Rassekh C H, Rady P L, Arany I, Tyring S K, Knudsen S, Calhoun K H, Seikaly H, Bailey B J
Department of Otolaryngology, University of Texas Medical Branch, Galveston 77555-0521, USA.
Laryngoscope. 1998 Mar;108(3):362-7. doi: 10.1097/00005537-199803000-00010.
Epstein-Barr virus (EBV) has been shown to be a likely etiologic agent in nasopharyngeal carcinogenesis. Human papillomaviruses (HPVs) have previously been identified in numerous upper aerodigestive tract carcinomas. This pilot study was undertaken to investigate the prevalence of combined EBV and HPV infection in 17 patients with nasopharyngeal carcinoma (NPCA) using polymerase chain reaction (PCR). The primary goal was to determine if the presence of HPV could be correlated with molecular, histologic, or clinical parameters. There were seven patients with undifferentiated NPCA (World Health Organization [WHO] type III) and 10 patients with squamous cell carcinoma (WHO type I). All 17 patients had stage IV disease at presentation. EBV was identified in 15 patients (88.2%), and HPV subtypes were identified in samples from nine patients (52.9%). All HPV-positive cases were also EBV positive. Western blot analysis of six samples showed a high level of expression of c-myc and cdc2 kinase and a low level of p53 protein in NPCAs that contained both HPV and EBV (n = 3). Increased expression of c-myc and cdc2 kinase was seen in the cases that contained EBV only, but to a lesser extent (n = 2). These findings indicate an effect of the virus on cellular proliferation and differentiation. Similarly, an elevated level of Rb protein was found only in the HPV-containing NPCAs. Moderate differentiation (keratinization) occurred in four of eight HPV-negative and none of the nine HPV-positive NPCAs. (All HPV-positive cases were poorly differentiated or undifferentiated.) This difference is statistically significant for this sample size (P < 0.03). There was a trend for the group that was HPV positive to have WHO III histology and for the HPV-negative group to have WHO I. The presence of HPV could not be correlated with any clinical parameters in this small group of patients with advanced disease; however, these data suggest that coexistence of EBV and HPV infection may be a factor in the pathogenesis of NPCA and may have an effect on regulation of cellular proliferation and differentiation.
爱泼斯坦-巴尔病毒（EBV）已被证明可能是鼻咽癌发生的病因。此前在众多上呼吸道消化道癌中已鉴定出人乳头瘤病毒（HPV）。本初步研究采用聚合酶链反应（PCR）来调查17例鼻咽癌患者（NPCA）中EBV和HPV合并感染的患病率。主要目的是确定HPV的存在是否与分子、组织学或临床参数相关。有7例未分化NPCA患者（世界卫生组织[WHO]III型）和10例鳞状细胞癌患者（WHO I型）。所有17例患者初诊时均为IV期疾病。15例患者（88.2%）检测到EBV，9例患者（52.9%）的样本中鉴定出HPV亚型。所有HPV阳性病例也均为EBV阳性。对6个样本进行的蛋白质印迹分析显示，在同时含有HPV和EBV的NPCA中（n = 3），c-myc和cdc2激酶表达水平高，p53蛋白水平低。仅含有EBV的病例中可见c-myc和cdc2激酶表达增加，但程度较轻（n = 2）。这些发现表明病毒对细胞增殖和分化有影响。同样，仅在含有HPV的NPCA中发现Rb蛋白水平升高。8例HPV阴性的NPCA中有4例发生中度分化（角化），9例HPV阳性的NPCA中无一例发生中度分化。（所有HPV阳性病例均为低分化或未分化。）对于该样本量，这种差异具有统计学意义（P < 0.03）。HPV阳性组有WHO III组织学类型的趋势，HPV阴性组有WHO I组织学类型的趋势。在这一小群晚期疾病患者中，HPV的存在与任何临床参数均无相关性；然而，这些数据表明EBV和HPV感染共存可能是NPCA发病机制中的一个因素，并且可能对细胞增殖和分化的调节有影响。
