爱泼斯坦-巴尔病毒（EBV）作为人乳头瘤病毒（HPV）相关宫颈癌发生的辅助因子的潜在作用。

Possible contributing role of Epstein-Barr virus (EBV) as a cofactor in human papillomavirus (HPV)-associated cervical carcinogenesis.

作者信息

Aromseree Sirinart, Pientong Chamsai, Swangphon Piyawut, Chaiwongkot Arkom, Patarapadungkit Natcha, Kleebkaow Pilaiwan, Tungsiriwattana Thumwadee, Kongyingyoes Bunkerd, Vendrig Tineke, Middeldorp Jaap M, Ekalaksananan Tipaya

机构信息

Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; HPV & EBV and carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.

Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

出版信息

J Clin Virol. 2015 Dec;73:70-76. doi: 10.1016/j.jcv.2015.10.015. Epub 2015 Oct 23.

DOI:10.1016/j.jcv.2015.10.015

PMID:26551071

Abstract

BACKGROUND

Persistent infection with EBV has been linked to the development of malignancies including HPV-associated cervical carcinoma. However, the role of EBV in HPV-associated cervical cancer is still poorly understood.

OBJECTIVE

To determine the possible contributing role of EBV in HPV-associated cervical carcinogenesis according to HPV genotypes, HPV genome status and EBV localization.

STUDY DESIGN

Cervical tissues, including 82 with no squamous intraepithelial lesions (noSILs), 85 low-grade SILs (LSILs), 85 high grade SILs (HSILs) and 40 squamous cell carcinoma samples (SCC) were investigated using PCR and dot blot hybridization for EBV detection and PCR and reverse line blot hybridization for HPV genotyping. The amplification of papillomavirus oncogene transcripts assay and in situ hybridization were used to determine HPV physical status and EBV EBER localization, respectively.

RESULTS

EBV was detected increasingly from noSIL (13.4%), LSIL (29.4%) to HSIL (49.4%) samples. The prevalence of HPV-EBV co-infection was significantly higher in any grade of lesion than in noSIL samples (p<0.05) including noSIL (1.2%; 95% confidence intervals [CI]=0.0-3.6%, relative risk [RR]=1), LSIL (18.8%, 95% CI=10.5-27.1%, RR=15.4), HSIL (41.2%, 95% CI=30.7-51.6%, RR=33.8) and SCC (30.0%, 95% CI=15.8-44.2%, RR=24.6). Interestingly, HPV-EBV co-infection was more common in cases with episomal forms of high-risk (HR) HPV whereas HPV alone was more common in cases with integrated HR-HPV. In addition, EBER staining demonstrated that EBV was mainly present in infiltrating lymphocytes.

CONCLUSION

Infiltrating EBV-infected lymphocytes may play a role in cancer progression of cervical lesion containing episomal HR-HPV.

摘要

背景

EBV的持续感染与包括HPV相关宫颈癌在内的多种恶性肿瘤的发生有关。然而，EBV在HPV相关宫颈癌中的作用仍知之甚少。

目的

根据HPV基因型、HPV基因组状态和EBV定位，确定EBV在HPV相关宫颈癌发生中的可能作用。

研究设计

使用PCR和斑点杂交检测EBV，PCR和反向线印迹杂交进行HPV基因分型，对82例无鳞状上皮内病变（noSIL）、85例低级别鳞状上皮内病变（LSIL）、85例高级别鳞状上皮内病变（HSIL）和40例鳞状细胞癌样本（SCC）的宫颈组织进行研究。分别采用乳头瘤病毒癌基因转录本扩增检测法和原位杂交法确定HPV的物理状态和EBV EBER的定位。

结果

从无SIL（13.4%）、LSIL（29.4%）到HSIL（49.4%）样本中，EBV的检出率逐渐升高。在任何级别的病变中，HPV-EBV合并感染的患病率均显著高于无SIL样本（p<0.05），包括无SIL（1.2%；95%置信区间[CI]=0.0-3.6%，相对风险[RR]=1）、LSIL（18.8%，95%CI=10.5-27.1%，RR=15.4）、HSIL（41.2%，95%CI=30.7-51.6%，RR=33.8）和SCC（30.0%，95%CI=15.8-44.2%，RR=24.6）。有趣的是，HPV-EBV合并感染在高危（HR）HPV游离型病例中更为常见，而单纯HPV感染在HR-HPV整合型病例中更为常见。此外，EBER染色显示EBV主要存在于浸润淋巴细胞中。