Si Hua Xin, Tsao Sai Wah, Poon Cycles Suet Ping, Wong Yong Chuan, Cheung Annie Lai Man
Department of Anatomy, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong SAR, PR China.
J Clin Virol. 2005 Jan;32(1):19-23. doi: 10.1016/j.jcv.2004.04.004.
Infection with high-risk human papillomavirus (HPV) has been implicated as one of the risk factors of esophageal squamous cell carcinoma (ESCC). Integration of viral DNA into host genome is essential for carcinogenesis since it promotes disruption of the HPV E2 gene, leading to abnormal expression of E6 and E7 oncoproteins.
To investigate the viral integration status of HPV-16 infection in ESCC, 35 HPV-positive ESCC specimens collected from Chinese patients were subject to real-time quantitative PCR for determination of physical status of HPV-16 by analyzing the ratios of E2 to E6 genes.
Our results showed that only 8.6% (3/35) of the HPV-16 positive specimens harbored exclusively the episomal form (i.e. E2/E6 ratio > or = 1), whereas the remaining 91.4% contained either only the integrated form (5.7%, with E2/E6 ratio = 0) or a mixture of episomal and integrated forms of viral molecules (85.7%, with E2/E6 ratios > 0 but < 1). Amongst the 30 cancer specimens carrying mixed integrated and episomal forms, 28 had E2/integrated E6 ratios of less than 1, indicating a predominance of integrated form of viral genes in these lesions.
Our finding of frequent integration of viral DNA in the host genome suggests that integration HPV-16 is common in ESCC from Chinese patients and implies that HPV infection may play a role in the pathogenesis of ESCC.
高危型人乳头瘤病毒(HPV)感染被认为是食管鳞状细胞癌(ESCC)的危险因素之一。病毒DNA整合到宿主基因组中对于致癌作用至关重要,因为它会导致HPV E2基因破坏,进而导致E6和E7癌蛋白异常表达。
为了研究ESCC中HPV-16感染的病毒整合状态,对35例来自中国患者的HPV阳性ESCC标本进行实时定量PCR,通过分析E2与E6基因的比例来确定HPV-16的物理状态。
我们的结果显示,HPV-16阳性标本中仅有8.6%(3/35)仅含有游离型(即E2/E6比例≥1),而其余91.4%要么仅含有整合型(5.7%,E2/E6比例=0),要么含有病毒分子游离型和整合型的混合形式(85.7%,E2/E6比例>0但<1)。在30例携带整合型和游离型混合形式的癌标本中,28例的E2/整合型E6比例小于1,表明这些病变中病毒基因以整合型为主。
我们发现病毒DNA在宿主基因组中频繁整合,这表明HPV-16整合在中国患者的ESCC中很常见,意味着HPV感染可能在ESCC的发病机制中起作用。