YGYNO-975831; No. of pages: 6; 4C: Gynecologic Oncology xxx (2015) xxx–xxx

Contents lists available at ScienceDirect

Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno

Review

Global health perspective on gynecologic oncology Marcela G. del Carmen a,⁎, Laurel W. Rice b, Kathleen M. Schmeler c a b c

Division of Gynecologic Oncology, Vincent Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States Department of Obstetrics and Gynecology, University of Wisconsin Hospital and Clinics, Madison, WI, United States Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States

H I G H L I G H T S • An estimated 80% of global cancer burden and only 5% of global cancer spending affect LMICs. • Prevention is central to global health efforts to close the cancer divide.

a r t i c l e

i n f o

a b s t r a c t Objective. To describe challenges faced by low-middle income countries (LMICs) across the cancer spectrum, with specific focus on gynecologic cancers. Methods. MEDLINE was searched for research articles published in English between January 1, 2000 and February 1, 2015 which reported on global health efforts in LMICs. Results. An estimated 80% of global cancer burden and only 5% of global cancer spending affect LMICs. The overwhelming majority of cervical cancer cases and related deaths occur in LMICs. The charge to close this cancer divide is at the center of global health efforts. Conclusions. Prevention is central to global health efforts to close the cancer divide. The gynecologic oncology community is well positioned to lead efforts in global health by partnering with institutions, professional societies and advocacy groups. © 2015 Elsevier Inc. All rights reserved.

Article history: Received 15 February 2015 Accepted 9 March 2015 Available online xxxx Keywords: Global Health Low-middle income countries

Contents 1. 2.

3.

4. 5.

Introduction . . . . . . . . . . . . . Cancer incidence . . . . . . . . . . . 2.1. Cancer among women . . . . . 2.2. Economic burden of cancer . . . 2.3. Objective . . . . . . . . . . . Primary prevention . . . . . . . . . 3.1. Tobacco . . . . . . . . . . . 3.2. Physical activity, diet, and obesity 3.3. Infection . . . . . . . . . . . 3.4. Environmental factors . . . . . Secondary prevention . . . . . . . . Treatment . . . . . . . . . . . . . . 5.1. Surgery . . . . . . . . . . . 5.2. Radiation therapy . . . . . . . 5.3. Systemic therapy . . . . . . . 5.4. Surveillance/survivorship . . . 5.5. Palliative care . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . .

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

⁎ Corresponding author at: Division of Gynecologic Oncology, Vincent Obstetrics and Gynecology, Massachusetts General Hospital, 55 Fruit Street, Yawkey 9E, Boston, MA 02114, United States. Tel.: +1 617 726 1940; fax: +1 617 724 6898. E-mail address: [email protected] (M.G. del Carmen).

http://dx.doi.org/10.1016/j.ygyno.2015.03.009 0090-8258/© 2015 Elsevier Inc. All rights reserved.

Please cite this article as: del Carmen MG, et al, Global health perspective on gynecologic oncology, Gynecol Oncol (2015), http://dx.doi.org/ 10.1016/j.ygyno.2015.03.009

2

M.G. del Carmen et al. / Gynecologic Oncology xxx (2015) xxx–xxx

6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction Global health represents the intersection of interests inherent to public health and international health, focusing on population-based prevention, health care delivery to underserved and vulnerable populations, as well as multi- and interdisciplinary efforts engaging stakeholders in structuring and delivering health services [1,2]. It seeks to promote social/economic equity and eliminate health care disparities [1]. Central to global health efforts is the charge to alleviate the impact of cancer and poverty on each other. Poverty and limited access to education and health care services result in increased risk for developing and dying from malignancies. In turn, health care costs and long-term disability result in impoverishment affecting individuals, families, communities and the health care system. According to the World Economic Forum, chronic disease impacts global productivity and economic development, ranking it as one of the three leading global economic risks (the other two, water crises and weapons of mass destruction) [3]. The last decades have seen unprecedented advances in ease/speed of travel, communication, and economic interdependency among nations [1]. Health and medicine are at the forefront of this globalization process, offering an opportunity for social change. 2. Cancer incidence In 2012, there were 14.1 million new cancer cases, 32.6 million people living with cancer (b5 years from diagnosis), and 8.2 million cancerrelated deaths worldwide [4]. Women accounted for over 6.6 million new cases and 3.5 million of these deaths [4]. A total of 214 economies are classified by the World Bank, 139 (65%) fall under the low and middle income country (LMIC) category [5]. Approximately 62%, 25%, and 13% of the world's population lives in low-, middle-, and high-income countries (HICs), respectively [5]. The majority of the world's cancer burden occurs in LMICs, with 8 million (57%) new cancer cases and 5.3 million (65%) cancer-related deaths per year [4]. 2.1. Cancer among women The ten most prevalent cancers among women worldwide include breast, colorectal, lung, cervix, stomach, uterus, ovary, thyroid, liver

