Association Of Epstein-Barr Virus Research Articles

Early change of plasma Epstein-Barr virus DNA load and the viral lytic genome level could positively predict clinical outcome in recurrent or metastatic nasopharyngeal carcinoma receiving anti-programmed cell death 1 monotherapy

PurposePatients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials.MethodsPatients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined “EBV response” as 3 consecutive timepoints of load below 50% of baseline, and “EBV progression” as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples.ResultsWe found that the baseline EBV DNA load was positively correlated with tumor size (spearman p < 0.001). Both partial response (PR) and stable disease (SD) patients had significantly lower EBV load than progression disease (PD) patients. EBV assessment was highly consistent with radiographic evaluation. Patients with EBV response had significantly improved overall survival (OS) than patients with EBV progression (log-rank p = 0.004, HR = 0.351 [95% CI: 0.171–0.720], median 22.5 vs. 11.9 months). The median time to initial EBV response and progression were 25 and 36 days prior to initial radiographic response and progression, respectively. Patients with high levels of EBV lytic genomes at baseline, including BKRF2, BKRF3 and BKRF4, had better progression-free survival (PFS) and OS.ConclusionIn summary, early clearance of plasma EBV DNA load and high levels of lytic EBV genes were associated with better clinical outcome in patients with RM-NPC receiving anti-PD-1 monotherapy.

Association of Human Papilloma Virus, Cytomegalovirus, and Epstein-Barr Virus with Breast Cancer in Jordanian Women.

Background and Objectives: The investigation of oncogenic viruses and their potential association with breast cancer (BC) remains an intriguing area of study. The current work aims to assess evidence of three specific viruses, human papillomavirus (HPV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in BC samples and to explore their relationship with relevant clinicopathological variables. Materials and Methods: The analysis involved BC samples from 110 Jordanian female patients diagnosed with BC and breast tissue samples from 30 control patients with no evidence of breast malignancy, investigated using real-time PCR. The findings were then correlated with various clinico-pathological characteristics of BC. Results: HPV was detected in 27 (24.5%), CMV in 15 (13.6%), and EBV in 18 (16.4%) BC patients. None of the control samples was positive for HPV or CMV while EBV was detected in only one (3.3%) sample. While (HPV/EBV), (HPV/CMV), and (EBV/CMV) co-infections were reported in 1.8%, 2.7%, and 5.5%, respectively, coinfection with the three viruses (HPV/CMV/EBV) was not reported in our cohort. A statistically significant association was observed between HPV status and age (p = 0.047), and between clinical stage and CMV infection (p = 0.015). Conclusions: Our findings indicate the presence or co-presence of HPV, CMV, and EBV in the BC subpopulation, suggesting a potential role in its development and/or progression. Further investigation is required to elucidate the underlying mechanisms that account for the exact role of oncoviruses in breast carcinogenesis.

Deciphering the Association of Epstein-Barr Virus and Its Glycoprotein M Peptide with Neuropathologies in Mice.

The reactivation of ubiquitously present Epstein-Barr virus (EBV) is known to be involved with numerous diseases, including neurological ailments. A recent in vitro study from our group unveiled the association of EBV and its 12-amino acid peptide glycoprotein M146-157 (gM146-157) with neurodegenerative diseases, viz., Alzheimer's disease (AD) and multiple sclerosis. In this study, we have further validated this association at the in vivo level. The exposure of EBV/gM146-157 to mice causes a decline in the cognitive ability with a concomitant increase in anxiety-like symptoms through behavioral assays. Disorganization of hippocampal neurons, cell shrinkage, pyknosis, and apoptotic appendages were observed in the brains of infected mice. Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were found to be elevated in infected mouse brain tissue samples, whereas TNF-α exhibited a decline in the serum of these mice. Further, the altered levels of nuclear factor-kappa B (NF-kB) and neurotensin receptor 2 affirmed neuroinflammation in infected mouse brain samples. Similarly, the risk factor of AD, apolipoprotein E4 (ApoE4), was also found to be elevated at the protein level in EBV/gM146-157 challenged mice. Furthermore, we also observed an increased level of myelin basic protein in the brain cortex. Altogether, our results suggested an integral connection of EBV and its gM146-157 peptide to the neuropathologies.

