Epstein-Barr virus infection and oral squamous cell carcinoma risk: A meta-analysis

PLOS ONE, Nov 2019

Background The evidence for association between Epstein-Barr virus (EBV) infection and risk of oral squamous cell carcinoma (OSCC) is inconsistent in the literature. Therefore, this meta-analysis was conducted to clarify this association. Methods A literature search was conducted in electronic databases for English- and Chinese-language publications until March 31, 2017 to include eligible case-control studies. The pooled odds ratio (OR) and 95% confidence interval (95% CI) were estimated to determine the association between EBV infection and OSCC risk using a fixed- or random-effects model based on heterogeneity. Publication bias was assessed using funnel plot analysis. Results A total of 13 case-control studies with 686 OSCC patients and 433 controls were included based on predetermined inclusion and exclusion criteria. The pooled OR with 95% CI between EBV infection and OSCC risk was 5.03 (1.80–14.01) with significant heterogeneity observed (I2 = 87%). The subgroup analysis indicates that the year of publication, study location, economic level, sample size, tissue type, detection method and marker, control type, and language might explain potential sources of heterogeneity. Publication bias was not observed, and sensitivity analysis showed stable results. Conclusions The results of the current meta-analysis suggest that EBV infection is statistically associated with increased risk of OSCC. However, additional high-quality studies with larger sample sizes are needed to further confirm the relationship between EBV and OSCC.

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Epstein-Barr virus infection and oral squamous cell carcinoma risk: A meta-analysis

October Epstein-Barr virus infection and oral squamous cell carcinoma risk: A meta- analysis Yangyang She 0 1 Xiaolin Nong 0 1 Min Zhang 0 Menglin Wang 0 0 Editor: Edward Gershburg, Southern Illinois University School of Medicine , UNITED STATES 1 Department of Oral and Maxillofacial Surgery, College and Hospital of Stomatology, Guangxi Medical University , Nanning, Guangxi , China , 2 Department of Prosthodontics, College and Hospital of Stomatology, Peking University , Beijing , China , 3 Department of Otorhinolaryngology and Head and Neck Surgery, The First Affiliated Hospital of Guangxi Medical University , Nanning, Guangxi , China Conclusions The results of the current meta-analysis suggest that EBV infection is statistically associated with increased risk of OSCC. However, additional high-quality studies with larger sample sizes are needed to further confirm the relationship between EBV and OSCC. The evidence for association between Epstein-Barr virus (EBV) infection and risk of oral squamous cell carcinoma (OSCC) is inconsistent in the literature. Therefore, this meta-analysis was conducted to clarify this association. A literature search was conducted in electronic databases for English- and Chinese-language publications until March 31, 2017 to include eligible case-control studies. The pooled odds ratio (OR) and 95% confidence interval (95% CI) were estimated to determine the association between EBV infection and OSCC risk using a fixed- or random-effects model based on heterogeneity. Publication bias was assessed using funnel plot analysis. a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This study was funded by National Natural Science Foundation of China (81360404, http://www.nsfc.gov.cn/); Guangxi Natural Science Foundation (0832013, http://gxnsf.gxsti.net/stms/ login.jsp); Innovation Project of Guangxi Graduate Education (201010598RY10), funding receiver XLN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Background Methods Results Introduction Oral squamous cell carcinoma (OSCC) is the most common subset (90%) of oral cancer with a global incidence of 275,000 cases annually [ 1 ], the sixth leading malignancy worldwide [ 2 ]. It results from the outgrowth of the mucosal epithelium. Local recurrence and regional and distant metastases can occur even decades after surgery, radiation, and chemotherapy, making OSCC life-threatening [3]. The 5-year survival rate of late-stage OSCC is only 20% [1]. The high disease burden and low survival rate highlight the need to better understand the etiology of OSCC. Established risk factors for OSCC involve long-term betel quid chewing, tobacco smoking, and alcohol drinking [4±6]. In addition, numerous other possible risk factors have also been proposed. Recently, it has been demonstrated that individuals with Epstein-Barr virus (EBV) infection might be at increased risk for OSCC. EBV is an oncogenic human herpes virus that contains double-stranded DNA, known as the first human tumor virus [ 7,8 ]. It appears even in asymptomatic individuals, persisting for lifelong latent infection [7]. EBV has been well proposed as a causative agent for several types of epithelial cell malignancies, such as nasopharyngeal carcinoma (NPC) [ 9 ]. Furthermore, evidence has shown that EBV is involved in B-lymphocytic cell malignancies, such as Burkitt's lymphoma and Hodgkin lymphoma [ 7,10 ]. The strength and consistency of EBV DNA present in OSCC indicate a potentially impor tant role of EBV infection on OSCC pathogenesis. However, controversial results have been reported [11±13]. Therefore, a meta-analysis was conducted to assess the association between EBV infection and OSCC risk. Methods and materials Search strategy The current meta-analysis was conducted based on the Meta-Analysis of Observational Studies in Epidemiology guidelines [ 14 ]. Pubmed, Web of Science, Cochrane, and Embase databases for English-language publications and China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Scientific Journals Fulltext Database (CQVIP), and China Biology Medicine disc (CBM disc) for Chinese-language publications were searched until March 31, 2017. Keywords used for the Pubmed search are as follows: Search ((((ªEpstein-Barr Virusº[Title/Abstract]) or ªEBVº[Title/Abstract]) or ªhuman herpesvirus 4º[Title/Abstract]) or ªHHV 4º[Title/Abstract]) and ((((((((ªoral squamous cell carcinomaº[Title/Abstract]) or ªOSCCº[Ti tle/Abstract]) or ªoral carcinomaº[Title/Abstract]) or ªoral cancerº[Title/Abstract]) or ªtongue cancerº[Title/Abstract]) or ªbuccal cancerº[Title/Abstract]) or ªoral lesionsº[Title/Abstract]) or (ªhead and neck cancerº[Title/Abstract])). Similar search was conducted in the Web of Science, Cochrane, (...truncated)


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Yangyang She, Xiaolin Nong, Min Zhang, Menglin Wang. Epstein-Barr virus infection and oral squamous cell carcinoma risk: A meta-analysis, PLOS ONE, 2017, Volume 12, Issue 10, DOI: 10.1371/journal.pone.0186860