and non-Hodgkins lymphoma (NHL). For the majority of these malignancies, the incidence and mortality is higher in LMICs compared with HICs (Fig. 1). The largest disparity is seen with cervical cancer, with the overwhelming majority of cases and related deaths occurring in LMICs in Latin America and sub-Saharan Africa. In 2012, there were 83,000 new cervical cancer cases and 35,000 related deaths in HICs compared with 444,000 new cases and 230,000 related deaths in LMICs [4]. Of those, 93,225 cases and 57,381 deaths were in sub-Saharan Africa, and 83,195 cases and 35,673 were in Latin America [4]. 2.2. Economic burden of cancer The global costs associated with cancer are significant and are estimated to comprise 2–4% of the annual gross domestic product (GDP) [6]. By 2035, 24 million new cancer cases and 14.6 million deaths will occur in LMICs [1]. For women, incidence and mortality are projected to increase for all cancers, including gynecologic malignancies (Fig. 2). This crisis constitutes a challenge to all global health efforts, threatening to increase human suffering and further devastate economic growth. Despite over 80% of the global cancer burden occurring in LMICs, only 5% of global cancer spending is focused on these countries [4,6]. The cost of increasing access to cancer treatment globally is not as high as expected. The estimated global annual cost of unmet medical treatment for cervical cancer is $26 million [4]. The impact that cancer has on a population reflects issues of equity since access to cancer prevention and treatment and cancer care for the poor are much more limited than for the wealthy, and largely determined by geography and income [6]. While LMICs continue to battle against diseases associated with poverty/underdevelopment, they face a growing challenge, what has been termed the cancer divide [4,6,7]. The disproportionate burden in cancer incidence and mortality shouldered by LMICs represents a cancer divide with a mandate, at the core of all global health efforts, for equity in accessing health care and improving the socioeconomic, environmental and health conditions of poor populations. This divide affects all cancer types across the entire continuum of care, from prevention to screening, treatment, surveillance, and palliative care [2,8]. Despite comparative achievements attained in cancer control and treatment over the last decades, large inequities remain. Most of these advances have benefited HICs and further expanded the divide

Number of Women (Thousands)

1000 900 800 700 600 500

Incidence, HIC Mortality,HIC

400 300

0 0 0

Incidence, LMIC Mortality, LMIC

200 100 0

Fig. 1. Incidence and mortality of the 10 most prevalent female cancers (all ages) for high and low-middle income countries.

Please cite this article as: del Carmen MG, et al, Global health perspective on gynecologic oncology, Gynecol Oncol (2015), http://dx.doi.org/ 10.1016/j.ygyno.2015.03.009

M.G. del Carmen et al. / Gynecologic Oncology xxx (2015) xxx–xxx

3

Number of Cases (Thousands)

1600 1400 1200 1000 800 600 400 200 0

Breast

Colorectal

Lung

Cervix

Stomach

Uterus

Incidence, 2012

883

276

315

445

152

139

Mortality, 2012

324

163

281

230

41

86

Incidence, 2035

1430

537

640

702

260

228

Mortality, 2035

558

329

586

402

80

154

Figure based on GLOBOCAN 2012 data, Reference # 4. Fig. 2. 2012 and projected 2035 cancer incidence and mortality in women, low-middle income countries.

between rich and poor. In addition, the incidence of preventable cancers, such as cervical, liver and lung cancer has declined significantly in HICs, but there has been little improvement in the incidence and survival of these malignancies in LMICs [6]. Simultaneously, the growing number of non-preventable cancers globally has resulted in a double cancer burden for LMICs.

2.3. Objective In this review, we describe the specific challenges that LMICs face across the cancer spectrum from prevention to screening, to treatment, surveillance/survivorship, and palliation, focusing on gynecologic malignancies and cancers disproportionately affecting women. In addition, we suggest possible opportunities to remedy inequities and close the cancer divide.

