In light of continued innovation in cancer immunotherapy regimens and surgical management, no studies currently exist assessing the effect of these advances on global disparities in lip and oral cavity cancer disease burden. The purpose of this study is to characterize longitudinal trends in disease burden caused by lip and oral cavity cancers globally.
Materials and Methods
This retrospective, longitudinal cohort study extracted data on lip and oral cavity cancer disease burden from The Global Health Data Exchange for 1990-2017. The primary predictor variable was country human development index (HDI). The primary outcome variable was disease burden, measured by age-standardized disability-adjusted life years (DALYs) per 100,000 population, listed for each individual country. Additional variables assessed include country-level data on alcohol consumption and tobacco smoking. Concentration indices were also calculated. Mann-Whitney U and Kruskal-Wallis one-way analysis of variance tests with Bonferroni correction were utilized with a significance threshold of 0.008.
A total of 185 countries met inclusion criteria. Global age-standardized DALYs increased from 44.5 ± 35.7 to 51.1 ± 41.1 from 1990 to 2017. High HDI and medium HDI countries showed a +37.6% and +22.4% median increase in DALYs, respectively, which is significantly greater than very-high HDI (+3.8%) and low HDI countries (−0.5%) ( P < .001). The concentration index for lip and oral cavity cancer became increasingly negative from −0.064 to −0.077 from 1990 to 2015. In 2017, disease burden was concentrated in South Asia and Eastern Europe.
High and medium HDI countries experienced a disproportionate growth in lip and oral cavity cancer disease burden. These findings may have resulted from increased life expectancy among these countries. Global and public health policy initiatives should focus on understanding the mechanisms driving these disparities with the goal of reducing disease burden globally.
Cancers of the lip and oral cavity represent some of the most common malignancies worldwide. Recent studies have estimated a dramatic increase in the absolute number of lip and oral cavity cancers globally, from approximately 186,000 cases in 1990 to 389,000 cases by 2017 a 109% increase. Countries representing the lowest-to-middle socioeconomic status accounted for most of the increased incidence in lip and oral cavity cancers, with cases concentrating in various subregions such as Australasia, Southeast Asia, and Melanesia. Global estimates of deaths from lip and oral cavity cancer have risen 98.7% over the same time period. Despite efforts to characterize longitudinal trends in lip and oral cavity cancer incidence and mortality, no studies to date have attempted to exclusively assess the impact of its disease burden on nations globally.
Although numerous advances have been made in the treatment and management of malignancies throughout the body, such as breast cancer and lung cancer, the morbidity and mortality of lip and oral cavity cancers has steadily increased. Recently, the advent of immunotherapy and targeted cancer therapeutics make possible new avenues of treatment. However, the exorbitant cost of these drugs limits access for patients from low- and middle-income countries. Pembrolizumab, now first-line therapy for metastatic and unresectable head and neck cancers, can cost upward of $US8,762 per 200 mg dose. , As new regimens improve survival, the considerable cost associated with these treatments may have a substantial impact on the distribution of disease burden across differing socioeconomic populations. Further data are needed to characterize if global disparities in lip and oral cavity cancer disease burden have widened (or narrowed) in light of these advances.
The burden of disease, as opposed to measuring incidence and mortality, provides a more comprehensive understanding of the relative impact of a disease on the psychosocial, physical, emotional, and financial well-being of populations. Understanding and quantifying this principle on a global scale, defined as the global burden of disease (GBD), is critical in informing policy decisions on the allocation of limited health care resources globally. Metrics aimed at quantifying the GBD, such as disability-adjusted life years (DALYs), help policy makers categorize geographical and societal disparities in health services and interventions. Furthermore, characterizing trends in disease burden allows policy makers to assess the impact of global health initiatives on alleviating disability and death.
The purpose of this study was to characterize long-term trends in lip and oral cavity cancer disease burden on a global scale. Specifically, the authors aimed to 1) examine longitudinal trends in lip and oral cavity cancer GBD from 1990 to 2017, 2) evaluate the GBD of lip and oral cavity cancer stratifying by country socioeconomic status, 3) assess the equality (or inequality) of the distribution of lip and oral cavity cancer disease burden worldwide, and 4) compare trends in disease burden with global trends in alcohol consumption and tobacco smoking. We hypothesize that the GBD of lip and oral cavity cancer has increased from 1990 to 2017, with the burden disproportionately impacting developing and economically maturing countries.
