Global health issues in pediatric oncology

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How does the epidemiology of childhood cancer vary in different geographic regions of the world?

Variation in the epidemiology of childhood cancer worldwide is largely influenced by the impact of infection-associated malignancies ( Figure 28.1 ). Although acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy observed in most geographic regions of the world, equatorial sub-Saharan Africa has long been characterized by the uniquely high incidence of Burkitt lymphoma in children. Although Epstein-Barr virus (EBV) was originally discovered from a tumor sample taken from a Ugandan child with Burkitt lymphoma in the 1960s, the geographic distribution of endemic Burkitt lymphoma is geographically linked with holoendemic prevalence of plasmodium falciparum infection rather than EBV-specific factors. Additional epidemiological drivers of unique distinctions in childhood cancer patterns in sub-Saharan Africa include the disproportionate burden of human immunodeficiency virus (HIV) infection and the high prevalence of human herpesvirus-8 (HHV-8), which is the causative agent of Kaposi sarcoma (KS). Both of these factors contribute to the remarkably high incidence of KS in children in eastern, central, and southern Africa—regions of the continent with the highest rates of HHV-8 infection—where KS is ranked among the five most common childhood cancers overall.

Although EBV is equally ubiquitous in worldwide prevalence, there are geographic distinctions in the distribution of several EBV-related malignancies. EBV-related Burkitt lymphoma and Hodgkin lymphoma are more prominent in low- and middle-income countries (LMIC); however, the explanation for this phenomenon remains uncertain. Although rare in comparison, the distinct spectrum of EBV-related T- and natural killer (NK)-cell lymphomas and lymphoproliferative disorders (LPD) occur at disproportionately higher rates in East Asia, Mexico, and Central and South America. This heterogeneous group of lymphoid neoplasms includes the extranodal NK/T-cell lymphoma nasal type, the systemic EBV ⁺ T-cell lymphoma of childhood, aggressive NK-cell leukemia, hydroa vacciniforme-like LPD, severe mosquito bite allergy, systemic T/NK-cell chronic active EBV, and EBV-associated hemophagocytic lymphohistiocytosis (HLH). Ultimately, the impact of infection-associated malignancies is more profound in adult oncology, highlighted by extreme numbers of patients with Helicobacter pylori -associated gastric cancer, human papillomavirus-associated cervical carcinoma, hepatitis B/C virus-associated hepatocellular carcinoma, and EBV-associated nasopharyngeal carcinoma. Nevertheless, notable variations in the epidemiology of childhood cancer are also attributable to the relationship between infection and malignancy ( Table 28.1 ).

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What are some of the factors contributing to the glaring disparities in curative outcomes for children with cancer in LMIC?

Globally, greater than 400,000 children and adolescents are estimated to develop cancer each year. ¹¹ More than 85% of these patients live in LMIC, where the estimated survival is less than 30%, contrasting starkly with the 80% survival achieved for the approximately 45,000 children diagnosed with cancer in high-income countries (HIC). Although innumerable factors contribute to this unacceptable disparity in survival, the relationship between poverty and poor survival is inseparable. One of the biggest limitations is the failure to recognize and diagnose cancer in children at all, with an estimated 50% of children who develop cancer in LMIC never even being diagnosed, compared with an estimated 6% in HIC ( Figure 28.2 ). Challenges along the cancer diagnosis and treatment spectrum include the following:

• General lack of access to both primary care and specialized health care; societal perception of cancer as incurable (including among health care workers)

• Late clinical presentation by the time a diagnosis is achieved

• Lack of diagnostic and therapeutic technologies

• Lack of access to essential anticancer and other supportive care medications

• Lack of financial cushion for families to support themselves through the time-intense commitment to complete therapy

• Relative emphasis on priorities of public health leadership within given countries

• Presence of severe comorbidities such as malnutrition or infection

• Inherent challenges in delivering anticancer treatment and supportive care amid severe limitations in medical resources

Whether basic daily needs or sophisticated technological advances, severe societal limitations for masses of people marginalized by extreme poverty contribute to the dismal survival rates for children with cancer living in LMIC.

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