3. Primary prevention Although countries with limited health-care budgets often invest more on therapeutic interventions than prevention, data support that prevention is more cost-effective [9]. One-third to one-half of cancer deaths could be avoided through prevention, and early detection/treatment. Taking into account disability and premature deaths, the estimated total annual economic cost of cancer is $US 1.16 trillion [10]. Based on the economic value in 2010 of lost disability adjusted life years (DALYs) and by investment in cancer care and control, savings of $US 131 billion were attainable that year [10]. If value perception of lost income and suffering are factored, estimated global savings of cancer prevention and early detection escalate to a range of $US 543–850 billion [10]. Obstacles to primary and secondary cancer prevention in LMICs include patient-related financial/cultural barriers, limited access to appropriate counseling, poor laboratory quality/control, delays in diagnostics, and limited access to treatment. Successful programs and interventions need to address these socioeconomic and infrastructure factors [9]. Cancer prevention and screening programs should also incorporate adequate epidemiologic data collection and tracking in order to optimize service delivery and outcomes [9]. Tobacco and heavy alcohol use,

obesity, certain infections, and indoor air pollution are preventable and modifiable risk factors [9]. 3.1. Tobacco Globally, tobacco is causal in the development of approximately 15 types of cancer, including cervical cancer, and 20% of cancer-related deaths [11]. Today, 80% of smokers live in LMICs [12]. Approximately 6 million people die annually from tobacco use/exposure, and this figure is expected to be 7.5 million by 2020 [11]. Tobacco use represents a significant economic risk for LMICs, with an estimated $US 500 billion tobacco-related illness and treatment costs, a figure surpassing the total annual health expenditure for all LMICs [11]. If tobacco use continues, the global annual cost between 2020 and 2030 is expected to be $US 1 trillion [12]. The cost of reducing tobacco and harmful alcohol use in all LMIC is $US 2 billion per year, less than $US 0.40/person [12]. Smoking rates for women are lower than for men in LMICs [13]. It is imperative to invest in public health strategies that will continue to lower them [11]. Anti-tobacco policies/interventions present an opportunity for prevention directly impacting mortality [9]. Taxation, restrictions on marketing, labeling, and packaging, and smoking restrictions in public places are effective strategies [9]. Uruguay is the first Latin American country to institute an effective tobacco control campaign by establishing a 100% smoke-free policy in work/public places, increasing the price of cigarettes, and restricting packaging [13]. This has resulted in a decline in smoking rates from 33% in 2005 to 11% in 2011 [13]. Smokeless tobacco causes oral, esophageal and pancreatic cancer. An estimated 89% of smokeless tobacco users are in Southeast Asia. Prevalence among men is estimated to be between 25 and 51%, with equivalent or higher rates reported in women [11,12]. Policies addressing smokeless tobacco prevention and control represent a priority for these countries. 3.2. Physical activity, diet, and obesity The relationship between physical activity, diet, and obesity and several cancers, including endometrial, breast, colorectal, kidney, and gallbladder is well documented. In LMICs, obesity rates are high and

Please cite this article as: del Carmen MG, et al, Global health perspective on gynecologic oncology, Gynecol Oncol (2015), http://dx.doi.org/ 10.1016/j.ygyno.2015.03.009

