burden Framework Convention on Tobacco Control (FCTC), the world’s falling on LMICs, only 32% of the radiotherapy machines availfirst global health treaty, entered into force in 2005 and contin- able worldwide are operating on the continent. ( 1 ) This is the ues to provide an impetus for further tobacco control in coun- case with other indicators of very limited health infrastructure: tries around the world (23). For example, with the exceptions of South Africa and Botswana, The different timing in the perception of benefits of precountries in sub-Saharan Africa average less than one patholovention has to be considered because politics often suffers gist per 500 000 people (32). from “short-termism.” For certain risk factors the impact of While introducing screening for colorectal and breast can prevention can be demonstrated soon after implementation. cers is not only cost prohibitive but may not be supported by Reducing smoking leads to a substantial reduction in risk of existing healthcare infrastructure in most LMICs, most prevenlung cancer and cardiovascular disease a few years after cestive activities are relatively cheap and feasible to implement, sation (24). However, eliminating smoking uptake is the optiincluding tobacco control as described in the FCTC’s MPOWER mal policy, as risk among former smokers does not return to measures (higher tobacco taxes, dissemination campaigns on the levels of never-smokers for several decades (depending on health risks of smoking, restrictions on smoking in public places) D o w n : / / j n c i / b y g u e s t o n D e c e m b e r 1 6 2 0 1 5 / / j n c i . o x f o r d j o u r n a l s . o r g / b y g u e s t o n D e c e m b e r 1 6 2 0 1 5 cer Atlas, American Cancer Society, Atlanta, GA, 2014; adapted from: Virta RL. Worldwide asbestos supply and consumption trends from 1900 through 2003: U.S. Geological Survey Circular 1298. Reston, VA; United States Geological Survey; 2006. Available frohmttp://pubs.usgs.gov/circ/2006/1298/c1298.pdf, accessed July 25, 2014.). * The top seven Western European consumers in 1970: UK, Italy, W. Germany, E. Germany, France, Spain, and Belgium/Luxembourg. †USSR for 1970; Russia and Kazakhstan for 2003. (4), dietary advice, and a policy on prices that promotes healthy needed in LMICs. Secondly, leveraging on existing health care diet (33). Comprehensive cervical cancer prevention programs infrastructures has been an effective way to promote prevenare feasible and cost as little as $0.20 per capita in the ten coun- tion for infectious diseases. The way forward has been shown by tries that currently have the highest mortality rates in the world the successful approaches adopted to tackle infectious diseases (Mali, Guinea, Burundi, Zambia, Zimbabwe, Tanzania, Comoros, such as HIV/AIDS, using the existing infrastructures for multiple Mozambique, Malawi, and Swaziland) ( 34 ). Equally, there would purposes (though the role of highly active antiretroviral therapy be enormous dividends in LMICs following complete coverage for AIDS has been crucial, while a similar life-saving treatment of HPV vaccination: The cost to avert one disability-adjusted is currently unavailable for most cancers, an additional reason life-year is less than gross domestic product per capita, which to promote prevention). The issues involved in improving the makes it a very cost-effective intervention by World Health responsiveness of health systems to NCDs have been reviewed Organization standards (costs at the price negotiated by the by Atun et al. (39). They note that management of NCD patients, Global Alliance for Vaccine and Immunization (GAVI)) (35). sometimes with multiple conditions, is particularly challenging Often, risk factors are shared among many different diseases. in low- and middle-income countries with weak health systems, For example, smoking, obesity, and poor diet are risk factors for characterized by fragmented health care services. A key lesson several major cancers but are also determinants of cardiovasfrom HIV/AIDS is the broad-based governance in identification cular disease, diabetes, and some neurological diseases. Thus of problems, needs, and responses, involving the engagement prevention has an impact on multiple NCDs. There are several of civil society, affected communities, and the private sector. examples of how preventive activities might lead to net savAtun and colleagues have shown the efficacy of an integrated ings. The smoking cessation program in Taipei (involving counapproach for infectious diseases and a possible pathway for seling and nicotine replacement) led to 215 million USD