Search Results (12)

It is estimated that approximately 90% of all head and neck cancers are squamous cell carcinomas with a complex and multifactorial etiology. Molecular and epidemiological studies provide evidence for the role of oncogenic viruses in the initiation and/or oncomodulation of head and neck squamous cell carcinoma. Objectives: The present study aimed to detect the presence of high- and low-risk HPV, BKPyV, EBV, HCMV, HSVs in biopsy samples of squamous cell carcinoma of the external auricle in patients in Bulgaria. Materials and Methods: The study included 41 biopsy specimens from etiologically undiagnosed cases of squamous cell carcinoma of the external auricle. Molecular biological methods were used to detect the viruses—conventional and nested PCR, and sequence analysis. Results: The results obtained showed that none of the samples were found to have a high-risk HPV genotype. The highest percentage of samples showed genotype 6/11, and the lowest number of samples showed low-risk genotype 44. Of all herpesviruses, EBV was found in the largest proportion of samples, being present in the sample as a co-infection with HPV and always together with genotype 6/11. The frequency distribution, as a percentage and number of samples, of the possibilities for co-infection of EBV with each of the HPV genotypes was established. Of the remaining herpesviruses, the presence of HSV 2 was not confirmed in any of the samples. HSV 1 was present in only three of the samples, as a co-infection with genotypes 6/11, 42 and 43. When examining the samples for the presence of HCMV, only one positive sample was found, with both HPV 6/11 and 42 additionally present in the sample. Conclusions: For the first time, HPV, BKPyV, EBV, HCMV and HSVs were investigated and their possible involvement alone or as co-infection in the carcinogenesis of squamous cell carcinoma of the external auricle in patients in Bulgaria. The presence of the mentioned viruses, as well as the non-random distribution of EBV + HPV 6/11 and EBV + HPV 44, proven by us, does not necessarily make them etiological agents, but they could, through different and known mechanisms, influence the initiation and/or modulation of carcinogenesis. Full article

Salivary glands’ neoplasms are hard to diagnose and present a complex etiology. However, several viruses have been detected in these neoplasms, such as HCMV, which can play a role in certain cancers through oncomodulation. The co-infections between HCMV with betaherpesviruses (HHV-6 and HHV-7) and polyomaviruses (JCV and BKV) has been investigated. The aim of the current study is to describe the frequency of HCMV and co-infections in patients presenting neoplastic and non-neoplastic lesions, including in the salivary gland. Multiplex quantitative polymerase chain reaction was used for betaherpesvirus and polyomavirus quantification purposes after DNA extraction. In total, 50.7% of the 67 analyzed samples were mucocele, 40.3% were adenoma pleomorphic, and 8.9% were mucoepidermoid carcinoma. Overall, 20.9% of samples presented triple-infections with HCMV/HHV-6/HHV-7, whereas 9.0% were co-infections with HCMV/HHV-6 and HCMV/HHV-7. The largest number of co-infections was detected in pleomorphic adenoma cases. All samples tested negative for polyomaviruses, such as BKV and JCV. It was possible to conclude that HCMV can be abundant in salivary gland lesions. A high viral load can be useful to help better understand the etiological role played by viruses in these lesions. A lack of JCV and BKV in the samples analyzed herein does not rule out the involvement of these viruses in one or more salivary gland lesion subtypes. Full article

Epstein–Barr virus (EBV), Kaposi sarcoma human virus (KSHV), human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), human T-lymphotropic virus-1 (HTLV-1), and Merkel cell polyomavirus (MCPyV) are the seven human oncoviruses reported so far. While traditionally viewed as a benign virus causing mild symptoms in healthy individuals, human cytomegalovirus (HCMV) has been recently implicated in the pathogenesis of various cancers, spanning a wide range of tissue types and malignancies. This perspective article defines the biological criteria that characterize the oncogenic role of HCMV and based on new findings underlines a critical role for HCMV in cellular transformation and modeling the tumor microenvironment as already reported for the other human oncoviruses. Full article

Background: Human cytomegalovirus (HCMV) is increasingly suggested to be involved in human carcinogenesis and onco-modulation due to its ability to contribute to all hallmarks of cancer. Growing evidence demonstrates a link between HCMV infection and various malignancies, including breast cancer, which incidence and mortality are still on the rise. The etiology of breast cancer remains mostly unclear, leaving 80% of breast cancer cases considered to be sporadic. Identifying novel risk- and prognostic factors for improved breast cancer treatment and increased survival rates, were the objectives of this study. Methods: Automated immunohistochemical staining results for HCMV proteins in 109 breast tumors and lymph node metastasis were correlated with clinical follow-up data (>10 years). Statistical analyses for median Overall Survival (OS) were performed. Results: Survival analyses revealed shorter median OS for patients with HCMV-IE positive tumors of 118.4 months compared to 202.4 months for HCMV-IE negative tumors. A higher number of HCMV-LA positive cells in the tumors was also associated with a shorter OS in patients (146.2 months vs. 151.5 months). Conclusions: Our findings suggest a link between HCMV-infections and breast cancer prognosis, which paves the way for potential novel clinical intervention and targeted therapy that may prolong the overall survival of selected patients with breast cancer. Full article

