Endocrine-immune interactions in Hashimoto’s thyroiditis and human papillomavirus-induced cervical cancer: The role of Epstein-Barr, hepatitis C, and hepatitis D viruses in shared pathogenesis
2026· Vojnosanitetski Pregled· pp. 46-46· 0 citations
TL;DR
Current evidence remains insufficient to confirm a direct association between HT and an increased risk of developing CC, and further experimental and epidemiological studies are required to elucidate the potential relationship between HT and HPV-induced CC.
Abstract
Hashimoto’s thyroiditis (HT) and human papillomavirus (HPV)-induced cervical cancer (CC) are distinct clinical entities; however, their etiologies share several pathogenetic mechanisms related to immune dysregulation, endocrine disturbances, and chronic inflammation. HT is an autoimmune disease characterized by lymphocytic infiltration of the thyroid gland, autoantibody production, and progressive tissue damage resulting from a persistent inflammatory response. In contrast, the development of HPV-induced CC depends on the virus’s ability to evade host immune surveillance, thereby enabling long-term persistence of the infection. Increasing evidence suggests a potential role of other viral infections, particularly Epstein-Barr virus and hepatitis C virus, in the development of autoimmune thyroid diseases. The underlying mechanisms include chronic inflammation, molecular mimicry, and impaired immune tolerance. Furthermore, thyroid hormones and the sex hormones estrogen and progesterone play a significant role in modulating innate and adaptive immune responses and may influence the persistence of viral infections. Although there is an overlap in the immunological and endocrine mechanisms involved in these conditions, current evidence remains insufficient to confirm a direct association between HT and an increased risk of developing CC. Further experimental and epidemiological studies are required to elucidate the potential relationship between HT and HPV-induced CC.
Behçet’s disease is a chronic, relapsing multisystem inflammatory disorder characterized by recurrent oral and genital ulcerations, ocular inflammation, cutaneous lesions, and variable involvement of the vascular, neurological, and gastrointestinal systems. Although its precise etiology remains incompletely understood, accumulating evidence indicates that the disease arises from a complex interplay between genetic susceptibility, immune dysregulation, and environmental triggers. Among the proposed infectious agents, herpes simplex virus (HSV) has attracted considerable attention because of its capacity to induce persistent immune activation, molecular mimicry, and chronic inflammatory responses. Accordingly, the present study aimed to evaluate the expression profiles of HSV-related genes (UL29, UL18, UL46, and UL47) in peripheral blood leukocytes of patients with Behçet’s disease to clarify the potential contribution of HSV infection to disease pathogenesis and immune-mediated inflammatory mechanisms. In this case-control study, 40 patients with BD and 40 healthy individuals were included as the control group. Blood samples were collected from all participants. Total RNA was extracted from peripheral blood leukocytes, followed by cDNA synthesis. The expression levels of UL29, UL18, UL46, and UL47 genes were quantified using RT-qPCR. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic potential of the studied genes. Statistical analyses were conducted using GraphPad Prism and SPSS software (P-value ≤ 0.05). The expression of HSV-related genes was significantly higher in BD patients compared to healthy controls. After Bonferroni correction for multiple comparisons, UL29 remained significantly upregulated (4.5-fold, adjusted
p
= 0.012), while UL46 (3.7-fold, adjusted
p
= 0.060), UL18 (2.0-fold, adjusted
p
= 0.152), and UL47 (2.25-fold,
p
= 0.12) did not reach statistical significance. ROC curve analysis demonstrated strong diagnostic potential for UL29 (AUC = 0.90, sensitivity 80%, specificity 92.5%), UL46 (AUC = 0.86, sensitivity 87%, specificity 77.5%), and UL18 (AUC = 0.80, sensitivity 85%, specificity 72.5%). Overall, UL29, UL46, and UL18 showed promising potential as biomarkers for distinguishing BD patients from healthy individuals. Increased expression of UL29, UL46, and UL18 is associated with BD, and these genes, particularly UL29, show promising potential as diagnostic biomarkers. Further validation studies are needed.
Seyyedeh Maryam Rezvan Leilan, Shiva Ahmadishoar, M. Pashazadeh· Clinical and Experimental Me...· 0 citations
Epstein–Barr virus (EBV) is a ubiquitous herpesvirus, increasingly implicated in the pathogenesis of several autoimmune diseases, such as multiple sclerosis (MS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). These diseases have both, shared and disease-specific immunopathogenic pathways involving EBV. Shared mechanisms include the role of EBV latent proteins in triggering immune dysfunction, molecular mimicry between viral and self-antigens, infection of autoreactive B-cells, and dysfunction of type 1 interferon (IFN-1) responses. In MS, EBV is associated with a CNS-compartmentalized CD8+ T-cell responses, molecular mimicry with neural antigens, and formation of meningeal tertiary lymphoid structures. In SLE, EBV contributes to systemic autoimmunity through mimicry with multiple autoantigens, recurrent viral reactivation, and IFN-driven multi-organ inflammation. In RA, EBV promotes the formation of synovial ectopic lymphoid structures, enhances anti-citrullinated protein antibody production, and drives proinflammatory cytokine dysregulation. Host genetic variations, particularly in HLA alleles, further modulate susceptibility by influencing antigen presentation, viral control and autoreactive T-cell responses. Rather than acting as a uniform and consistent trigger, EBV appears to function as a context-dependent immunological modifier whose pathogenic effects are influenced by factors such as the timing of infection, tissue microenvironment, HLA-associated genetic background, and other environmental exposures. Unravelling the details of these mechanisms may inform targeted preventive and therapeutic strategies for EBV-associated autoimmune diseases.
