Mutirangura A
Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Ann N Y Acad Sci. 2001 Sep;945:59-67.
Following reports describing circulating tumor DNA, serum/plasma viral nucleic acid has shown its potential as a new diagnostic target in cancer. In the majority of examples of viral carcinogenesis, the viral genome is consistently present in certain tumors and serves as an effective marker. This article reviews recent findings, proposes possible mechanisms, and examines the potential clinical application of serum/plasma Epstein-Barr virus (EBV) DNA in nasopharyngeal cancer (NPC) and human papillomavirus (HPV) DNA in cervical carcinoma (CC). These tumors share a DNA viral etiology and present similar histopathological findings. However, plasma EBV and HPV DNA are distinct in several aspects, including incidence, mechanism of release from tumor, and clinical application. Both circulating cell-free EBV and HPV DNA reveal the same viral type as their matched tumors, indicating both are derived from the neoplastic tissue. Plasma viral DNA incidence and copy number are high in NPC, but low in HPV-associated cancers. Whereas much EBV DNA in NPC is episomal, the resistance to DNase treatment of serum EBV DNA and evidence confirming lytic EBV replication in NPC suggest that a reasonable proportion of plasma EBV DNA is virions. On the contrary, plasma HPV genomes, as in CC, integrate into host chromosome. Plasma EBV DNA copy number, by quantitative PCR, is related to tumor mass, predicts prognosis, measures immediate response to treatment, and is useful in early detection of recurrence. Plasma HPV DNA, on the other hand, is associated with and can be considered as an early tumor marker for distant metastasis.
在有关循环肿瘤DNA的报道之后，血清/血浆病毒核酸已显示出其作为癌症新诊断靶点的潜力。在大多数病毒致癌的例子中，病毒基因组始终存在于某些肿瘤中，并作为一种有效的标志物。本文综述了近期的研究发现，提出了可能的机制，并探讨了血清/血浆中爱泼斯坦-巴尔病毒（EBV）DNA在鼻咽癌（NPC）以及人乳头瘤病毒（HPV）DNA在宫颈癌（CC）中的潜在临床应用。这些肿瘤具有相同的DNA病毒病因，且呈现相似的组织病理学表现。然而，血浆EBV和HPV DNA在几个方面存在差异，包括发生率、从肿瘤中释放的机制以及临床应用。循环游离的EBV和HPV DNA均与其匹配的肿瘤显示相同的病毒类型，表明两者均来源于肿瘤组织。血浆病毒DNA在NPC中的发生率和拷贝数较高，但在HPV相关癌症中较低。虽然NPC中的许多EBV DNA是游离型的，但血清EBV DNA对DNA酶处理的抗性以及证实NPC中EBV进行裂解复制的证据表明，血浆EBV DNA中有相当一部分是病毒颗粒。相反，血浆HPV基因组，如在CC中一样，整合到宿主染色体中。通过定量PCR检测，血浆EBV DNA拷贝数与肿瘤大小相关，可预测预后，衡量对治疗的即时反应，并有助于早期检测复发。另一方面，血浆HPV DNA与远处转移相关，可被视为远处转移的早期肿瘤标志物。