4

M.G. del Carmen et al. / Gynecologic Oncology xxx (2015) xxx–xxx

rising [14]. In Latin America, 139 million people (23%) are either overweight or obese [15]. Obesity is more prevalent among women than men, with projections estimating that by 2030, 50% of men and 60% of women in Latin America will be overweight or obese [16]. Strategies to address the obesity epidemic include adopting the World Health Organization (WHO) recommendations for food marketing, implementing policies promoting exercise, healthy eating, food labeling/advertisement, requirements, and healthy food choices requirements at schools [16]. At the primary care level, community members and health care workers can be trained to promote healthy eating and physical activity [6]. 3.3. Infection Several cancers are associated with preventable infections, including Kaposi's sarcoma (HIV/AIDS), cervical cancer (HPV), liver cancer (hepatitis B), gastric cancer (H-pylori), bladder cancer (schistosomiasis) and cholangiocarcinoma (clonorchis and opisthorchis). Some of these malignancies can be prevented through vaccination or having a pre-cancerous state amenable to early treatment. Globally, approximately 20% of all cancers are attributable to an infectious etiology [17]. However, in LMICs this proportion is higher with approximately 33% of cancers attributed to infections [17,18]. In 2009, the WHO recommended inclusion of HPV vaccination in national immunization programs, making cervical cancer and other HPV-related disease prevention a public health care priority [19]. As an example of the impact lower vaccination cost has in promoting implementation, the relative success of vaccination against hepatitis B was the decline in cost from a 1982 launch price of $US 100 per dose to $US 0.20 per dose today [20]. Prior to 2011, price/dose for the HPV vaccine in LMICs ranged from $US 30–100. For eligible Latin American countries, efforts from the Pan-American Health Organization (PAHO) Revolving Fund resulted in price reduction to $US 14 per vaccine dose [6]. Through Global Alliance for Vaccines and Immunizations (GAVI) efforts in low-income countries, the vaccine cost is $US 5/dose [20]. HPV vaccination can be promoted through adolescent, sexual/reproductive, and maternal/child health programs. Opportunities include vaccination through schools or religious programs. Peru is one of many countries which has adopted a school-based HPV vaccination program [21]. A prevention-screening program in rural Thailand, is coupling HPV vaccination for the young/adolescent daughter to cervical cancer screening for the mother. In 2011, the government of Rwanda inaugurated a Comprehensive National Cervical Cancer Prevention Program supported by a public–private partnership with industry through which 2 million doses of the HPV vaccine and 250,000 HPV DNA tests were donated and sustainable strategies for on-going vaccination and screening are being developed [22]. This public–private partnership could serve as a model for other LMICs. 3.4. Environmental factors Environmental exposure to carcinogens in the home, workplace and public settings represents a common and preventable cause of cancer worldwide. Poverty is associated with dependence on soil fuels and overcrowded living conditions [6,23–26]. Legislation and policies have reduced exposure risk in HICs [6]. This movement is lagging in LMICs. According to the International Labor Organization, Norway has 97 general and 47 specific laws against occupational health hazards [27]. In contrast, 12 are general laws and 4 are specific ones in India [27]. Worldwide, 3 billion people cook and heat their homes with open fires, using wood, animal dung, and crop waste [9]. Biomass air pollution, resulting from exposure to cooking and tobacco smoke, for example, can result in indoor smoke levels estimated to be 100 fold higher than deemed acceptable [28]. Wood smoke exposure has been associated with lung adenocarcinoma among non-smoking Mexican women

[29]. Wood-smoke exposure may increase the risk of cervical dysplasia and cancer [30,31]. Successful programs, such as Sembrado in Peru, have procured clean stoves to over 92,000 families, reducing home indoor pollution [32]. Further reductions will require continued investments in programs and policies addressing pollution in the home and workplace [6].

4. Secondary prevention Cervical cancer screening has resulted in a 50% reduction in mortality in HICs [33]. Organized screening with appropriate follow-up has been explored by several LMICs with limited success. The economic benefit of early detection and prevention has been shown in a study analyzing total economic cost (medical cost and DALYs averted) for cervical cancer, comparing a “prevention + early detection + treatment” strategy to “treatment” only strategy in LMICs [34]. Three-dose vaccination, plus cervical cytology and colposcopy result in a 55–65% saving [34,35]. Similar cost savings have been documented for breast and colorectal cancer screening [34,35]. The cost of prevention will likely decrease over time, with continued innovation and more efficient strategies. For example, emerging data support two-dose HPV vaccination as effective [6,34,35]. Given that some diseases share risk factors, prevention can result in cumulative savings [6]. Partnering with community health care workers, nurses, and primary care providers can be effective in expanding delivery of secondary prevention services [6]. In Thailand, this community partnership has resulted in successful cervical cancer screening across 29 provinces and in over 500,000 women [36]. In Peru, the Ministry of Health partnered with PAHO and Program for Appropriate Technology in Health (PATH) to expand screening services in rural areas. The program focused on community information and education, screening and diagnostic/treatment services [37]. Intervention teams trained primary care physicians and midwives across 30 primary health care centers to screen via Visual Inspection with Acetic Acid (VIA) and treat with cryotherapy [37]. Through infrastructure shifting, and by developing a regional cancer center in rural Peru, nurses and midwives were trained to integrate breast cancer screening with a previously existing cervical cancer screening program [6]. Patients with breast cancer are referred to the regional cancer center for treatment, allowing them access quality specialty care, without having to travel to urban centers [6]. This program underscores the importance of early evaluation of a breast mass. Stage at the time of diagnosis largely predicts breast cancer cure rates. In most LMICs, 60–70% of breast cancer cases are diagnosed in late stages. Thus, programs like the one in Peru, are of significant potential impact [6]. Innovative strategies, such as HPV-DNA testing, may improve the effectiveness of screening in LMICs. HPV-DNA testing has a higher sensitivity than conventional cytology, allows for longer screening interval, is not observer-dependent, and circumvents the suboptimal quality of cytology analysis [9]. In India, HPV-DNA testing resulted in a decrease in advanced-stage cervical cancer cases and deaths [38]. Another strategy is a “screen and treat” approach where screening is performed with VIA followed by immediate treatment with cryotherapy in screen positive patients [9]. VIA programs may be easier to implement, are less expensive, and do not require highly specialized providers/laboratories for sample collection/processing [39]. Improved access to genetic testing represents another preventive opportunity. BRCA mutation carriers can be educated to modify lifestyle risk factors, and offered surveillance, risk-reducing surgery or chemoprevention. In Latin America, likely as a result of significant Jewish migration from Spain and Portugal, BRCA mutation rates are similar to rates in Europe or the US [40]. In most of these countries, genetic testing is not widely available and strategies incorporating genomic and molecular information into training and practice remain essential in closing the cancer divide [9].

