de Lima Marcos Antonio Pereira, Teodoro Ilara Parente Pinheiro, Galiza Lara Eduardo de, Filho Pedro Hugo Bezerra Maia, Marques Fernanda de Morais, Pinheiro Junior Roberto Flávio Fontenelle, Macedo Geamberg Einstein Cruz, Facundo Heberty Tarso, da Silva Cláudio Gleidiston Lima, Lima Marcos Venício Alves
School of Medicine, Federal University of Cariri, UFCA, Barbalha, Ceará, Brazil.
Ceará Cancer Institute, ICC, Fortaleza, Ceará, Brazil.
Crit Rev Oncog. 2019;24(4):349-368. doi: 10.1615/CritRevOncog.2019031897.
The purpose of this meta-analysis is to evaluate the association of Epstein-Barr virus (EBV) with oral squamous cell carcinoma (OSCC). We searched the electronic scientific databases of PubMed and Scopus and included a total of 53 studies that were published from 1990 to 2019. The analysis yielded a 45.37% (95% confidence interval [CI]: 38.90-51.84; p < 0.001) overall pooled prevalence of EBV. Studies that used the applied methods of in situ hybridization, polymerase chain reaction, immunology, or RNA microarray showed the following pooled prevalence: 46.08%, 40.32, 54.97%, and 74.89%, respectively. EBV-infected individuals have a 2.5 higher risk for developing OSCC (odds ratio: 2.57; 95% CI: 1.23% to 5.36%; p < 0.001). The present meta-analysis supports the hypothesis of EBV association with OSCC, pointing to this virus as a risk factor for neoplasia. Our findings also suggest that EBV latent transcripts (latent membrane protein 1, EBV nuclear antigen 1 and 2, and EBV-encoded small RNAs) have an important role in this process. Furthermore, novel advancements could arise from large and standardized studies that are constructed to probe for other latent gene expression, eliminate confounding factors (tobacco, alcohol, and high-risk human papillomavirus infection), and define the relationship between EBV and oral carcinomas.
本荟萃分析的目的是评估爱泼斯坦-巴尔病毒（EBV）与口腔鳞状细胞癌（OSCC）之间的关联。我们检索了PubMed和Scopus电子科学数据库，共纳入了1990年至2019年发表的53项研究。分析得出EBV的总体合并患病率为45.37%（95%置信区间[CI]：38.90 - 51.84；p < 0.001）。使用原位杂交、聚合酶链反应、免疫学或RNA微阵列等应用方法的研究显示的合并患病率分别为：46.08%、40.32%、54.97%和74.89%。EBV感染个体发生OSCC的风险高出2.5倍（优势比：2.57；95% CI：1.23%至5.36%；p < 0.001）。本荟萃分析支持EBV与OSCC相关的假说，指出该病毒是肿瘤形成的一个风险因素。我们的研究结果还表明，EBV潜伏转录本（潜伏膜蛋白1、EBV核抗原1和2以及EBV编码的小RNA）在这一过程中发挥重要作用。此外，针对其他潜伏基因表达进行探究、消除混杂因素（烟草、酒精和高危人乳头瘤病毒感染）并明确EBV与口腔癌之间关系的大型标准化研究可能会带来新的进展。
