Hjalgrim Henrik, Askling Johan, Rostgaard Klaus, Hamilton-Dutoit Stephen, Frisch Morten, Zhang Jin-Song, Madsen Mette, Rosdahl Nils, Konradsen Helle Bossen, Storm Hans H, Melbye Mads
Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Institut, Copenhagen, Denmark.
N Engl J Med. 2003 Oct 2;349(14):1324-32. doi: 10.1056/NEJMoa023141.
Infectious mononucleosis-related Epstein-Barr virus (EBV) infection has been associated with an increased risk of Hodgkin's lymphoma in young adults. Whether the association is causal remains unclear.
We compared the incidence rates of Hodgkin's lymphoma in two population-based Danish cohorts of patients who were tested for infectious mononucleosis: 17,045 with serologic evidence of having had acute EBV infection, and 24,614 with no such evidence. We combined the cohort of patients who had serologically verified infectious mononucleosis with a cohort of 21,510 Swedish patients with infectious mononucleosis (combined total, 38,555). Biopsy specimens of Hodgkin's lymphomas occurring during follow-up in this combined cohort were tested serologically for the presence of EBV. Using this information, we modeled the relative risk of EBV-negative and EBV-positive Hodgkin's lymphoma in different periods after the diagnosis of infectious mononucleosis and estimated the median incubation time for mononucleosis-related EBV-positive Hodgkin's lymphoma.
Only serologically confirmed infectious mononucleosis was associated with a persistently increased risk of Hodgkin's lymphoma. Sixteen of 29 tumors (55 percent), obtained from patients with infectious mononucleosis, had evidence of EBV. There was no evidence of an increased risk of EBV-negative Hodgkin's lymphoma after infectious mononucleosis. In contrast, the risk of EBV-positive Hodgkin's lymphoma was significantly increased (relative risk, 4.0; 95 percent confidence interval, 3.4 to 4.5). The estimated median incubation time from mononucleosis to EBV-positive Hodgkin's lymphoma was 4.1 years (95 percent confidence interval, 1.8 to 8.3).
A causal association between infectious mononucleosis-related EBV infection and the EBV-positive subgroup of Hodgkin's lymphomas is likely in young adults.
传染性单核细胞增多症相关的爱泼斯坦-巴尔病毒（EBV）感染与年轻成年人患霍奇金淋巴瘤的风险增加有关。这种关联是否为因果关系仍不清楚。
我们比较了丹麦两个基于人群的队列中霍奇金淋巴瘤的发病率，这两个队列中的患者均接受了传染性单核细胞增多症检测：17045例有急性EBV感染血清学证据的患者，以及24614例无此类证据的患者。我们将血清学证实患有传染性单核细胞增多症的患者队列与21510例瑞典传染性单核细胞增多症患者队列合并（合并总数为38555例）。对该合并队列随访期间发生的霍奇金淋巴瘤活检标本进行EBV血清学检测。利用这些信息，我们模拟了传染性单核细胞增多症诊断后不同时期EBV阴性和EBV阳性霍奇金淋巴瘤的相对风险，并估计了与单核细胞增多症相关的EBV阳性霍奇金淋巴瘤的中位潜伏期。
只有血清学证实的传染性单核细胞增多症与霍奇金淋巴瘤风险持续增加有关。从传染性单核细胞增多症患者中获取的29个肿瘤中有16个（55%）有EBV证据。没有证据表明传染性单核细胞增多症后EBV阴性霍奇金淋巴瘤风险增加。相比之下，EBV阳性霍奇金淋巴瘤的风险显著增加（相对风险，4.0；95%置信区间，3.4至4.5）。从单核细胞增多症到EBV阳性霍奇金淋巴瘤的估计中位潜伏期为4.1年（95%置信区间，1.8至8.3）。
在年轻成年人中，传染性单核细胞增多症相关的EBV感染与霍奇金淋巴瘤的EBV阳性亚组之间可能存在因果关联。