Please cite this article as: del Carmen MG, et al, Global health perspective on gynecologic oncology, Gynecol Oncol (2015), http://dx.doi.org/ 10.1016/j.ygyno.2015.03.009

M.G. del Carmen et al. / Gynecologic Oncology xxx (2015) xxx–xxx

5. Treatment Treatment of gynecologic cancers requires surgery, radiation and systemic therapies, often in combination and requiring multidisciplinary care and sophisticated technology not readily available in LMICs.

5

poor quality of available drugs. In most LMICs, the estimated direct out pocket payment for drug coverage for a patient is 50–90% of the cost of the agent [6]. Drug dilution and counterfeit present further obstacles to delivery of adequate systemic treatment. 5.4. Surveillance/survivorship

5.1. Surgery The choice to treat primarily with surgery in many LMIC often depends on the relative availability of other resources and services. For example, ovarian cancer debulking surgery is often performed, but the chemotherapy needed for adequate treatment is often unavailable. Specialized oncologic surgical training has been shown to reduce morbidity, mortality and cost [41–43]. Although in some LMICs, quality standards and outcomes are achieved in specialized centers, this level of surgical care and appropriate resources may not be available at the community level and in rural areas [9]. The gap has widened as a result of limited access to minimally invasive technology/training in many LMICs [44,45]. Training programs partnering with international institutions/societies, such as those spearheaded by MD Anderson Cancer Center, University of Michigan, and the Society of Gynecologic Oncology of Canada have been successful and should be expanded [46,47]. The Central America Gynecologic Oncology Education Program (CONEP), supported by the International Gynecologic Cancer Society, focuses on resident education and training in the prevention and treatment of gynecologic cancers [48]. The complexity surrounding training, access, and delivery of specialized oncologic surgical care underscores the importance of continuing to develop prevention and screening strategies in LMICs.

As treatment strategies are successfully implemented, programs should also develop appropriate surveillance protocols/services addressing short- and long-treatment-related complications. Initiatives should include screening for recurrences, secondary malignancies, and management of physical/emotional consequences of treatment. Survivorship care may be incorporated into primary care programs [52]. 5.5. Palliative care Given that most cancer patients in LMICs present with advancedstage disease, access to palliative care is essential to closing the cancer divide. Palliative care programs should be designed to provide multidisciplinary care and be inclusive of physicians, nurses, social workers, pharmacists, spiritual counselors, community health workers, and volunteers [53,54]. Although controllable pain is not acceptable in most HICs, many cancer patients in LMICs lack access to pain medication [6]. In most LMICs, access to oral morphine is limited as a result of restrictive policies. Worldwide, 13% of the population lives in HICs and accounts for 94% of morphine consumption [55]. In Sub-Sahara Africa, opioids treat 85,000 patients, with an estimated 1.1 million dying in pain [6,55]. Prescription regulations can be changed through collaboration with ministries of health and educating public health officials, providers and the public [6].

5.2. Radiation therapy 6. Conclusions Effective and safe delivery of radiation therapy requires investment in equipment, space, and staff [6,9]. Over 50% of patients in LMICs lack access to needed radiation therapy [49]. In HICs, technological advances have resulted in adoption of three-dimensional conformal and intensity-modulated radiotherapy, with improved precision in treatment planning and delivery [49]. Cobalt machines account for 7% and 31% of external beam radiation equipment in HICs and LMICs, respectively [49]. Even when equipment is available, the medical and technical expertise required to deliver radiation therapy safely remains a barrier. An estimated 4320 additional megavoltage machines and 43,200 trained professionals to operate them are needed in LMICs [49]. Communication technologies may facilitate mentorship and support of radiotherapy programs in remote regions. The International Atomic Energy Agency (IAEA) provides radiotherapy to LMICs and supports monitoring and provision of radioactive sources. The Latin American Association for Radiation Oncology, partnering with other societies, has established a regional school dedicated to improving training in Latin America. Access to radiation therapy services remains a priority to health ministries and global health efforts in LMICs.

