Most research providing evidence for the role of oncogenic viruses in head and neck squamous cell carcinoma (SCC) development is focused on one type of virus without analyzing possible interactions between two or more types of viruses. The aim of this study was to analyse the prevalence of co-infection with human papillomavirus (HPV), Epstein–Barr virus (EBV) and polyoma BK virus (BKPyV) in oral, oropharyngeal and laryngeal squamous cell carcinomas in Polish patients. The correlations between viral infection, SCC, demographic parameters, evidence of metastases and grading were also investigated. Fresh-frozen tumour tissue samples were collected from 146 patients with laryngeal, oropharyngeal and oral cancer. After DNA extraction, the DNA of the studied viruses was detected using polymerase chain rection (PCR) assay. Males (87.7%) with a history of smoking (70.6%) and alcohol abuse (59.6%) prevailed in the studied group. Histological type G2 was recognized in 64.4% cases. The patients were most frequently diagnosed with T2 stage (36.3%) and with N1 stage (45.8%). Infection with at least two viruses was detected in 56.2% of patients. In this group, co-infection with HPV/EBV was identified in 34.1% of cases, EBV/BKV in 23.2%, HPV/BKV in 22.0%, and HPV/EBV/BKV in 20.7%. No difference of multiple infection in different locations of cancer was observed. The prevalence of poorly differentiated tumours (G3) was more frequent in co-infection with all three viruses than EBV or BKV alone. A significant correlation was observed between tumour dimensions (T) and lymph-node involvement (N) in co-infected patients compared to single infection. Further studies are necessary to clarify whether co-infection plays an important role in the initiation and/or progression of oncogenic transformation of oral, oropharyngeal and laryngeal epithelial cells.
Oxidative stress is suggested to be the crucial factor in diabetes mellitus type 2 (DM2) pathogenesis and in the development of diabetic complications. Patients with DM2 may be more susceptible to infections due to hyperglycaemia-induced virulence of various microorganisms. Several studies pointed that Epstein-Barr virus (EBV) infection is associated with reactive oxygen species (ROS) production and/or activation of signalling pathways connected with ROS. The present study analyzed serum activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in DM2 patients with and without EBV infection. Blood and saliva were collected from 120 patients with DM2. EBV DNA was detected in the saliva using nested-PCR technique. Spectrophotometric methods were implemented to determine serum GPx and SOD activity with the use of diagnostic kits produced by Randox Laboratories. GPx and SOD activity was decreased in diabetic patients, with the lowest values in DM2 EBV-positive patients. There was correlation between GPx and SOD activity-with increased value of GPx, SOD activity was also rised. In patients with DM2 history longer than 10 years as well as in DM2 patients with obesity, antioxidant enzymes activity was decreased. Determination of examined parameters may be useful in diabetic patients with EBV infection and could be important prognostic factor.
A microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi living in different niches of the human body, which plays an essential role in many metabolic functions. Modifications in the microbiota composition can lead to several diseases, including metabolic disorders. The aim of this study was to analyze the prevalence of four viruses which can cause persistent infections–Epstein-Barr virus (EBV), human papillomavirus (HPV), cytomegalovirus (CMV), and herpes simplex virus type 1 (HSV-1) in patients with diabetes mellitus type 2 (DM2). Blood, saliva and oral swabs were collected from all the study participants. The nested-PCR technique was used to detect the viral DNA. DNA of at least one virus was detected in 71.1% of diabetic patients and in 30% of individuals without diabetes. In patients with diabetes EBV DNA was detected the most frequently (25.4%), followed by HPV– 19.1%, HSV– 10.4% and CMV– 5.2%. A higher percentage of EBV+HPV co-infection was found among men (30.8%). EBV DNA was statistically more often detected in patients living in rural areas (53.7%), while HPV (91.5%) and EBV+HPV co-infection (22.2%) prevailed among patients from urban areas. In patients with a DM2 history longer than 10 years viral infection was detected more frequently. The prevalence of EBV, HPV and the EBV+HPV co-infection was significantly higher in diabetic patients than in individuals without diabetes. The frequency of these infections depended on the duration of the disease (DM2).