New insights in the pathogenic mechanism of multiple sclerosis: Is Epstein-Barr virus associated with optic nerve involvement?

There are no reports in the literature studying the possible relationship between Epstein-Barr virus (EBV) and optic nerve involvement in multiple sclerosis (MS). The aim of our study was to analyze the association between EBV antibodies titres and optical coherence tomography (OCT) and OCT angiography (OCTA) quantitative parameters. We conducted a retrospective study. The study included 98 eyes of 49 patients with MS. Years of MS duration, relapse count, history of optic neuritis (ON), and immunoglobulin (Ig) G antibodies to the EBV viral capsid antigen (VCA) were recorded from each patient. Also, OCT analysis (including retinal nerve fibre layer (RNFL) thickness and ganglion cell-inner plexiform layer (GCIPL) thickness) and OCTA analysis (including perfusion density (PD) and flux index (FI) of the radial peripapillary capillary plexus) were performed in each participant. No significant associations were observed between anti-EBV antibody levels and OCT or OCTA parameters (p > 0,05). Correlation analysis between OCT and OCTA measurements showed a significant positive correlation between RNFL thickness and GCIPL thickness with peripapillary PD and FI (p < 0,035). Subgroup analysis revealed a significant diminution of RNFL thickness, GCIPL thickness and peripapillary PD and FI (p < 0,05) in the ON group. We were unable to demonstrate a significant association between anti-EBV VCA IgG antibody titres and OCT or OCTA parameters. Nonetheless, further longitudinal studies are needed to explore the possible association of EBV with optic nerve involvement in MS.

Tumor microenvironment in Hodgkin lymphoma: novel prognostic factors for assessing disease evolution.

Hodgkin lymphoma (HL) has become one of the most curable hematological neoplasia. Clinical and biological factors remain the main pillars guiding therapeutic strategies in HL. Recent studies have improved our understanding of the phenotype, the characteristics of histogenesis, and other possible mechanisms of lymphomagenesis, including the role of Epstein-Barr virus (EBV) infection. Tumor cells manipulate the microenvironment, allowing them to develop their malignant phenotype and evade the attack of the host's immune response so that the interaction between tumor cells and the reactive microenvironment determines not only the histological features but also the clinical-pathological characteristics and prognosis of these patients - essential for the development of future therapies targeting various other cellular components of the tumor microenvironment. This article aimed to evaluate the characteristics of the tumor microenvironment and malignant cells using histopathology and immunohistochemistry (IHC) techniques to highlight the association of EBV and to study the expression of characteristic antigens in malignant and non-malignant cells within the tumor mass (overexpression of BCL2 (B-cell lymphoma 2) in malignant cells, presence of PD1 (Programmed cell death Protein 1) on T lymphocytes, CD68+ macrophages in the tumor microenvironment, and presence of EGFR (epidermal growth factor receptor). The analysis of the data collected in this paper highlights several key parameters with prognostic value and statistical significance: the EBV infection at diagnosis, its association with low-intensity BCL2(+), the presence of CD68 with rosette formation, and the identification of specific vascularization patterns. The development of prognostic systems that take into account the integration of biological prognostic markers seems essential for a better risk stratification.

Incidence and association of high-risk HPVs and EBV in patients with advanced stages of colorectal cancer from Qatar

ABSTRACT High-risk Human Papillomaviruses (HPVs) and Epstein – Barr virus (EBV) are present and involved in several types of human carcinomas, including cervical and, head and neck cancers. Nevertheless, their presence and association in the pathogenesis of colorectal cancer is still nascent. The current study explored the association between the high-risk HPVs and EBV and tumor phenotype in colorectal cancers (CRCs) in the Qatari population. We found that high-risk HPVs and EBV are present in 69/100 and 21/100 cases, respectively. Additionally, 17% of the cases showed a copresence of high-risk HPVs and EBV, with a significant correlation only between the HPV45 subtype and EBV (p = .004). While the copresence did not significantly associate with clinicopathological characteristics, we identified that coinfection with more than two subtypes of HPV is a strong predictor of advanced stage CRC, and the confounding effect of the copresence of EBV in such cases strengthens this association. Our results indicate that high-risk HPVs and EBV can co-present in human CRCs in the Qatari population where they could plausibly play a specific role in human colorectal carcinogenesis. However, future studies are essential to confirm their copresence and synergistic role in developing CRCs.