LMICs are disproportionately affected by the challenge of cancer control. Failure to respond to this challenge will have catastrophic human and economic consequences. Efforts focusing on primary and secondary prevention remain central to the global charge to close the cancer divide. Health ministries should be encouraged to invest in cancer registries that include geographic, socioeconomic, and ethnic data. Programs should also focus on the recruitment and training of physicians, nurses, and other healthcare workers [9]. Investing in continued research in cancer epidemiology, health economics, and cost-effectiveness is also imperative. A database of existing programs, technologies and lessons learned should be developed to increase collaboration. The gynecologic oncology community is well positioned to move this agenda forward through partnerships across institutions, our professional societies, and advocacy groups. Conflict of interest statement None of the authors have any conflict of interests.

References 5.3. Systemic therapy Twenty-six of 29 agents for treating the most prevalent and most gynecologic cancers in LMICs are off-patent, including cisplatin, carboplatin, and paclitaxel [6]. But safe drug delivery also requires standardized procedures (for ordering, preparing and administering therapy), management of side effects, clinical/laboratory monitoring, supportive care drugs, and staff training [6]. The global shortage of oncologists presents a major barrier. In Honduras, 20 oncologists serve a population of 8 million, and in Ethiopia, 4 oncologists care for over 80 million people [6,50,51]. Treating more patients worldwide may require training non-oncologist medical professionals, with readily available and appropriate off-site support [2]. Other barriers include high direct cost and

[1] Koplan JP, Bond TC, Merson MH, Reddy KS, Rodriguez MH, Sewankambo NK, Wasserheit JN. Towards a common definition of global health. Lancet 2009;373: 1993–5. [2] Reardon S. A world of chronic disease. Science 2011;333:558–9. [3] World Economic Forum. Global Risks 2010: A Global Risk Network Report. Geneva, Switzerland: World Economic Forum; 2010. [4] Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Cancer Incidence and Mortality Worldwide: GLOBOCAN 2012. http://globocan.iarc.fr. (Accessed January 19, 2015). [5] http://data.worldbank.org/about/country-and-lendinggroups. (Accessed February 07, 2015). [6] Knaul FM, Frenk J, Shulman L. Closing the Cancer Divide: A Blueprint to Expand Access in Low and Middle Income Countries. Boston: Harvard Global Equity Initiative; 2011. [7] Frenk J, Bobadilla JL, Sepúlveda J, Cervantes ML. Health transition in middle-income countries: new challenges for health care. Health Policy Plan 1989;4:29–36.

Please cite this article as: del Carmen MG, et al, Global health perspective on gynecologic oncology, Gynecol Oncol (2015), http://dx.doi.org/ 10.1016/j.ygyno.2015.03.009