savings combatting NCDs. The first steps in this direction may be seen, in 15 years (36). According to a simulation model, an intensive for example, with implementation of HBV and HPV immunizasix-month mass media antismoking campaign in Australia will tion, particularly in GAVI-eligible countries; however, one must lead to an estimated $912 million savings over the lifetime of also have actions focussed on supporting the implementation of 190 000 quitters (37), which is equivalent to Australia’s govern- the HPV vaccine nationally in noneligible LMICs (39). ment investment in early childhood education. Dietary advice to Leveraging existing public health infrastructure is an imp-or obese and overweight people in the Netherlands has been estitant strategy for cancer control in LMICs, where resources to mated to save up to $2.5 billion over five years (38). Implementing Prevention Using Existing Infrastructures address the burden of chronic disease are limited. The United States Centers for Disease Control and Prevention (CDC) works with Ministries of Health and other partners to establish sustainable Field Epidemiology Training Programs (FETPs: http://www. cdc.gov/globalhealth/FETP/default.htm), which help to build and What is the best strategy to implement prevention in the most strengthen workforce capacity for disease detection, laboratory effective way, particularly in LMICs? Noncommunicable diseases, including cancer, need to be prioritized, and prevention is a good investment.The promotion of national, universal healthcare systems would be a leap forward for cancer control in every country, if coupled with sound public health initiatives. Prevention implementation must therefore be integrated with cancer diagnosis and care for two reasons. One is that a minimum level of good quality disease management (including palliative care) is services, and outbreak response. Since 1980, 50 of these programs have produced more than 2800 graduates in 69 countries, with more than 80% of graduates serving as public health leaders in their home countries. There is great potential to leverage FETP infrastructure and expertise to build capacity and leadership for the prevention and control of cancer and other chronic diseases; the program has already begun to reach into NCDs through five initial NCD focus countries (China, Colombia, Jordan, Tanzania, and Thailand). The Pink Ribbon Red Ribbon (PRRR: http://pinkribbonredribbon.org/) initiative is an innovative public-private partnership that uses evidence-based approaches to deliver health care services for women’s cancers in sub-Saharan Africa. PRRRsupported programs increase access to cervical cancer screening and treatment, HPV vaccine, and breast and cervical cancer education for underserved women in this region. Similarly, GAVI (http://www.gavi.org/pledging2015/) has worked with the World Health Organization Expanded Program on Immunization to prevent cervical cancer in low income countries by increasing access to HPV and HBV vaccines. Another example is the IARC-coordinated Global Initiative for Cancer Registry Development (GICR; http://gicr.iarc.fr), which has brought together a group of major international and national agencies to work collaboratively to redefine the level of cancer surveillance worldwide for cancer control action. Advocating the central role of population-based cancer registries in national planning, reference centers (IARC Regional Hubs) are becoming cancer control implementation, monitoring, and evaluation. The World Health Organization has endorsed the GICR as a tool to support Member States in addressing the related indicator (cancer incidence by type per 100 000) within the NCD Global Monitoring In the absence of prevention, the cancer burden will soon become overwhelming in many lower-income countries in sub-Saharan Africa, Asia, Latin America, the Caribbean, and the Pacific Islands because of the aging of the population, tobacco and other risk factors, and a chronic lack of adequate medical and public health infrastructure. This is one of the central arguments to accelerate the implementation of primary prevention while the opportunity This commentary was written by staff of the American Cancer Society (A. Jemal and L.  Torre), the International Agency for Research on Cancer (F. 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Freddie Bray, Ahmedin Jemal, Lindsey A. Torre, David Forman, Paolo Vineis. Long-Term Realism and Cost-Effectiveness: Primary Prevention in Combatting Cancer and Associated Inequalities Worldwide, JNCI Journal of the National Cancer Institute, 2015, DOI: 10.1093/jnci/djv273