Elevated PD-L1 Expression and Microsatellite Instability in Elderly Patients With Gastric Cancer.

Immunotherapy in combination with chemotherapy is the current treatment of choice for frontline programmed cell death ligand 1 (PD-L1)-positive gastric cancer. However, the best treatment strategy remains an unmet medical need for elderly or fragile patients with gastric cancer. Previous studies have revealed that PD-L1 expression, Epstein-Barr virus association, and microsatellite instability-high (MSI-H) are the potential predictive biomarkers for immunotherapy use in gastric cancer. In this study, we showed that PD-L1 expression, tumor mutation burden, and the proportion of MSI-H were significantly elevated in elderly patients with gastric cancer who were older than 70 years compared with patients younger than 70 years from analysis of The Cancer Genome Atlas gastric adenocarcinoma cohort [≥70/<70: MSI-H: 26.8%/15.0%, P =0.003; tumor mutation burden: 6.7/5.1 Mut/Mb, P =0.0004; PD-L1 mRNA: 5.6/3.9 counts per million mapped reads, P =0.005]. In our real-world study, 416 gastric cancer patients were analyzed and showed similar results (≥70/<70: MSI-H: 12.5%/6.6%, P =0.041; combined positive score ≥1: 38.1%/21.5%, P <0.001). We also evaluated 16 elderly patients with gastric cancer treated with immunotherapy and revealed an objective response of 43.8%, a median overall survival of 14.8 months, and a median progression-free survival of 7.0 months. Our research showed that a durable clinical response could be expected when treating elderly patients with gastric cancer with immunotherapy, and this approach is worth further study.

Nuclear respiratory factor 1 promotes the progression of EBV-associated gastric cancer and maintains EBV latent infection.

This study aimed to investigate the association of Epstein-Barr virus (EBV) with nuclear respiratory factor 1 (NRF1) and the biological function of NRF1 in EBV-associated gastric cancer (EBVaGC). Western blot and qRT-PCR were used to assess the effect of latent membrane protein 2A (LMP2A) on NRF1 expression after transfection with LMP2A plasmid or siLMP2A. The effects of NRF1 on the migration and apoptosis ability of GC cells were investigated by transwell assay and flow cytometry apoptosis analysis in vitro, respectively. In addition, we determined the regulatory role of NRF1 in EBV latent infection by western blot and droplet digital PCR (ddPCR). LMP2A upregulated NRF1 expression by activating the NF-κB pathway. Moreover, NRF1 upregulated the expression of N-Cadherin and ZEB1 to promote cell migration. NRF1 promoted the expression of Bcl-2 to increase the anti-apoptotic ability of cells. In addition, NRF1 maintained latent infection of EBV by promoting the expression of the latent protein Epstein-Barr nuclear antigen 1 (EBNA1) and inhibiting the expression of the lytic proteins. Our data indicated the role of NRF1 in EBVaGC progression and the maintenance of EBV latent infection. This provided a new theoretical basis for further NRF1-based anti-cancer therapy.

EBV Association with Lymphomas and Carcinomas in the Oral Compartment.

Epstein-Barr virus (EBV) is an oncogenic human herpesvirus infecting approximately 90% of the world's population. The oral cavity serves a central role in the life cycle, transmission, and pathogenesis of EBV. Transmitted to a new host via saliva, EBV circulates between cellular compartments within oral lymphoid tissues. Epithelial cells primarily support productive viral replication, while B lymphocytes support viral latency and reactivation. EBV infections are typically asymptomatic and benign; however, the latent virus is associated with multiple lymphomas and carcinomas arising in the oral cavity. EBV association with cancer is complex as histologically similar cancers often test negative for the virus. However, the presence of EBV is associated with distinct features in certain cancers. The intrinsic ability of EBV to immortalize B-lymphocytes, via manipulation of survival and growth signaling, further implicates the virus as an oncogenic cofactor. A distinct mutational profile and burden have been observed in EBV-positive compared to EBV-negative tumors, suggesting that viral infection can drive alternative pathways that converge on oncogenesis. Taken together, EBV is also an important prognostic biomarker that can direct alternative therapeutic approaches. Here, we discuss the prevalence of EBV in oral malignancies and the EBV-dependent mechanisms associated with tumorigenesis.

