BackgroundHuman herpesvirus-6 (HHV-6) is a ubiquitous double-stranded DNA virus that can cause roseola infantum, encephalitis, and seizure disorders. Several studies have shown an association between HHV-6 and cancer but confirmation of an etiologic role is lacking. We reviewed the criteria for viral causation of cancer used by The International Agency for Research on Cancer (IARC) for six oncogenic viruses and applied criteria to published reports of HHV-6 and its association with Hodgkin lymphoma and brain tumors.MethodsOur major criteria for oncogenicity were finding evidence of the virus in every tumor cell and prevention of the tumor by an antiviral vaccine. Our six minor criteria included: 1) suggestive serologic correlation, such as higher virus antibody levels in cases compared to controls; 2) evidence of the virus in some but not all tumor cells, and 3) time space clustering. We focused on Epstein-Barr virus (EBV) as the primary virus for comparison as HHV-6 and EBV are both Herpesviridae, ubiquitous infections, and EBV is well-accepted as a human oncovirus. Particular attention was given to Hodgkin lymphoma (HL) and brain cancer as these malignancies have been the most studied.ResultsNo studies reported HHV-6 satisfying either of the major criteria for oncogenicity. Of the minor criteria used by IARC, serologic studies have been paramount in supporting EBV as an oncogenic agent in all EBV-associated tumors, but not for HHV-6 in HL or brain cancer. Clustering of cases was suggestive for both HL and brain cancer and medical intervention suggested by longer survival in patients treated with antiviral agents was reported for brain cancer.ConclusionThere is insufficient evidence to indicate HHV-6 is an etiologic agent with respect to HL and brain cancers. We suggest that methods demonstrating EBV oncogenicity be applied to HHV-6. It is important that one study has found HHV-6 in all cancer cells in oral cancer in a region with elevated HHV-6 antibodies and therefore HHV-6 can still be considered a possible human oncogenic virus.

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使用 IARC 致癌性标准评估 HHV-6 作为霍奇金淋巴瘤和脑癌的病因


背景人类疱疹病毒 6 (HHV-6) 是一种普遍存在的双链 DNA 病毒，可引起婴儿玫瑰疹、脑炎和癫痫发作。多项研究表明 HHV-6 与癌症之间存在关联，但缺乏对其病因作用的确认。我们回顾了国际癌症研究机构 (IARC) 对六种致癌病毒使用的病毒致癌标准，并将该标准应用于已发表的 HHV-6 及其与霍奇金淋巴瘤和脑肿瘤的关联报告。方法我们的致癌性主要标准我们正在每个肿瘤细胞中寻找病毒的证据，并通过抗病毒疫苗预防肿瘤。我们的六个次要标准包括：1）提示性血清学相关性，例如与对照相比，病例中病毒抗体水平较高； 2) 一些但不是所有肿瘤细胞中存在病毒的证据，以及 3) 时空聚类。我们重点关注 Epstein-Barr 病毒 (EBV) 作为主要病毒进行比较，因为 HHV-6 和 EBV 都是疱疹病毒科，普遍存在感染，并且 EBV 被广泛认为是人类肿瘤病毒。特别关注霍奇金淋巴瘤 (HL) 和脑癌，因为这些恶性肿瘤的研究最多。结果没有研究报告 HHV-6 满足任一主要致癌性标准。在 IARC 使用的次要标准中，血清学研究对于支持 EBV 作为所有 EBV 相关肿瘤的致癌剂至关重要，但对于 HL 或脑癌中的 HHV-6 则不然。病例聚集提示 HL 和脑癌，并且据报道，接受抗病毒药物治疗的患者生存期更长，表明医疗干预对脑癌有帮助。 结论 没有足够的证据表明 HHV-6 是 HL 和脑癌的病因。 我们建议将证明 EBV 致癌性的方法应用于 HHV-6。重要的是，一项研究发现口腔癌的所有癌细胞中 HHV-6 抗体升高的区域中存在 HHV-6，因此 HHV-6 仍然可以被认为是一种可能的人类致癌病毒。