A growing number of studies reveal that oxidative stress is associated with viral infections or cancer development. However, there are few reports assessing the relationships between oxidative stress, viral infection, and carcinogenesis. The present study analyzed the level of total antioxidant status (TAS) as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in patients with oropharyngeal cancer both Epstein-Barr virus (EBV)-positive and EBV-negative in comparison with the control group. The correlations between these parameters and EBV type (wild-type LMP1 (wt-LMP1) or LMP1 with deletion (del-LMP1)), level of antibodies against EBV, the degree of tumor differentiation, and TNM classification were also investigated. Fresh frozen tumor tissue samples collected from 66 patients with oropharyngeal squamous cell carcinoma were tested using nested PCR assay for EBV DNA detection. Spectrophotometric methods were used to measure TAS values as well as SOD and GPx activities in homogenates of tissue, using diagnostic kits produced by Randox Laboratories. Sera from all individuals were investigated using ELISA method to detect the presence of Epstein-Barr virus capsid antigen (EBVCA) IgM and IgG, Epstein-Barr virus nuclear antigen (EBNA) IgG, and early antigen (EA) IgG antibodies. The level of TAS and activities of antioxidant enzymes (GPx and SOD) were significantly decreased in tissues with oropharyngeal cancer, particularly in EBV-positive cases. In 82.3% of patients, wt-LMP1 was detected. Significantly lower TAS, GPx, and SOD values were stated in patients infected with wild-type EBV. The presence of antibodies against early antigen (anti-EA) was detected in over 80% of patients, which suggests reactivation of EBV infection. The correlation between the degree of tumor differentiation and TN classification, especially in EBV-positive patients, was also observed. Determination of these parameters may be useful in evaluating tumor burden in patients with various stages of oropharyngeal cancer and could be an important prognostic factor. Future studies are needed to understand the role of EBV lytic reactivation induced by oxidative stress.
The Epstein-Barr virus (EBV) was discovered in 1964 by Michael Anthony Epstein and Yvonne Barr, who discovered a herpesvirus-like infectious agent in a biopsy specimen from a patient with Burkitt's lymphoma. This virus belongs to the Herpesviridae family (subfamily Gammaherpesvirinae, genus Lymphocryptovirus). EBV is a ubiquitous herpesvirus that is causally associated with various malignant tumours. According to the current nomenclature, it was named human herpesvirus type 4 (human herpesvirus 4 -HHV-4). Primary infection usually occurs in childhood. In developing countries, the infection rate among young children is higher than in developed countries. It was the first human tumour virus and it is currently categorized as a group-1 carcinogen due to its association with various cancers. It is estimated that over 90% of the adult population has been infected with this pathogen, but only a minority will develop the disease. EBV establishes latent infection characterized by the expression of a limited number of viral genes called latent genes. Moreover, during its life cycle, EBV periodically reactivates and can be transmitted to other susceptible hosts. The oral cavity is the main site of EBV occurrence and the most common source of infection. This study discusses EBV frequency and its association with the occurrence of malignant tumours and the pathways of tumour progression.
Introduction. The role of oxidative stress in the pathogenesis of neoplastic diseases, including its connection with viral infections, is the subject of many publications. The results of numerous researches have revealed that virus-induced phagocyte activation is associated with oxidative stress, not only because reactive oxygen species (ROS) are released, but also because activated phagocytes can release cytokines, such as tumour necrosis factor (TNF-alpha) or interleukin-1 (IL-1). Objective. The purpose of this review is to analyze the role of ROS in the pathogenesis of head and neck cancer and correlation between ROS and viruses, especially Epstein-Barr virus (EBV) and Human papillomavirus (HPV), in malignant tumour development in this area. State of knowledge. The effects of an increased amount of ROS or reactive nitrate species (RNS) with a simultaneous reduction of antioxidants are noticed in various cancers, including head and neck cancer. Increased oxidative stress is also associated with disorders in the antioxidant defence system. HPV and EBV, which are important risk factors for head and neck cancer, can act via ROS-based mechanisms. Long-term expression of the Epstein-Barr nuclear antigen 1 (EBNA1) causes increased ROS and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase level. During expression of HPV16infected cells, RNS increase E6 and E7 levels, thereby increasing the level of DNA damage in the cell. ROS are also involved in many benign oral disorders. Conclusion. Reactive oxygen species are involved in various pathological processes in the environment of chronic oxidative stress, including carcinogenicity. ROS contribute to the development of head and neck cancer through many risk factors, such as connection with viruses.
TP 53 promoter methylation was examined in frozen tumor tissue taken from patients with oropharyngeal carcinoma with EBV, HPV and co-infection EBV/HPV. This pilot study was performed on 48 patients. Initial studies indicate a high frequency of methylation in HPV-associated (57.1%) and EBV - associated OSCC (60%) cases, whilst the highest exists in co-infection HPV/EBV (75%). Future studies on a larger group of patients, of the mechanisms of co-infection and their role in oral squamous cell carcinoma, are necessary.
Polyomavirus (PyV) was discovered by accident in 1950 in the course of describing an infectious factor causing multiple tumours in rodents. The term is derived from two Greek words: poly (many) and oma (tumour). At present the family of human polyomaviruses (HPyV) consists of 10 members. One of the first members was BK virus, isolated in 1971 from the urine of a renal transplant patient. Serological examinations have shown that due to its ability to cause latent infection, about 90% of the general population can have specific antibodies attesting infection. In the case of infected persons with normal immunity, this virus is not dangerous. In the impaired immunity, however, loss of immunity results in virus reactivation and development of many life-threatening illnesses. Serological examinations have also reveal that BK polyomavirus considerably affects the development of cancers in humans. Hence, in 2012 a group of 26 researchers from 11 countries associated with the International Agency for Research on Cancer (a part of the World Health Organisation) classified BK polyomavirus within group 2B - “potentially carcinogenic to humans”
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