Background
Lymphoma, comprising Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL), is one of the common cancers worldwide. In 2016, the incident cases and death number were 73,000 and 28,700 due to HL globally, and 461,000 and 239,600 due to NHL, respectively [
1]. Of note was that the mortality rates of HL and NHL decrease during the period of 2006–2016 [
2]. According to the statistics of GLOBOCAN 2018 [
3], lymphoma accounted for 3.2% of the 18.1 million new cancer cases (0.4% due to HL and 2.8% due to NHL) and 2.9% of the 9.6 million cancer deaths worldwide in 2018 (0.3% due to HL and 2.6% due to NHL). Compared with the statistics of GLOBOCAN 2012 [
4], both new cases and deaths associated with lymphoma increased in 2018.
The disease burden of lymphoid neoplasms has been rising in China over the last decade [
2]. Based on the data from the National Central Cancer Registry of China [
5], it was estimated that lymphoma and myeloma accounted for 2.1% (88,200 new cases) of all new cancer cases and 1.9% (52,100 deaths) of all cancer deaths in 2015. A recent study [
6] showed that the mortality rates of lymphoma and myeloma increased annually by 4.5% during the period 2004–2016. However, accurate epidemiologic information of lymphoma based on national population cannot be available in China. Ultimately, an understanding of trends will help to direct future studies on strategy for disease control and prevention. Therefore, this analysis aimed to determine the incidence, mortality, and prevalence of lymphoma in 2016 and analyze temporal trends from 2006 to 2016 in China.
Discussion
The present study was the most comprehensive evaluation of the large and ever-growing burden of lymphoma in China. The standardized methods for estimates of lymphoma metrics used in the GBD study made it possible to compare a global level with that in China. We determined the disease burden of lymphoma in China. Over 260,000 Chinese people suffered from lymphoma in 2016, meaning that there were about 20 lymphoma patients per 100,000 population in China.
The patterns of burden of HL and NHL varied by age and sex in our study. Similar to most cancers in China, there was a strong trend for higher incidence and mortality of both HL and NHL in older individuals. Notably, lymphoma has been proven to be the third most common cancer type in males and females aged 0–14 years [
10]. Male predominance of incidence and mortality was seen in all age groups for both HL and NHL, which could be explained partly by some risk factors such as smoking and infections [
11]. In addition, our study highlights important variations in the geographical differences across provinces. Higher incidence rates were seen in those provinces with high SDI, and higher mortality rates were observed in those provinces with low SDI, which was mainly due to an imbalance in socioeconomic development. Based on these disparities in disease burden, different strategies for disease prevention and control should be employed when health policy is made in the future.
Although the ASIR of HL increased in China while decreased globally (6.98% vs. − 6.80%) between 2006 and 2016, the ASMR declined more rapidly in China than globally (− 35.67% vs. − 22.40%), indicating that more DALYs were saved in China. This rapid declining trend of ASMR could be associated with continuously improving diagnosis and treatment techniques. Numerous treatment options have emerged for HL, especially in the last five decades. Until now, the majority of lymphoma patients can be cured with a conventional combination of chemotherapy and radiotherapy. Salvage therapy represented by stem cell transplantation and novel agents such as brentuximab vedotin [
12] and immune checkpoint inhibitors [
13] may give the second chance of cure for those with relapsed or refractory disease.
The burden of NHL in China rose more significantly than globally. The change of age-standardized DALYs per 100,000 population for NHL from 2006 to 2016 was 9.18% in China and 1.4% worldwide. The prognosis of B cell NHL, the most common type of NHL, was improved by immunochemotherapy based on rituximab and anthracyclines [
14]. A study from Surveillance, Epidemiology, and End Results database demonstrated that there were 279,704 cumulative life years saved and an incremental economic gain of $16.52 billion after the introduction of rituximab into clinical practice [
15]. However, the protection offered by health insurance was often incomplete [
16]. Many patients with NHL, especially in less-developed provinces in China, could not afford expensive anticancer agents such as rituximab. To solve this problem, health insurance reform with an aim of wider coverage was performed in China since 2009 [
17], of which both equality and efficacy were taken into account [
18]. Our findings highlight the need to address universal health coverage in China, and further study to compare the cost-effectiveness between pre- and post-health insurance reform should be executed.
There are marked differences in the epidemiological characteristics of lymphoma between western and eastern countries [
19]. In the USA, HL incidence had a peak at the age group of 21–30 years, regardless of race [
20]. Differently, our study showed HL incidence had an upward trend with age and had a peak at the age group of 70–74 years in China. Different temporal trend patterns were also observed. In the USA, incidence rates of NHL almost doubled during 1974–2009, increasing rapidly through the early 1990s, followed by more gradual increases and stable rates since the early 2000s [
21]. However, the incidence rates of both HL and NHL have been increasing substantially in Asian countries such as Japan [
22] and Korea [
23]. Consistent with Asian reports, our study showed that the incidence of HL and NHL in China increased without any plateau from 2006 to 2016. The dramatic increase in lymphoma burden may be interpreted partly by improvements in diagnostic procedures [
24] and changes of lifestyle [
25,
26], but much of this trend was largely unexplained and warrants investigation.
Although the etiology of lymphoma is not yet completely understood, there are a few well-established risk factors of lymphoma such as aging, family history, and various infections. Aging is found to be the leading risk factor of lymphoma with higher incidence and mortality rates in older individuals. An upward trend with age in the ASIR and ASMR for both HL and NHL was observed (Fig.
1). The Epstein-Barr virus (EBV) and hepatitis B virus (HBV) were endemic with the seroprevalence of 90% [
27] and 7.2% [
28] in China, which may play a crucial role in the disease burden of lymphoma [
11]. A pooled study [
29] based on three prospective cohorts from China and Singapore confirmed that an increased risk of NHL was related to EBV infection (odds ratio (OR) = 2.17) and HBV infection (OR = 2.16). Similarly, the burden of HL could be attributable to EBV infection with the population-attributable fractions of 56.0% in China [
30].
The interpretation of our study has several limitations. First, all the general limitations described by the GBD collaboration group [
2,
7‐
9] apply to the present study, because the data for this study were from GBD 2016. Second, the incidence and mortality rates of HL estimated using the standard GBD methodology were very low, especially in province levels, leading to the inaccuracy of estimated results. Third, population growth and socioeconomic structures should also be considered in a cautious interpretation of the change trends of lymphoma burden in China.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.