Human cytomegalovirus (HCMV) is a herpesvirus that infects between 40% and 95% of the population worldwide, usually without symptoms. The host immune response keeps the virus in a latent stage, although HCMV can reactivate in an inflammatory context, which could result in sequential lytic/latent viral cycles during the lifetime and thereby participate in HCMV genomic diversity in humans. The high level of HCMV intra-host genomic variability could participate in the oncomodulatory role of HCMV where the virus will favor the development and spread of cancerous cells. Recently, an oncogenic role of HCMV has been highlighted in which the virus will directly transform primary cells; such HCMV strains are named high-risk (HR) HCMV strains. In light of these new findings, this review defines the criteria that characterize HR-HCMV strains and their molecular as well as the phenotypic impact on the infected cell and its tumor microenvironment. Full article

Glioblastoma is the most common and aggressive malignancy in the adult central nervous system. Cytomegalovirus (CMV) plays a crucial role in the pathogenesis and treatment of glioblastoma. We reviewed the epidemiology of CMV in gliomas, the mechanism of CMV-related carcinogenesis, and its therapeutic strategies, offering further clinical practice insights. To date, the CMV infection rate in glioblastoma is controversial, while mounting studies have suggested a high infection rate. The carcinogenesis mechanism of CMV has been investigated in relation to various aspects, including oncomodulation, oncogenic features, tumor microenvironment regulation, epithelial–mesenchymal transition, and overall immune system regulation. In clinical practice, the incidence of CMV-associated encephalopathy is high, and CMV-targeting treatment bears both anti-CMV and anti-tumor effects. As the major anti-CMV treatment, valganciclovir has demonstrated a promising survival benefit in both newly diagnosed and recurrent glioblastoma as an adjuvant therapy, regardless of surgery and the MGMT promoter methylation state. Immunotherapy, including DC vaccines and adoptive CMV-specific T cells, is also under investigation, and preliminary results have been promising. There are still questions regarding the significance of CMV infection and the carcinogenic mechanism of CMV. Meanwhile, studies have demonstrated the clinical benefits of anti-CMV therapy in glioblastoma. Therefore, anti-CMV therapies are worthy of further recognition and investigation. Full article

Background: Human cytomegalovirus (HCMV) oncomodulation, molecular mechanisms, and ability to support polyploid giant cancer cells (PGCCs) generation might underscore its contribution to oncogenesis, especially breast cancers. The heterogeneity of strains can be linked to distinct properties influencing the virus-transforming potential, cancer types induced, and patient’s clinical outcomes. Methods: We evaluated the transforming potential in vitro and assessed the acquired cellular phenotype, genetic and molecular features, and stimulation of stemness of HCMV strains, B544 and B693, isolated from EZH2^HighMyc^High triple-negative breast cancer (TNBC) biopsies. Therapeutic response assessment after paclitaxel (PTX) and ganciclovir (GCV) treatment was conducted in addition to the molecular characterization of the tumor microenvironment (TME). Findings: HCMV-B544 and B693 transformed human mammary epithelial cells (HMECs). We detected multinucleated and lipid droplet-filled PGCCs harboring HCMV. Colony formation was detected and Myc was overexpressed in CMV-Transformed-HMECs (CTH cells). CTH-B544 and B693 stimulated stemness and established an epithelial/mesenchymal hybrid state. HCMV-IE1 was detected in CTH long-term cultures indicating a sustained viral replication. Biopsy B693 unveiled a tumor signature predicting a poor prognosis. CTH-B544 cells were shown to be more sensitive to PTX/GCV therapy. Conclusion: The oncogenic and stemness signatures of HCMV strains accentuate the oncogenic potential of HCMV in breast cancer progression thereby leading the way for targeted therapies and innovative clinical interventions that will improve the overall survival of breast cancer patients. Full article