Fathima Shabnam, Gulfaraz Khan· Frontiers in Immunology· 0 citations
Oral cavity (OC) and oropharyngeal (OP) squamous cell carcinoma (SCC) represent a major global health concern, accounting for most of head and neck malignancies. These tumors arise from the epithelial lining of the OC and oropharynx and are characterized by aggressive local invasion, lymph node metastasis, and high morbidity and mortality. In addition to known risk factors such as tobacco and alcohol consumption, several oncogenic viruses, including human papillomavirus (HPV), Epstein-Barr virus (EBV), human herpesviruses (HHV) 1 and 2, cytomegalovirus (CMV) and Merkel cell polyomavirus (MCPyV), have been implicated in the development, progression, or prognosis. Detection of viral genomes within tumor tissues suggests a complex interplay between viral oncogenes, host immune responses, and environmental factors in carcinogenesis. This systematic review synthesizes current evidence on the contribution of oncogenic viruses to the etiology of OC and OP SCC. Following the PRISMA 2020 guidelines, observational studies between January 2015 and December 2025 were identified through searches of PubMed, Scopus and Web of Science. Eligible studies were limited to human research and reporting viral detections. The results demonstrate a strong, consistent, and clinically relevant association between HPV infection and OP SCC, while evidence supporting a causal or prognostic role for non-HPV oncogenic viruses in OC and OP SCC remains limited and heterogeneous. Substantial methodological variability in viral detection approaches and epidemiological reporting was observed, underscoring the need for standardized assessment frameworks. Overall, these results support site-specific interpretation of viral oncogenesis and inform the development of targeted prevention, diagnostic stratification, and therapeutic strategies.
Juan Manuel Quiroga-Garza, M. F. Herrera-Saldivar, Norma Carolina Hernandez-Bautista et al.· Frontiers in Oncology· 0 citations
Autoimmune thyroid diseases (AITDs), including Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), affect approximately 2–5% of the global population. They are the most common organ-specific autoimmune disorders worldwide. Growing epidemiological and immunological evidence indicates that AITDs frequently coexist with immune-mediated dermatological diseases. These include atopic dermatitis (AD), psoriasis, alopecia areata (AA), vitiligo, and chronic spontaneous urticaria (CSU). Targeted immunotherapies have become central to the treatment of many immune-mediated skin diseases. Although these therapies are designed to act on specific immune pathways, they may also exert broader systemic immunomodulatory effects. However, thyroid function and thyroid autoantibodies are not routinely assessed in patients with immune-mediated dermatological conditions. This is also true for some patients with known or suspected AITDs. In this narrative review, we summarize the immunological overlap between cutaneous inflammation and autoimmune thyroid disease. We also discuss thyroid-related evidence for IL-4Rα inhibitors, IL-17 inhibitors, JAK inhibitors, IL-12/23 inhibitors, and immune checkpoint inhibitors (ICIs). Current evidence suggests that ICIs have the strongest established association with thyroid dysfunction. In contrast, the thyroid-related effects of dupilumab and ustekinumab are supported mainly by rare case reports. IL-17 inhibitors and selective IL-23p19 inhibitors may theoretically attenuate thyroid inflammatory pathways. However, this possibility has not yet been confirmed in clinical studies. Based on the available evidence, we propose a risk-stratified approach to thyroid surveillance across targeted immunotherapies. Routine thyroid monitoring is most strongly supported for ICIs. For patients at increased thyroid risk, selective assessment of thyroid function and thyroid autoantibodies may also be considered during treatment with dupilumab or ustekinumab. For oral JAK inhibitors, monitoring may be particularly relevant before treatment, during therapy, and after discontinuation because of the potential for immune rebound. Prospective studies are needed to define which patient subgroups would benefit most from thyroid surveillance during targeted immunotherapy.
A testable positive-feedback perspective in which thyrocyte ERS injury and immune effector amplification may mutually reinforce one another is proposed, in which thyrocyte ERS injury and immune effector amplification may mutually reinforce one another.
X. Si, Zhi-Xun Guo, Gena Jiao et al.· Frontiers in Immunology· 0 citations
Fulminant viral hepatitis (FVH) in children is a rare but often fatal form of acute liver failure occurring in the absence of preexisting liver disease. Its exceptional incidence during otherwise common viral infections, including hepatitis A virus (HAV), hepatitis B virus (HBV), and herpes simplex virus (HSV), supports a decisive role for host susceptibility. Recent advances in human immunogenetics delineate two major, mechanistically distinct pathways to pediatric FVH. The first reflects failure of immune regulation, culminating in excessive IFN-γ–driven inflammation and immune-mediated hepatocellular necrosis. Autosomal recessive IL-18BP and IL-10RB deficiencies exemplify this mechanism, in which disruption of key regulatory checkpoints permits uncontrolled activation of cytotoxic lymphocytes and macrophage-dependent immunopathology, particularly in the context of HAV infection. The second pathway involves impaired intrinsic antiviral defense, most prominently through neutralizing autoantibodies against type I interferons, which phenocopy genetic defects of IFN-I signaling and are strongly associated with HSV-triggered FVH; in this setting, inadequate early antiviral control enables unchecked hepatic replication with extensive cytopathic damage. Finally, syndromic hyperinflammatory disorders, including familial hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease, broaden the spectrum of immune predisposition in which fulminant hepatitis may arise. Together, these discoveries redefine pediatric FVH as an immunopathological syndrome and provide a framework for targeted genetic and serologic diagnosis and for mechanism-based interventions aimed at improving survival.
M. Bousfiha, Dalal Ben Sabbahia, E. Jouanguy et al.· Frontiers in Immunology· 0 citations