Plasma EBV DNA Methylation: Evidence of EBV Lytic Infection in HIV(+) EBV(+) Plasmablastic Lymphoma

Background: Among people living with HIV, plasmablastic lymphoma (PBL) and classical Hodgkin lymphoma (HL) are almost uniformly associated with Epstein-Barr virus (EBV). Immunohistochemical studies have demonstrated high levels of lytic gene expression in PL,1 whereas EBV(+) HL shows exclusively latent viral gene expression. EBV virion DNA is never CpG methylated, but tumor-derived plasma EBV is CpG methylated as previously shown by our group in EBV(+) HL and nasopharyngeal carcinoma (NPC).2 Others have also presented evidence that patterns of CpG methylation of plasma EBV DNA varies between people with NPC and non-malignant EBV(+) conditions.3 To better characterize the nature of plasma EBV in patients with lymphoma, we investigated EBV DNA copy number and EBV DNA methylation in HIV-associated PBL and HL. Methods: With appropriate approvals from the Human Research Ethics Committee of the University of the Witwatersrand and the Johns Hopkins Institutional Review Boards, we collected plasma from newly diagnosed untreated patients with HIV and PBL or HL in Johannesburg, South Africa. Diagnostic biopsy specimens were reviewed in Baltimore by a hematopathologist to confirm the diagnosis and Epstein-Barr encoding region (EBER) in situ hybridization was performed to determine EBV association. Plasma EBV copies were measured by standard qPCR targeting the BamW repeats. qPCR using the same primers was also performed after capture with methyl-DNA binding protein 2 (MBD2) magnetic beads, where the captured fraction represents methylated DNA and the flow-through represents unmethylated DNA. Results: We studied plasma from 7 patients with PBL and 12 patients with HL. Four of five PBL tumors were EBV (+) and eight of 10 HL tumors were EBV (+) by tissue EBER in situ hybridization. Analysis of plasma EBV DNA copy number showed overlapping levels of EBV DNA (median 2.7 Log10 copy/mL in PBL and 3.2 Log10 copy/mL in HL) (Fig. 1). Patients with at least 1.5 Log10 copy/mL of EBV underwent CpG methylation evaluation, which showed very different EBV CpG methylation indices. The EBV methylation index was highly variable in PBL (median of 51%) and was uniformly high in HL (median of 97%). Conclusions: Although plasma from plasmablastic lymphoma patients show high EBV copy number, the characteristic of that EBV DNA is very different from the plasma EBV detected in Hodgkin lymphoma patients. This difference is hypothesized to be related to evidence of viral lytic gene expression seen in PBL. The degree of plasma EBV DNA methylation may have broad implications for lymphoma diagnosis and subtyping.

ABCL-542 Prevalence and Characterization of EBV-Negative Post-Transplant Lymphoproliferative Disorder

A common and potentially fatal post-solid organ transplant (SOT) complication is post-transplant lymphoproliferative disorder (PTLD). While the association of Epstein-Barr virus (EBV) with the development of PTLD is well recognized, little is known about the etiology of EBV-negative PTLD. To characterize the differences between EBV-positive and EBV-negative PTLD to better understand the pathogenesis of EBV-negative PTLD. This was a retrospective study that reviewed patients who developed PTLD after SOT. Data was collected on PTLD patients (>18 years) from 2011 to 2021. Data included demographics, SOT type, time from SOT to PTLD development, tumor EBV status, PTLD site, histopathological morphology, tumor markers, and overall survival. EBV tumor status was compared using χ2, Fisher's Exact, and Wilcoxon Rank Sum tests. A single, large academic center. A total of 99 patients met the inclusion criteria. Of those, 45.5% were EBV-positive and 54.5% were EBV-negative. Tumor EBV status did not differ by race, but males were more likely to be EBV-negative (63% v. 44.4% of females, p=0.065). EBV tumor status did not differ by SOT type. The interval between SOT and PTLD diagnosis was longer in EBV-negative patients (8.68 years) than EBV-positive patients (4.93 years) (p=0.001). There was a significant difference in EBV-negative PTLD site (p=0.046) and PTLD subtypes (p=0.002). Site of EBV-negative PTLD consisted of gastrointestinal (38.9%), head/neck (11.1%), liver/spleen (11.1%), CNS (3.7%), other lymph (24%), and other non-lymph (11.1%). Monomorphic (65.5%) and T-cell (90%) subtypes were more common in EBV-negative patients, compared to the polymorphic (15.4%) and plasmablastic/plasmacytic (27.3%) subtypes. Expression of CD20 did not differ by tumor EBV status. Those who were CD30-negative were more likely to be EBV-negative (90% v. 25%, p=<0.001). Those who were CD138-negative were more likely to be EBV-negative (75% v. 26.7%, p=0.012). There was no difference in overall survival by tumor EBV status. This single institution retrospective review shows that there are distinct differences between EBV-negative and EBV-positive PTLD. EBV-negative PTLD has a longer interval from SOT to PTLD development, is more likely to occur in the gastrointestinal tract, and is more likely to have a monomorphic morphology.

