Laboratoire de Virologie Moléculaire, UMR5537, C,N,R,S, Faculté de Médecine R,T,H, Laennec, Lyon, France.
Virol J. 2013 Nov 19;10:340. doi: 10.1186/1743-422X-10-340.
Despite the fact that the implication of human papillomavirus (HPV) in the carcinogenesis and prognosis of cervical cancer is well established, the impact of a co-infection with high risk HPV (HR-HPV) and Epstein-Barr virus (EBV) is still not fully understood.
Fifty eight randomly selected cases of squamous cell carcinomas (SCC) of the uterine cervix, 14 normal cervices specimens, 21 CIN-2/3 and 16 CIN-1 cases were examined for EBV and HPV infections. Detection of HR-HPV specific sequences was carried out by PCR amplification using consensus primers of Manos and by Digene Hybrid Capture. The presence of EBV was revealed by amplifying a 660 bp specific EBV sequence of BALF1. mRNA expression of LMP-1 in one hand and protein levels of BARF-1, LMP-1 and EBNA-1 in the other hand were assessed by RT-PCR and immunoblotting and/or immunohischemistry respectively.
HR-HPV infection was found in patients with SCC (88%), low-grade (75%) and high grade (95%) lesions compared to only 14% of normal cervix cases. However, 69%, 12.5%, 38.1%, and 14% of SCC, CIN-1, CIN-2/3 and normal cervix tissues, respectively, were EBV infected. The highest co-infection (HR-HPV and EBV) was found in squamous cell carcinoma cases (67%). The latter cases showed 27% and 29% expression of EBV BARF-1 and LMP-1 oncogenes respectively.
The high rate of HR-HPV and EBV co-infection in SCC suggests that EBV infection is incriminated in cervical cancer progression. This could be taken into account as bad prognosis in this type of cancer. However, the mode of action in dual infection in cervical oncogenesis needs further investigation.
尽管人乳头瘤病毒(HPV)在宫颈癌的发生和预后中的作用已得到充分证实,但高危型 HPV(HR-HPV)和 Epstein-Barr 病毒(EBV)合并感染的影响仍不完全清楚。
随机选择 58 例宫颈鳞状细胞癌(SCC)、14 例正常宫颈标本、21 例 CIN-2/3 和 16 例 CIN-1 病例,检测 EBV 和 HPV 感染。采用 Manos 共识引物的 PCR 扩增检测 HR-HPV 特异序列,采用 Digene Hybrid Capture 检测。通过扩增 BALF1 的 660 bp 特异性 EBV 序列检测 EBV 的存在。采用 RT-PCR 和免疫印迹和/或免疫组化分别评估 LMP-1 的 mRNA 表达和 BARF-1、LMP-1 和 EBNA-1 的蛋白水平。
HR-HPV 感染见于 SCC(88%)、低级别病变(75%)和高级别病变(95%)患者,而正常宫颈病例仅为 14%。然而,69%、12.5%、38.1%和 14%的 SCC、CIN-1、CIN-2/3 和正常宫颈组织分别感染 EBV。HPV 和 EBV 合并感染率最高见于 SCC 病例(67%)。这些病例 EBV BARF-1 和 LMP-1 癌基因的表达率分别为 27%和 29%。
SCC 中 HR-HPV 和 EBV 合并感染率高提示 EBV 感染与宫颈癌进展有关。这可能被视为此类癌症的不良预后因素。然而,在宫颈癌发生中双重感染的作用模式仍需进一步研究。