The complex Epstein-Barr virus: Understanding its systemic impact and oral implications

The Epstein-Barr virus (EBV) is a member of the herpesvirus family and one of the most common human viruses globally. Recognized as the first human tumor virus, EBV was discovered in 1964 by Sir Anthony Epstein and Yvonne Barr. It is estimated that at least 95% of the world’s population carries EBV. Most individuals become infected during childhood without symptoms; however, it is during adolescent and adult years that infection causes symptoms.

EBV is known for its association with a wide range of diseases spanning from benign conditions to various forms of cancer. It is best known for infectious mononucleosis, but EBV’s impact also extends to raise the risk for chronic conditions, autoimmune disorders, and even periodontal and oral diseases.¹ The purpose of this article is to explore the nature of EBV, revealing some of its diseases, outlining the relation to periodontal and oral conditions, and discussing the current state of vaccination efforts.

EBV is a double-stranded DNA B-lymphotropic herpesvirus that is transmitted mostly through saliva. It is a lifelong virus that results in the risk of lifelong infection.² Commonly, it is nicknamed the “kissing disease” when discussing infectious mononucleosis.³ The virus has a complex life cycle that includes an initial infection; a lytic phase, which leads to the production of infectious viruses in both B cells and epithelial cells; a latent phase, where the virus resides hidden in the host’s B cells; and potential reactivation periods. Classified as a group I carcinogen, EBV is linked to 1.5% of all human malignancies and 1.8% of all cancer-related deaths that include Burkitt’s lymphoma; Hodgkin’s lymphoma; B-cell, T-cell, and NK-cell lymphoma; gastric carcinoma; and nasopharyngeal carcinoma.⁴

Diseases and cancers

Infectious mononucleosis (mono) is likely the most well-known condition associated with EBV. Commonly occurring in approximately 25% of adolescents and young adults who contract EBV, mono is characterized by symptoms such as sudden fever, severe sore throat, lymphadenopathy, and extreme fatigue. After the acute infection, the virus stays latent in the B lymphocytes for the rest of the life of the host.³ The disease is typically self-limiting, although the symptoms can last for several weeks and, in rare cases, even months. Diagnosis is usually based on symptoms, and treatment is usually over-the-counter medications for fever, pain control, and comfort.

Burkitt’s lymphoma (BL) is a highly aggressive B-cell malignancy among non-Hodgkin’s lymphoma that has a direct link to EBV. There are three types of BL: endemic (African), sporadic (non-African), and immunodeficiency associated. The endemic form often presents with jaw lesions in African children, whereas the sporadic form often presents with abdominal masses.² Human immunodeficiency virus (HIV)-associated BL mainly occurs with HIV infection. There has been an increase in EBV-dependent BL in adult populations due to the increased adult cases of HIV in all countries of the world.²

Nasopharyngeal carcinoma (NPC) is a malignancy arising from the epithelial cells of the nasopharynx. NPC accounts for 82% of EBV-attributed malignancies and is implicated particularly in individuals from Southeast Asia.⁴ Through EBV’s ability to induce genetic mutations and promote cellular proliferation, it contributes to the three different histological types of NPC. Type 1 is a keratinizing squamous cell carcinoma, type 2 is nonkeratinizing squamous cell carcinoma, and type 3 is an undifferentiated carcinoma. The prevalence of EBV has a 100% detection in types 2 and 3 NPC.⁴

In 2018, gastric carcinoma was reported to be the fifth most common cancer and the third cause of cancer death around the globe. By way of B lymphocytes in the oropharyngeal lymphoid tissue, EBV enters the gastric epithelial cells in a latency phase. In a meta-analysis of 30 case-control studies from 26 different countries, EBV indicated a significant association with gastric cancers.⁵

Relation to autoimmune diseases

Multiple sclerosis (MS), characterized by demyelination of neurons in the brain and spinal cord, is the most prevalent autoimmune disease of the central nervous system. More than 400,000 people in the US and over two million worldwide are affected by this debilitating disorder. Common symptoms of MS include impaired motor function, fatigue, visual disorders, and ataxia. MS can also lead to deafness and dementia.^2,6 Currently, there are ongoing clinical studies that aim to identify a possible relationship between EBV as a risk factor for MS.⁶

Other autoimmune disorders such as Sjögren’s syndrome, rheumatoid arthritis, lupus, and chronic fatigue syndrome have all been examined closely and tested for high seroepidemiological associations of antibodies to EBV. Overwhelmingly, the studies show a link to EBV and these autoimmune disorders. More research will be done to identify the pathophysiology and significance of these associations.^7-10

Relationship of Epstein-Barr virus to oral conditions

Because periodontal disease is opportunistic, it is noted that EBV could act as a cofactor by modulating the host’s immune response. The virus’s presence in the oral cavity and periodontal tissues could potentially exacerbate inflammation and contribute to the progression of periodontal disease. Studies have detected EBV DNA in periodontal tissues of patients with severe periodontitis, coupled with increased inflammatory cytokines, suggesting that the virus may play a role in disease exacerbation or persistence.¹¹

Chronic periodontitis (CP) is considered to have a bacterial onset and is one of the most prevalent diseases globally. It has been proven to have a direct relationship with certain systemic diseases such as diabetes mellitus; however, recent research now suggests a potential link between EBV and periodontal disease through higher amounts of EBV DNA discovered in the crevicular fluid of people with CP versus those without periodontitis. The prevalence of EBV is also shown to have a correlation with increased pocket depth.^11,12

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer that is directly associated with tobacco smoking and alcohol consumption.³ EBV, associated with cancer, is shed in the saliva and lives in the oral cavity. EBV is implicated in several OSCCs, although the potential role of the virus has yet to be learned.¹³

Vaccination update

Despite extensive research, there is no available vaccine specifically for EBV. Efforts to develop an EBV vaccine have been challenging due to the virus’s complex biology and the diversity of its effects on the immune system. The fact that the virus has a latency stage and can go hidden and undetected for years makes it difficult for researchers to identify a single effective target for vaccination. In 2024, the National Institutes of Health published that scientists may have found a weak point on the virus that may allow a vaccine or antibody-based treatment to block the ability of EBV to bind to the B lymphocyte cells.¹

Conclusion

EBV is a complex pathogen that negatively affects human health. With an overwhelming amount of research suggesting involvement with so many illnesses, autoimmune diseases, cancers, and oral conditions, EBV’s impact is profound and multifaceted. While there is no vaccine currently available, ongoing research aims to address the challenges of vaccine development and improve prevention and treatment strategies. Understanding EBV’s role in both common and rare conditions is crucial for advancing medical knowledge and improving patient outcomes. 

Editor's note: This article appeared in the July 2025 print edition of RDH magazine. Dental hygienists in North America are eligible for complimentary print subscription. Sign up here.

References

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