Detection of Epstein-Barr virus in systemic sclerosis patients: A molecular and serological based study.

This study aimed to evaluate an association between Epstein-Barr virus (EBV) and systemic sclerosis (SSc). One hundred and fifty (138 female, 12 male) consecutive adult SSc patients fulfilling the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria were included in this cross-sectional study. Serological analysis by line blot for class immunoglobulin G (IgG) and IgM antibodies against EBV antigen (EBV capsid antigen [VCA] gp125, VCA p19, EBNA-1, p22, EA-D) and quantification of EBV DNA in whole blood by real-time polymerase chain reaction was performed. Class IgM antibodies against VCA gp125 (22.8% vs 0%, P < .0002), VCA p19 (55.7% vs 4.4%, P < .0001), EBNA1 (35.7% vs 0%, P < .0001), p22 (24.2% vs 0%, P < .0001), EA-D (14.2% vs 2.2%, P < .04), and class IgG antibodies against p22 (95.7% vs 82.2%, P < .02) and EA-D (54.2% vs 0%, P < .0001) reactivities were significantly higher in SSc patients than in controls. The past infection was significantly associated with the control group (42.8% vs 91%, P < .0001); and the viral reactivation was significantly associated with the SSc group (55.7% vs 4.4%, P < .0001). Only three (2%) out of 150 SSc patients were positive for EBV DNA, similar to the control group (2%) (P > .9). The study shows a strong serological association of EBV (reactivation stage) with SSc patients in the absence of viral DNA in the circulation, indicating the EBV reservoir or tropism presence elsewhere.

Herpesvirus Screening in Childhood Hematopoietic Transplant Reveals High Systemic Inflammation in Episodes of Multiple Viral Detection and an EBV Association with Elevated IL-1β, IL-8 and Graft-Versus-Host Disease.

Infections remain a major cause of morbidity and mortality among hematopoietic stem cell transplant (HSCT) recipients. Unlike Epstein–Barr Virus (EBV) and Human Cytomegalovirus (HCMV), Human Herpesvirus (HHV) 6, HHV7 and HHV8 are not routinely monitored in many centers, especially in the pediatric population of low–medium income countries. We screened EBV, HCMV, HHV6, HHV7 and HHV8 in 412 leukocytes-plasma paired samples from 40 pediatric patients assisted in a tertiary hospital in Mexico. Thirty-two underwent allo-HSCT, whereas eight received auto-HSCT. Overall viral detection frequencies in allo- and auto-HSCT were: EBV = 43.7% and 30.0%, HCMV = 5.0% and 6.7%, HHV6 = 7.9% and 20.0% and HHV7 = 9.7% and 23.3%. HHV8 was not detected in any sample. Interestingly, HHV6 and HHV7 were more frequent in auto-HSCT, and HHV6 was observed in all episodes of multiple detection in auto-HSCT patients. We found EBV DNA in plasma samples, whereas HCMV, HHV6 and HHV7 DNA were predominantly observed in leukocytes, indicative of their expansion in cellular compartments. We also found that IL-1β, IL-2, IL-6 and IL-8 were significantly increased in episodes in which multiple viruses were simultaneously detected, and samples positive for EBV DNA and graft-versus-host disease had a further increase of IL-1β and IL-8. In conclusion, the EBV, HCMV, HHV6 and HHV7 burdens were frequently detected in allo- and auto-HSCT, and their presence associated with systemic inflammation.