Materials and Methods
Study Design and Data Source
This retrospective, longitudinal cohort study analyzed country-specific population data on lip and oral cancer disease burden extracted from The Global Health Data Exchange (GHDx) from 1990 to 2017. Specifically, this study consists of lip and oral cavity GBD data from individual countries as recorded in the GHDx. The GHDx, supported by the Institute for Health Metrics and Evaluation (IHME), is a centralized database of global health-related statistics and demographic information focusing on improving the health of populations around the world. This study builds on previously published methods for analyzing trends in global burden of disease. For countries to be included in this study, information regarding DALYs for lip and oral cavity cancer must be recorded in the GHDx from 1990 to 2017. Countries were excluded from analysis if they were listed as a territory under the GHDx. This study did not require institutional review board approval as these data are publicly available and no informed consent was required.
The primary predictor variable was country human development index (HDI). The HDI is a composite statistic measuring the developmental progress of a country. Each country is assigned a single HDI value, which is comprised of the following 4 measures: 1) life expectancy; 2) expected years of schooling; 3) mean years of schooling for adults; and 4) gross national income per capita (adjusted for inflation and intercountry price differences). The authors extracted HDI values for each country as listed in the 2019 Human Development Report by the United Nation's Development Program. Countries were then subcategorized into 4 groups based on their respective HDI values: 1) very-high human development index (VHHDI) (HDI: 1.000-0.800); 2) high human development index (HHDI) (HDI: 0.799-0.700); and 3) medium human development index (MHDI) (HDI: 0.699-0.550), and low human development index (LHDI) (HDI: 0.549-0.000).
The primary outcome variable was lip and oral cancer disease burden, measured by age-standardized DALYs (per 100,000 population) per country. DALYs were created in a joint effort by the World Health Organization (WHO) and the World Bank to formulate a single measure of disease burden on a population. DALYs are calculated based on the following formula: 1) years-of-life lost due to disability added to, 2) years of life lost due to premature mortality (YLL), and 3) age-adjusted. Years-of-life lost due to disability is calculated by multiplying the number of years lived with a disability by a value known as a disability weight, which reflects the severity of a disease and its impact on one's quality-of-life. , The disability weight is measured on a scale from 0 (perfect health) to 1 (equal to death). Estimates of the disability weight for oral cancer can range from 0.049 to 0.540, depending on the stage and location of the lesion at the initial diagnosis. Finally, YLL is a measurement of the quantity of years lost due to premature mortality.
The GHDx defines lip and oral cavity cancers as primary, malignant neoplasms diagnosed at the following anatomical locations (ICD-10-CM): C00 (lip), C01 (base of tongue), C02 (other and unspecified parts of tongue), C03 (gums), C04 (floor of mouth), C05 (hard and soft palate), C06 (other and unspecified parts of mouth), C07 (parotid gland), C08.0 (submandibular gland), C08.1 (sublingual gland), C08.9 (major salivary gland, unspecified), and Z85.81 (personal history of malignant neoplasm of lip, oral cavity, and pharynx).
Concentration indices (CI) were calculated for 1990, 1995, 2000, 2005, 2010, and 2015 to assess longitudinal trends in the inequality (or equality) of lip and oral cavity cancer disease burden globally. CI values can range between +1 and -1. A negative value would indicate the burden of lip and oral cavity cancer is disproportionately concentrated among less socioeconomically developed countries, whereas a positive value would indicate that the disease burden of lip and oral cavity cancer is disproportionately concentrated among more socioeconomically developed countries. A value of zero would indicate equal burden of disease across countries and socioeconomic status.
Additional outcome variables assessed include alcohol per capita consumption (ages 15+) by country and rates of tobacco smoking (percentage of population ages 15+) by country. Country-level data on alcohol consumption were extracted from the WHO Global Health Observatory Data Repository for the years 2000, 2005, 2010, and 2015 to analyze trends between rates of alcohol use and global burden of lip and oral cavity cancer across HDI subgroups. Country-level data on the prevalence of tobacco smoking (not including chewing or smokeless tobacco) was extracted from the 2015 WHO Global Report on Trends in Prevalence of Tobacco Smoking for the years 2000, 2005, 2010, and 2015 to characterize the relationship between rates of tobacco use and global burden of lip and oral cavity cancer across HDI subgroups.