6

M.G. del Carmen et al. / Gynecologic Oncology xxx (2015) xxx–xxx

[8] Kanavos P. The rising burden of cancer in the developing world. Ann Oncol 2006;17: 15–23. [9] Goss PE, Lee BL, Badovinac-Crnjevic T, Strasser-Weippl K, Chavarri-Guerra Y, St Louis J, Villarreal-Garza C, Unger-Saldaña K, Ferreyra M, Debiasi M, Liedke PE, et al. Planning cancer control in Latin America and the Caribbean. Lancet Oncol 2013;14: 391–436. [10] Bloom DE, Cafiero ET, Jané-Llopis E. The Global Economic Burden of Noncommunicable Diseases. Geneva: World Economic Forum; 2011. [11] Thun MJ, DeLancey JO, Center MM, Jemal A, Ward EM. The global burden of cancer: priorities for prevention. Carcinogenesis 2010;31:100–10. [12] Shafey O, Eriksen M, Ross H, Mackay J. The Tobacco Atlas. Third edition. American Cancer Society; 2009(http://www.tobaccoatlas.org/downloads/TobaccoAtlas_sm. pdf (Accessed January 19, 2015)). [13] PAHO. CARMEN Meeting Report. http://new.paho.org/carmen/?page_id=11. (Accessed on January 19, 2015). [14] Subramanian S, Perkins JM, Özaltin E, Davey Smith G. Weight of nations: a socioeconomic analysis of women in low- to middle-income countries. Am J Clin Nutr 2011; 93:413–21. [15] PAHO. Strategy for the Prevention and Control of Noncommunicable Diseases. http://new.paho.org/hq/index. php?option=com_content&view=article&id= 7022&Itemid=39541 &lang=en. (Accessed January 20, 2015). [16] Webber L, Kilpi F, Marsh T, Rtveladze K, Brown M, McPherson K. High rates of obesity and non-communicable diseases predicted across Latin America. PLoS One 2012;7:39589–92. [17] Casper C, Sessle E, Phipps W, Yager J, Corey L, Orem J. Uganda program on cancer and infectious diseases. GTF.CCC Working Paper Series, Paper No. 2. Harvard Global Equity Initiative; 2011. [18] Denny L. Cervical cancer in South Africa: an overview of current status and prevention strategies. CME 2010;28:70–3. [19] World Health Organization. Human papillomavirus vaccines. WHO Position Paper, 84. WHO Weekly epidemiological record 10 April 2009: No. 15; 2009. p. 117–32 (http://www.who.int/wer/2009/wer8415.pdf (Accessed January 20, 2015)). [20] Global Alliance for Vaccines and Immunization. GAVI Welcomes Lower Prices for Life-saving Vaccines. Press Release; 6 June, 2011. http://www.gavialliance. org/media_centre/press_releases/vaccine_prices.php. (Accessed January 20, 2015). [21] Penny M, Bartolini R, Mosqueira NR, et al. Strategies to vaccinate against cancer of the cervix: feasibility of a school-based HPV vaccination program in Peru. Vaccine 2011;29:5022–30. [22] CSR Press Release. Rwanda, Merck and QIAGEN Launch Africa's First Comprehensive Cervical Cancer Prevention Program Incorporating Both HPV Vaccination and HPV Testing. CSR Wires. http://www.csrwire.com/press_releases/32078-RwandaMerck-and-QIAGENLaunch-Africa-s-First-Comprehensive-Cervical-Cancer-Prevention-Program-Incorporating-Both-HPV-Vaccination-and-HPV-Testing; April 25, 2011. (Accessed January 20, 2015). [23] Bruce N, Rehfuess E, Mehta S, Hutton G, Smith K. Chapter 42: indoor air pollution. In: Jamison DT, Breman JG, Measham AR, et al, editors. Disease Control Priorities in Developing Countries. 2nd ed. Washington (DC): World Bank; 2006. [24] L. Rosenstock, M. Cullen, M. Fingerhut, Chapter 60: occupational health, in: D.T. Jamison, J.G. Breman, A.R. Measham et al. (Eds.), Disease Control 2007. [25] World Health Organization. Global Status Report on Noncommunicable Diseases 2010. World Health Organization; 2011. [26] Patrinos HA, Psacharopoulos G. Indigenous Peoples and Poverty in Latin America: An Empirical Analysis. Washington, DC: The World Bank; 1994. [27] International Labour Organization (ILO). NATLEX Database. http://www.ilo.org/dyn/ natlex/natlex_browse.home?p_lang=e. (Accessed January 25, 2015). [28] WHO. Indoor Air Pollution and Health. http://www.who.int mediacentre/factsheets/ fs292/en/index.html. (Accessed January 25, 2015). [29] Hernandez-Garduno E, Brauer M, Perez-Neria J, Vedal S. Wood smoke exposure and lung adenocarcinoma in non-smoking Mexican women. Int J Tuberc Lung Dis 2004; 8:377–83. [30] Ferrera A, Velema JP, Figueroa M, et al. Co-factors related to the causal relationship between human papillomavirus and invasive cervical cancer in Honduras. Int J Epidemiol 2000;29:817–25.

