Epidemiology of classical Hodgkin lymphoma and its association with Epstein Barr virus in Northern China

Abstract

Background: The incidence of classical Hodgkin lymphoma (cHL) and its association with Epstein-Barr virus (EBV) varies significantly with age, sex, ethnicity and geographic location. This is the first report on epidemiological features of cHL patients from Northern regions of China. These features are compared to data from a previously published Dutch cHL population.

Methodology/principal findings: 157 cHL patients diagnosed between 1997 and 2008 in the North of China were included after histopathological re-evaluation. The Dutch population-based cohort consisted of 515 cHL patients diagnosed between 1987 and 2000. EBV status was determined by in situ hybridization of EBV- encoded small RNAs. In the Chinese population, tumor cells of 39% of the cHL patients were EBV+ and this was significantly associated with male sex, mixed cellularity subtype and young age (<20 y). The median age of the Chinese patients was 9 years younger than that of the Dutch patients (28 y vs. 37 y). In addition, the age distribution between the two populations was strikingly different in both the EBV+ subgroups (p<0.001) and the EBV- subgroups (p = 0.01). The mixed cellularity subtype was almost 3x more frequent amongst the Chinese (p<0.001).

Conclusion/significance: CHL patients from Northern regions of China show a distinctive age distribution pattern with a striking incidence peak of EBV+ mixed cellularity cases among children and adolescents and another high incidence peak of EBV- nodular sclerosis cases in young adults. In comparison to Dutch cHL patients there are pronounced differences in age distribution, subtype and EBV status, presumably caused by complex gene-environmental interactions.

Figure 1. Age distribution of Dutch and Chinese cHL patients in consecutive 10-year intervals.

Age distribution is shown for 157 patients from Northern regions of China (black) and 515 patients from the Northern part of the Netherlands (grey). The two curves exhibit a somewhat similar trend with significant differences at the first, second, eighth and ninth decade (* = p<0.01, ** = p<0.001) between the Chinese and the Dutch population (6% vs. 1%, 22% vs. 12%, 1% vs. 7% and 0% vs. 3% respectively). The Chinese population has more patients among the first three decades as compared to the Dutch population, both having the highest peak in the third decade. The Chinese population does not show a second incidence peak at around 60 years.

Figure 2. Age distribution of Dutch and Chinese cHL patients stratified by EBV status.

A represents the comparison of the age distribution in the two EBV+ cHL subpopulations. Chinese EBV+ cHL patients (black) exhibited a significant single peak in the first and second decade with a maximum percentage of 26% (* = p<0.01). In contrast, Dutch EBV+ cHL patients (grey) demonstrated a clear bimodal age distribution pattern with two peaks occurring in the third and seventh decade respectively with a similar incidence for both peaks (17% and 18%). B shows the age distribution curve of the EBV- cHL patients. There is a single incidence peak in the third decade for both populations, which is more pronounced in the Chinese population (39% vs. 27%).