Global, regional and national incidence, mortality and disability‐adjusted life‐years of skin cancers and trend analysis from 1990 to 2019: An analysis of the Global Burden of Disease Study 2019

Abstract Background Information about global and local epidemiology and trends of skin cancers is limited, which increases the difficulty of cutaneous cancer control. Methods To estimate the global spatial patterns and temporal trends of skin cancer burden. Based on the GBD 2019, we collected and analyzed numbers and age‐standardized rates (ASR) of skin cancer incidence, disability‐adjusted life years (DALYs) and mortality (ASIR, ASDR, and ASMR) in 204 countries from 1990 through 2019 were estimated by age, sex, subtype (malignant skin melanoma [MSM], squamous‐cell carcinoma [SCC], and basal‐cell carcinoma [BCC]), Socio‐demographic Index (SDI), region, and country. Temporal trends in ASR were also analyzed using estimated annual percentage change. Results Globally, in 2019, there were 4.0 million BCC, 2.4 million SCC, and 0.3 million MSM. There were approximately 62.8 thousand deaths and 1.7 million DALYs due to MSM, and 56.1 thousand deaths and 1.2 million DALYs were attributed to SCC, respectively. The men had higher ASR of skin cancer burden than women. The age‐specific rates of global skin cancer burden were higher in the older adults, increasing trends observed from 55 years old. Geographically, the numbers and ASR of skin cancers varied greatly across countries, with the largest burden of ASIR in high SDI regions. However, an unexpected increase was observed in some regions from 1990 to 2019, such as East Asia, and Sub‐Saharan Africa. Although there was a slight decrease of the ASMR and ASDR, the global ASIR of MSM dramatically increased, 1990–2019. Also, there was a remarkable increase in ASR of BCC and SCC burden. Conclusions Skin cancer remains a major global public health threat. Reducing morbidity and mortality strategies such as primary and secondary prevention should be reconsidered, especially in the most prevalent and unexpected increased regions, especially for those areas with the greatest proportions of their population over age 55.


| Data source
The burden of disability associated with a disease or disorder can be measured in units called disability-adjusted life years (DALYs). DALYs represent the total number of years lost to illness, disability, or premature death within a given population. Data on annual incident cases, death numbers, DALYs numbers, and the corresponding age-standardized incidence rate (ASIR), age-standardized DALY rate (ASDR) and agestandardized mortality rate (ASMR) of skin cancer from 1990 to 2019 were collected at the global, regional, and national levels, by age, sex, and subtypes via the Global Health Data Exchange (GHDx) query tool (http://ghdx.healt hdata.org/ gbd-resul ts-tool). Geographically, the world was classified into 21 regions. Moreover, 204 countries and territories were grouped into five Socio-demographic Index (SDI) groups, including low, low-middle, middle, high-middle, and high SDI. The general methods for the GBD 2017 have been detailed in previous studies. 5,18,19 In brief, skin cancer was defined according to the International Classification of Diseases (ICD-10: C43-C43.9, D03-D03.9, D22-D23.9, D48.5, and ICD-9: 172-172.9 for MSM; ICD-10: C44-C44.9, D04-D04.9, D49.2, and ICD-9: 173-173.9, 222.4, 232-232.9, 238.2 for NMSCs), and the GBD 2017 categorized them into two cancer groups: MSM and NMSCs (composed of BCC and SCC). 5,18,20 The Cause of Death Ensemble Model (CODEm) was used to generate cause-specific mortality and years of life lost (YLLs) estimates, and DisMod-MR 2.1 was used to estimate disease burden (incidence, and years lived with disability [YLDs]). All data above and the corresponding 95% uncertainty intervals (UIs) were estimated based on database of cancer registries, the published literature, surveillance data, census data, and others data sources, by location, sex, age group. 5,18,19 DALYs were calculated as the sum of cause-specific mortality, YLLs and YLDs. 21

| Statistical analyses
We chose the estimated annual percentage change (EAPC) in ASIR, ASMR, and ASDR to quantify the temporal trends of skin cancer burden worldwide, from 1990 to 2019. The detailed methods of EAPC have been previously reported. 19,22,23 Briefly, a regression line model was applied to describe the K E Y W O R D S basal-cell carcinoma, disability-adjusted life-years, global burden of disease, incidence, malignant skin melanoma, mortality, skin cancers, squamous-cell carcinoma annual percentage changes in ASR, fitting the natural logarithm of the rates i.e., y = α + βx + ɛ, where y = ln(ASR), and x = calendar year. The EAPC in ASR was estimated as 100 × (exp(β)-1), and captured 95% confidence interval (CI). 23 All statistics were analyzed via R program (R core team version 3.5.3, Vienna, Austria). A two-sided p value <0.05 was regarded as statistically significant.

| Global incidence, mortality and DALYs of skin cancers in 2019
Globally, in 2019, for all ages and both sexes combined, the sheer numbers of three incident skin cancers were 4.0 million (95% UI 3.5 to 4.5) BCC, 2.4 million (95% UI 2.1 to 2.7) SCC, and 0.3 million (95% UI 0.2 to 0.3) MSM. There were approximately 62.8 thousand (95% UI 46.3 to 71.0) deaths and 1.7 million (95% UI 1.3 to 2.0) DALYs were due to MSM, and 56.1 thousand (95% UI 50.4 to 59.8) deaths and 1.2 million (95% UI 1.1 to 1.3) DALYs were attributed to SCC. The numbers and ASRs in incidence, mortality, and burden of three skin cancers in men were higher than those in women (Table 1). Figure 1 showed age-specific rates of global burden of skin cancers in 2019. The rates of global skin cancer burden were higher in the older adults, increasing trends observed from 55 years old in all the subtypes.