[31] Sierra-Torres CH, Arboleda-Moreno YY, Orejuela-Aristizabal L. Exposure to wood smoke, HPV infection, and genetic susceptibility for cervical neoplasia among women in Colombia. Environ Mol Mutagen 2006;47:553–61. [32] Bodereau PN. Peruvian highlands, fume-free. Science 2011;334:157–65. [33] Kitchner HC, Castle PE, Cox JT. Achievements and limitations of cervical cytology screening. Vaccine 2006;24:63–70. [34] Seinfeld J, Beltran A, Morocho E. Background paper: cost–benefit analysis of cancer care and control. The Case of Cervical and Colorectal Cancer in LMIC; 2011. [35] Groot MT, Baltussen R, Uyl-de Groot CA, Anderson BO, Hortobágyi GN. Costs and health effects of breast cancer interventions in epidemiologically different regions of Africa, North America, and Asia. Breast J 2006;12:81–8. [36] http://www.nytimes.com/2011/09/27/health/27cancer.html. (accessed January 29, 2015). [37] Luciani S, Winkler J. Cervical Cancer Prevention in Peru: Lessons Learned From the TATI Demonstration Project. Pan-American Health Organization; 2006(http:// www.paho.org/english/ad/dpc/nc/pcc-cc-tati-rpt.pdf (Accessed January 30, 2015)). [38] Sankaranarayanan R, Nene BM, Shastri SS, et al. HPV screening for cervical cancer in rural India. N Engl J Med 2009;360:1385–94. [39] PAHO. Situation Analysis, Strategies for Cervical Cancer Screening With Visual Inspection With Acetic Acid and Treatment With Cryotherapy in Latin America and the Caribbean. Washington, DC: Pan American Health Organization; 2012. [40] Jara L, Ampuero S, Santibanez E, et al. BRCA1 and BRCA2 mutations in a South American population. Cancer Genet Cytogenet 2006;166:36–45. [41] Farjah F, Flum DR, Varghese Jr TK, Symons RG, Wood DE. Surgeon specialty and longterm survival after pulmonary resection for lung cancer. Ann Thorac Surg 2009;87: 995–1004. [42] Kingsmore D, Hole D, Gillis C. Why does specialist treatment of breast cancer improve survival? The role of surgical management. Br J Cancer 2004;90:1920–5. [43] Barbas AS, Turley RS, Mantyh CR, Migaly J. Effect of surgeon specialization on longterm survival following colon cancer resection at an NCI-designated cancer center. J Surg Oncol 2012;106:219–23. [44] Verdecchia A, Mariotto A, Gatta G, Bustamante-Teixeira MT, Ajiki W. Comparison of stomach cancer incidence and survival in four continents. Eur J Cancer 2003;39: 1603–9. [45] Dall'Oglio MF, Coelho R, Lopes R, et al. Signifi cant heterogeneity in terms of diagnosis and treatment of renal cell carcinoma at a private and public hospital in Brazil. Int Braz J Urol 2011;37:584–90. [46] Keshtgar M, Zaknun JJ, Sabih D, et al. Implementing sentinel lymph node biopsy programs in developing countries: challenges and opportunities. World J Surg 2011;35: 1159–68. [47] Pareja R, Nick AM, Schmeler KM, Frumovitz M, Soliman PT, Buitrago CA, Borrero M, Angel G, Reis RD, Ramirez PT. Quality of laparoscopic radical hysterectomy in developing countries: a comparison of surgical and oncologic outcomes between a comprehensive cancer center in the United States and a cancer center in Colombia. Gynecol Oncol 2012;125:326–9. [48] Schmeler KM, Ramirez PT, Reyes-Martinez CA, Chernofsky MR, del Carmen MG, Diaz-Montes TP, Padilla L, Tejada-Berges T, Tarraza H, Bermudez A, Trimble EL. The Central America Gynecologic Oncology Education Program (CONEP): improving gynecologic oncology education and training on a global scale. Gynecol Oncol 2013; 129:445–7. [49] Zubizarreta EH, Fidarova E, Healy B, Rosenblatt E. Need for radiotherapy in low and middle income countries: the silent crisis continues. Clin Oncol 2015;27:107–14. [50] American Society of Clinical Oncology/Health Volunteers Overseas. International Cancer Corps Needs Assessment Reports on Honduras; 2008. [51] The Max Foundation. Homepage. Home Page. http://www.themaxfoundation.org/; 2011. (Accessed February 2, 2015). [52] Institute of Medicine. Implementing Cancer Survivorship Care Planning. Washington, D.C.: National Academies Press; 2007 [53] Stjernswärd J, Foley KM, Ferris FD. The public health strategy for palliative care. J Pain Symptom Manage 2007;33:486–93. [54] World Health Organization. Palliative Care. World Health Organization; 2011(http:// www.who.int/cancer/palliative/en/ (Accessed February 2, 2015)). [55] Liberman J, O'Brien M, Hall W, Hill D. Ending inequities in access to effective pain relief? Lancet 2010;376(9744):856–9.

Please cite this article as: del Carmen MG, et al, Global health perspective on gynecologic oncology, Gynecol Oncol (2015), http://dx.doi.org/ 10.1016/j.ygyno.2015.03.009