Follicular dendritic cell sarcoma of gastrointestinal tract with two emerging distinct subtypes: a case report and systemic review

BackgroundFollicular dendritic cell sarcoma (FDCS) is a rare neoplasm of mesenchymal origin. FDCS of gastrointestinal tract (GI) are exceedingly uncommon.Case presentationWe report the first case of classic type FDCS in a 34-year-old male with Birt-Hogg-Dubé syndrome, which presented as a mass at the ileo-cecal junction. He received no further treatment after resection and remained disease free for 3.5 years. We further analyze and review the clinical and pathologic findings of 33 cases of GI tract FDCS reported in the literature.ConclusionsThere are two distinct subtypes of FDCS in the GI tract: the classic type occurs in relatively younger patients (mean = 45.3 years) without Epstein-Barr virus (EBV) association, and behaves more aggressively; the inflammatory subtype presents as colonic polypoid tumor in older patients (mean = 60.7 years) and is EBV positive. The clinical outcome in the latter group appears favorable although mortality rate is not necessarily low.

PCR Detection of Epstein-Barr Virus (EBV) DNA in Patients with Head and Neck Squamous Cell Carcinoma, in Patients with Chronic Tonsillitis, and in Healthy Individuals.

Epstein-Barr virus (EBV) is a common virus worldwide that is an etiologic agent in the development of many diseases, including cancer. Recent reports have shown the association of EBV with tumorigenesis in head and neck squamous cell carcinoma (HNSCC). Moreover, EBV has been reported to be present in tonsillar tissues, which suggests a close relationship between viral infections and tonsillar diseases, including chronic tonsillitis. The aim of the study was to analyze the prevalence of EBV DNA in 86 patients with HNSCC, in 70 patients with chronic tonsillitis, and in 144 healthy individuals (control group) and the associations between EBV infection and clinicopathological and demographic characteristics and the use of stimulants in all study groups. The objective of this study was also to analyze the prevalence of coinfection with human papillomavirus (HPV). After prior DNA isolation, EBV detection was performed using an EBV kit by real-time polymerase chain reaction. The prevalence of EBV infection in patients with HNSCC, patients with chronic tonsillitis, and the control group was 47.7%, 60%, and 24.3%, respectively. Compared to controls, a significantly higher prevalence of EBV in patients with chronic tonsillitis and HNSCC may suggest that EBV is a potential risk factor. No association was found between EBV infection and demographic or clinical data. Further studies are warranted due to inconclusive reports that were mainly related to geographic distribution, sample type, and detection technique. Considering the prevalence of the virus and the risk of serious diseases, attention should be paid to screening diagnosis and prevention of the infection.

The Association of Epstein-Barr Virus With Cancer.

Epstein-Barr virus (EBV) is classified as a herpesvirus and is known for being one of the few viruses that can lead to the development of cancer. This study has gathered several studies to provide evidence as to this association as well as some of the mechanisms specific to EBV that allow this to happen. The development of EBV into cancer as well as the proteins involved in this oncogenesis play a crucial role in understanding this problem as well as creating a solution for mitigating this disease process in the future. This study summarized three of the most common malignancies caused by EBV in order to consolidate information about each of them. Additional emphasis was placed on finding which EBV serum markers were seen to be most indicative of prognosis and likelihood of developing malignancy. Higher serum EBV viral DNA loads were seen to be a useful indicator in assessing the risk of various cancers and should be studied further in relation to cancers that were not mentioned in this review.

Epstein-Barr Virus Association with Breast Cancer: Evidence and Perspectives.

Simple SummaryEpstein–Barr virus (EBV) is a very ubiquitous and persistent virus present in ~90% of the world population. The infection is generally asymptomatic during the lifetime, though it can cause lymphoid tumors and carcinomas in some subjects. The role of EBV in breast cancer (BC) has yet to be determined. In this review, we present the historical background and scientific evidence regarding the presence and potential role of EBV in this malignancy and we propose possible molecular mechanisms. Knowledge of EBV´s role in BC will contribute to establishing prevention strategies, early detection, and control of this highly aggressive and prevalent malignancy.Epstein–Barr virus (EBV) is an enveloped DNA virus that belongs to the gamma Herpesviridae family. The virus establishes a latent/lytic persistent infection, though it can be involved in cancer development in some subjects. Indeed, evidence supports an etiological role of EBV in undifferentiated nasopharyngeal carcinoma (NPC), a subset of gastric carcinomas and lymphomas. Additionally, EBV has been detected in breast carcinomas (BCs) although its role has not been established. In this review, we summarize epidemiological information regarding the presence of EBV in BC and we propose mechanistic models. However, additional epidemiological and experimental evidence is warranted to confirm these models.