Human cytomegalovirus (HCMV) is a herpesvirus that alternates lytic and latent infection, infecting between 40 and 95% of the population worldwide, usually without symptoms. During its lytic cycle, HCMV can result in fever, asthenia, and, in some cases, can lead to severe symptoms such as hepatitis, pneumonitis, meningitis, retinitis, and severe cytomegalovirus disease, especially in immunocompromised individuals. Usually, the host immune response keeps the virus in a latent stage, although HCMV can reactivate in an inflammatory context, which could result in sequential lytic/latent viral cycles during the lifetime and thereby participate in the HCMV genomic diversity in humans and the high level of HCMV intrahost genomic variability. The oncomodulatory role of HCMV has been reported, where the virus will favor the development and spread of cancerous cells. Recently, an oncogenic role of HCMV has been highlighted in which the virus will directly transform primary cells and might therefore be defined as the eighth human oncovirus. In light of these new findings, it is critical to understand the role of the immune landscape, including the tumor microenvironment present in HCMV-harboring tumors. Finally, the oncomodulatory/oncogenic potential of HCMV could lead to the development of novel adapted therapeutic approaches against HCMV, especially since immunotherapy has revolutionized cancer therapeutic strategies and new therapeutic approaches are actively needed, particularly to fight tumors of poor prognosis. Full article

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases. Full article

Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent, but generally asymptomatic, infection in most people in the world. However, CMV drives and sustains extremely large numbers of antigen-specific T cells and is, therefore, emerging as an exciting platform for vaccines against infectious diseases and cancer. Indeed, pre-clinical data strongly suggest that CMV-based vaccines can sustain protective CD8⁺ T cell and antibody responses. In the context of vaccines for infectious diseases, substantial pre-clinical studies have elucidated the efficacy and protective mechanisms of CMV-based vaccines, including in non-human primate models of various infections. In the context of cancer vaccines, however, much less is known and only very early studies in mice have been conducted. To develop CMV-based cancer vaccines further, it will be critical to better understand the complex interaction of CMV and cancer. An array of evidence suggests that naturally-acquired human (H)CMV can be detected in cancers, and it has been proposed that HCMV may promote tumor growth. This would obviously be a concern for any therapeutic cancer vaccines. In experimental models, CMV has been shown to play both positive and negative roles in tumor progression, depending on the model studied. However, the mechanisms are still largely unknown. Thus, more studies assessing the interaction of CMV with the tumor microenvironment are needed. This review will summarize the existing literature and major open questions about CMV-based vaccines for cancer, and discuss our hypothesis that the balance between pro-tumor and anti-tumor effects driven by CMV depends on the location and the activity of the virus in the lesion. Full article

Besides its well-described impact in immunosuppressed patients, the role of human cytomegalovirus (HCMV) in the pathogenesis of cancer has been more recently investigated. In cancer, HCMV could favor the progression and the spread of the tumor, a paradigm named oncomodulation. Although oncomodulation could account for part of the protumoral effect of HCMV, it might not explain the whole impact of HCMV infection on the tumor and the tumoral microenvironment. On the contrary cases have been reported where HCMV infection slows down the progression and the spread of the tumor. In addition, HCMV proteins have oncogenic properties per se, HCMV activates pro-oncogenic pathways in infected cells, and recently the direct transformation of cells following HCMV infection has been described, which gave rise to tumors when injected in mice. Thus, beyond the oncomodulation model, this review will assess the direct transforming role of HMCV-infected cells and the potential classification of HCMV as an oncovirus. Full article

Epstein-Barr virus (EBV) is characterized by a bipartite life cycle in which latent and lytic stages are alternated. Latency is compatible with long-lasting persistency within the infected host, while lytic expression, preferentially found in oropharyngeal epithelial tissue, is thought to favor host-to-host viral dissemination. The clinical importance of EBV relates to its association with cancer, which we think is mainly a consequence of the latency/persistency mechanisms. However, studies in murine models of tumorigenesis/lymphomagenesis indicate that the lytic cycle also contributes to cancer formation. Indeed, EBV lytic expression is often observed in established cell lines and tumor biopsies. Within the lytic cycle EBV expresses a handful of immunomodulatory (BCRF1, BARF1, BNLF2A, BGLF5 & BILF1) and anti-apoptotic (BHRF1 & BALF1) proteins. In this review, we discuss the evidence supporting an abortive lytic cycle in which these lytic genes are expressed, and how the immunomodulatory mechanisms of EBV and related herpesviruses Kaposi Sarcoma herpesvirus (KSHV) and human cytomegalovirus (HCMV) result in paracrine signals that feed tumor cells. An abortive lytic cycle would reconcile the need of lytic expression for viral tumorigenesis without relaying in a complete cycle that would induce cell lysis to release the newly formed infective viral particles. Full article