Association between Epstein-Barr virus and periodontitis: A meta-analysis

Abstract

Purpose Previous studies have found that Epstein-Barr virus (EBV) is associated with periodontitis, though some controversy remains. This meta-analysis aimed to clarify and update the relationship between EBV and periodontitis as well as clinical parameters. Methods A comprehensive search was conducted in the PubMed and Scopus databases in December 2020. Original data were extracted according to defined inclusion and exclusion criteria. Outcomes were analyzed, including overall odds ratios (ORs) and 95% confidence intervals (CIs). A random-effects model was used, and publication bias was assessed by Egger’s and Begg’s tests. Sensitivity analysis was used to evaluate the stability of the outcome. Results Twenty-six studies were included in the present meta-analysis, involving 1354 periodontitis patients and 819 healthy controls. The included studies mostly showed high quality. The overall quantitative synthesis for the association between EBV and periodontitis was an increased odds ratio when subgingival EBV was detected OR = 7.069, 95% CI = 4.197–11.905, P<0.001). The results of subgroup analysis suggested that the association of EBV with periodontitis was significant in Asian, European, and American populations (P<0.001; P = 0.04; P = 0.003, respectively) but not in African populations (P = 0.29). Subgroup analysis by sample type showed that subgingival plaque (SgP), tissue and gingival crevicular fluid GCF were useful for EBV detection (P<0.001). EBV detection amplification methods included nested PCR, multiplex PCR and PCR (P<0.001; P = 0.05, P<0.001, respectively), but EBV detection by real-time PCR and loop-mediated isothermal amplification presented no significant result (P = 0.06; P = 0.3, respectively). For the clinical parameters of periodontitis, pocket depth (PD) and bleeding of probing (BOP) percentages were higher in the EBV-positive sites than in the EBV-negative sites (MD 0.47 [0.08, 0.85], P = 0.02; MD 19.45 [4.47, 34.43], P = 0.01). Conclusions A high frequency of EBV detection is associated with an increased risk of periodontitis. The EBV association was particularly significant in all populations except in African populations. Subgigival plaque (SgP), tissue and GCF were not significantly different useful material for detecting EBV in periodontitis. Nested PCR and multiplex PCR are reliable methods for this purpose. In the presence of EBV, PD and BOP are reliable clinical parameters for gingival inflammation. However, some caution in such interpretation is justified due to heterogeneity among studies. A suggested extension could assess the parallel influence of other human herpesviruses.

Evidence linking the association of periodontal viruses and pentraxins in periodontitis patients with coronary artery disease

“…In concurrence to our study, various clinical studies and meta‐analyses have reported EBV and CMV to have an association with periodontitis 26,31 . Various biological mechanisms of EBV have been proposed, such as its latent and lytic phases leading to a consistent periodontal infection, its coexistence with periodontopathogens like Porphyromonas gingivalis and Fusobacterium nucleatum , EBV‐encoded latent membrane protein 1, that induce pro‐inflammatory cytokines, thereby proving a significant association of EBV in the pathogenesis of periodontitis 6 . Adolfo Contreras et al.…”

“…26,31 Various biological mechanisms of EBV have been proposed, such as its latent and lytic phases leading to a consistent periodontal infection, its coexistence with periodontopathogens like Porphyromonas gingivalis and Fusobacterium nucleatum, EBV-encoded latent membrane protein 1, that induce pro-inflammatory cytokines, thereby proving a significant association of EBV in the pathogenesis of periodontitis. 6 Adolfo Contreras et al have also suggested CMV as a major suspected periodontal pathogen along with the gram-negative periodontal microbiome. Furthermore, CMV-infected gingival cells showed a suppressed collagen and increased matrix metalloproteinase production, which in turn exacerbates the progression of periodontitis.…”

“…5 EBV is a gamma herpes virus found in higher percentage in deeper periodontal pockets and saliva of periodontitis patients. 6 CMV belongs to the beta-herpes virus family, which has been reported to contribute to the episodic nature of periodontal disease and is also more prevalent in periodontal pockets. 7 Finally, there is limited evidence of a positive association between HSV and periodontal disease site, and in contrast, little evidence has been found suggesting no difference in HSV prevalence between healthy and periodontal pockets.…”

“…EBV is a gamma herpes virus found in higher percentage in deeper periodontal pockets and saliva of periodontitis patients 6 . CMV belongs to the beta‐herpes virus family, which has been reported to contribute to the episodic nature of periodontal disease and is also more prevalent in periodontal pockets 7 .…”

Calculus as a Risk Factor for Periodontal Disease: Narrative Review on Treatment Indications When the Response to Scaling and Root Planing Is Inadequate

“…There is general agreement that plaque/biofilm consisting of a community of bacteria and other microbiota, e.g., viruses and protozoa, is the initial cause of periodontal disease [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Because of the extensive literature supporting plaque as the “cause” of periodontal disease, there has been a relative deemphasis on the role of calculus in the persistence and progression of periodontal disease.…”