Epstein-Barr virus-based nasopharyngeal carcinoma population screening

: Nasopharyngeal carcinoma (NPC) is characterized by its distinct geographical distribution and has a high incidence in southern China and Southeast Asia. Early diagnosis and treatment are the best strategies for individuals identified to have a high risk of NPC. The identification of high-risk populations and the use of appropriate screening methods are key factors when screening for NPC. Despite the discovery of the close association of Epstein-Barr virus (EBV) with NPC, the exact role of the virus in the development of NPC has not been completely elucidated. EBV serological antibody testing is of great significance while screening for NPC, and plasma EBV-DNA has been used for population screening. The screening also includes clinical examination (lymphatic palpation and indirect examination of the nasopharynx using a mirror) and obtaining the family history of patients with NPC. The main secondary screening methods include nasopharyngeal fiberscopy. Another approach to diagnose NPC includes cytological examination of the nasopharyngeal brush exfoliates. Evidence suggests that serological screening for NPC can increase the rate of early diagnosis and significantly improve the 5-year survival rate of the affected population. However, the NPC serological screening protocol has some shortcomings. For example, the positive predictive value needs to be improved. Further research into NPC should be focused on methods that will accurately identify high-risk individuals and optimize screening. Here, we have reviewed the latest progress in EBV-based NPC population screening.

Особенности вирусных энцефалитов у детей по данным Киевской городской детской клинической инфекционной больницы с 2011 по 2016 год

Проведен ретроспективный анализ 46 историй болезни детей, находившихся на стационарном лечении в Киев­ской городской детской клинической инфекционной больнице с 2011 по 2016 год. Была проанализирована этиология энцефалита у детей в зависимости от возраста и выявлено, что в этиологии вирусного энцефалита у детей первых 3 лет жизни преобладали цитомегаловирус и ассоциация Эпштейна — Барр вируса (EBV) с цитомегаловирусом — по 25 %. У подростков в этиологии превалировали EBV — 31 % и герпесвирус (HHV) 6-го типа — 31 %. У детей в возрасте 3–6 лет в этиологии преобладал EBV — 30 %, у детей 6–12 лет — HHV 6-го типа и EBV — по 27 %. В клинической картине энцефалита у подростков преобладал общемозговой синдром, а у детей первых 3 лет жизни — общеинфекционный. Очаговая неврологическая симптоматика отмечалась у больных всех возрастных групп. У детей старшего возраста начальными проявлениями заболевания были головная боль, недомогание, тошнота, рвота, у детей первых трех лет жизни — сонливость, раздражительность и отказ от еды. Частыми очаговыми симптомами у детей были афазия, атаксия, парезы, параличи, миоклонии.

Nasopharyngeal cancer: Incidence and prognosis of human papillomavirus and Epstein-Barr virus association at a single North American institution.

The prognostication of Epstein-Barr virus (EBV) and human papillomavirus (HPV) status in nasopharyngeal cancer (NPC) is unclear. This retrospective study analyzed NPC from 2000 to 2019. Seventy-eight patients were included: 43 EBV+ , 12 HPV+ , 23 EBV- /HPV- , and 0 EBV+ /HPV+ . All p16+ tumors were also positive for HPV-CISH. Baseline characteristics were not different between groups except age, N-classification, and Karnofsky Performance Scale (KPS) (p < 0.05). For EBV+ , HPV+ , and EBV- /HPV- respectively, 3-year overall survival (OS) was 89.9%, 69.8%, and 52.5% (p=0.006). EBV- /HPV- status was significantly associated with worse OS but not freedom from progression (FFP) on univariate analysis, and did not remain a significant predictor of OS after adjusting for KPS, age, and group stage. EBV+ NPC tumors were seen in younger, healthier patients than HPV+ and EBV- tumors, and there were no cases of coinfection. The association of viral status with OS was insignificant after adjusting for KPS and age.