| Regional-and national-level incidence, mortality and burden of skin cancers in 2019
The numbers and corresponding ASR of incidence, DALYs and deaths of MSM were highest in high SDI regions in 2019. For SCC, the highest number of incident cases and ASIR also occurred in high SDI regions, while the greatest numbers and corresponding ASR of DALYs and deaths were in middle SDI regions. The highest numbers, ASIR and ASDR of BCC were observed in high SDI regions (Table 1). Geographically, the ASR of skin cancers varied markedly in 2019 ( Table 1). The highest ASR of MSM was all found in Australasia. Regarding NMSCs, the largest incident number and ASIR of SCC were found to be in Highincome North America, and the highest numbers of DALYs and deaths were in East Asia, while Southern Sub-Saharan Africa showed the greatest ASDR and ASMR. The greatest ASIR and ASDR of BCC were both observed in Highincome North America. Figure 2A, Figure 3A and Figure 4A showed the variations in ASIR, ASDR, and ASMR of three skin cancers in 204 countries and territories in 2019. For instance, the ASIR of MSM ranged from 0. 22

| Trends of the three skin cancers burden from 1990 to 2019
The ASIR of the three skin cancers significantly increased in most of the SDI and 21 geographical regions, with the largest increase observed in East Asia for MSM and SCC, and high-income North America for BCC (Table 1, Figure 2B, Figure 3B, Figure 4B). The changes in ASDR and ASMR of the three skin cancers were heterogeneous across the regions. For MSM, the highest increase in ASDR and ASMR was observed in Eastern Europe and Central Latin America, respectively. For SCC, the greatest increase was observed in Central Asia, next was East Asia and Sub-Saharan Africa. The ASDR of BCC in high-income North America and East Asia showed the most pronounced increase.
There were considerable variations in the changes in ASR of the three skin cancers from 1990 to 2019 at the national level ( Figure 2B, Figure 3B, Figure 4B). The ASIR of MSM was significantly increased in 167 countries and territories with the greatest one in South Korea (EAPC: 5.87, 95% CI: 5.40 to 6.34). While the ASIR of SCC also had a change in all 204 countries and territories (184 of which were increased), with the EAPC ranging from −1. 36      In this study, we comprehensively analyzed the spatial and temporal trends in incidence, mortality and DALYs of skin cancers at the global, regional, and national level, by age, sex and subtype from 1990 to 2019. Although in some regions and countries, the primary and secondary prevention for BCC, such as UVR protection and early self-detection, have the potential to substantially reduce morbidity and health care costs of BCC in recent years, 8,10,24,25 the global burden of BCC continues to grow in ASIR and ASDR. The global aging of the population has become more serious, which is probably the main reason for an increase in ASIR of BCC worldwide. 12 Moreover, an unexpected and significant increase of ASIR due to BCC was observed in East Asia, in which the efforts for BCC prevention and screening programs should be made to reduce the healthcare costs and morbidity. 26 In contrast to other regions in the world, the SCC mortality and DALYs in Southern Sub-Saharan Africa in 2019, however, remained disproportionately high in comparison with incidence. Many patients with SCC and other cancers in sub-Saharan Africa, presented with latestage disease, are thought to be associated with limited resources, lower socio-economic status, poor disease awareness, difficulty detecting pigmented lesions in darker skin, little to no access to early detection and/or timely treatment, 27,28 a high burden of immunosuppression due to the HIV/AIDS epidemic in sub-Saharan Africa and other sociocultural factors. [29][30][31] Globally, in both sexes, there was a gradual decline in ASMR and ASDR of MSM from 1990 to 2019. The significant decrease in mortality and DALYs of MSM between 1990 and 2019 may be due in part to preventive measures such as self-examination, public education, and development of new multiple treatment options in past decades, especially in some developed countries with high prevalence and incidence. 8,10,25 However, there are still high incidence and great age-standardized DALYs burdens caused by skin cancers in the high SDI regions or those developed countries, such as America, Australasia and Norway, in which the light-skinned population accounts for a large proportion of the national population. The association of skin cancer with skin color is a significant etiologic factor except for UVR exposure. 2,6,32 Skin cancer is less common in darkly pigmented people than in light-skinned Caucasians, the former comes with more epidermal melanin to protect against UVR damage in human skin. 2,28 Moreover, we observed geographic variations in the incidence of skin cancers via the global heat map, with a higher incidence trends far away from the equator. Previous studies demonstrated that there was a significant association F I G U R E 2 The global distribution of age-standardized rates (ASR) of malignant skin melanoma incidence, disability-adjusted life years (DALYs), and mortality for both sexes in 2019 (A, the left column), and the corresponding EAPCs of ASR from 1990 to 2019 (B, the right column). Abbreviations: ASIR, age-standardized incidence rate; ASDR, age-standardized DALY rate; ASMR, age-standardized mortality rate F I G U R E 3 The global distribution of age-standardized rates (ASR) of squamous-cell carcinoma incidence, disability-adjusted life years (DALYs), and mortality for both sexes in 2019 (A, the left column), and the corresponding EAPCs of ASR from 1990 to 2019 (B, the right column). Abbreviations: ASIR, age-standardized incidence rate; ASDR, age-standardized DALY rate; ASMR, age-standardized mortality rate F I G U R E 4 The global distribution of age-standardized rates (ASR) of basal-cell carcinoma incidence, disability-adjusted life years (DALYs), and mortality for both sexes in 2019 (A, the left column), and the corresponding EAPCs of ASR from 1990 to 2019 (B, the right column). Abbreviations: ASIR, age-standardized incidence rate; ASDR, age-standardized DALY rate; ASMR, age-standardized mortality rate