Tomas Rokos

Background/Objectives: Cervical cancer is a common malignancy in women worldwide, closely associated with persistent human papillomavirus (HPV) infection. Epigenetic mechanisms, particularly promoter methylation, may contribute to tumour progression. This pilot study aimed to analyse the promoter methylation patterns and gene expression of selected genes (DNMT, BCL2, CDH1, CD8A, MUC1, ALCAM). The goal was to identify associations between promoter hypermethylation, gene expression, and HPV infection in cervical swab specimens obtained from patients with low-grade squamous intraepithelial lesions (SILs), high-grade SILs, or squamous cell carcinomas. Methods: A total of 81 cervical swab samples from Slovak participants were included in the study. DNA methylation and gene expression profiling was performed using real-time PCR (qPCR) and pyrosequencing. Results: BCL2 expression was significantly reduced across all lesion grades. CD8A expression was slightly elevated in low- and high-grade SILs, particularly in HPV-positive samples. MUC1 showed variability with lesion grade. No statistically significant differences in DNA methylation were observed across groups stratified by HPV status, community state type, and lesion grade. Conclusions: Our findings suggest that BCL2 downregulation and gene activity variability influenced by the vaginal microbiome may play a role in cervical lesion progression. These results highlight potential non-invasive biomarkers for monitoring cervical lesions.

Background: Cervical cancer remains the fourth most common malignancy among women worldwide. Despite vaccination and regular screening, new molecular biomarkers are needed for improved early detection and risk assessment. MicroRNAs (miRNAs) play crucial roles in post-transcriptional regulation, and their dysregulation may contribute to cervical carcinogenesis. This study evaluated the expression of selected miRNAs in cervical swab samples and corresponding biopsies from women with various grades of cervical lesions and assessed their relationship with human papillomavirus (HPV) infection. Methods: A total of 72 cervical swab samples were included in this study, divided according to cytological severity: negative for intraepithelial lesion or malignancy (NILM, n = 15), atypical squamous cells of undetermined significance (ASC-US, n = 12), low-grade squamous intraepithelial lesion (LSIL, n = 19), and high-grade squamous intraepithelial lesion (HSIL, n = 26). In a subset of patients, corresponding biopsy specimens were analysed for comparison. The association of miRNA expression with HPV infection status was also examined. miRNA expression was quantified by real-time PCR using commercially available assays. Results: To assess the relationship between miRNA expression, lesion severity, and HPV infection, fold change values were compared to the control group (NILM). No significant differences were observed in the ASC-US group (p > 0.05). In contrast, several miRNAs were significantly upregulated in the LSIL and/or HSIL groups, as well as in HPV-positive samples, indicating their association with both lesion progression and viral infection. Specifically, miR-17-5p, miR-26b-5p, miR-29a-3p, miR-103a-3p, miR-106a-5p, miR-146a-5p, miR-155-5p, and miR-191-5p showed increased expression (p < 0.05) compared with controls. The observed upregulation of miR-26b-5p, miR-106a-5p, and miR-146a-5p highlights their potential role in HPV-associated cervical carcinogenesis. Dysregulated miRNAs were enriched in pathways related to infectious diseases, various types of cancer, and cell adhesion processes. Conclusions: The gradual increase in specific miRNAs with lesion severity and HPV infection suggests their role in cervical carcinogenesis. The identified miRNAs may serve as promising non-invasive biomarkers for early detection and monitoring of HPV-associated cervical lesions.

Medicinal mushrooms have been used as a medicinal tool for many centuries and, nowadays, are used in the prevention and therapy of various diseases, including as an adjunct to cancer treatment. It is estimated that 14–16% of global cancer cases are caused by infectious events; one well-known infectious agent that leads to cancer is the human papillomavirus (HPV). HPV is responsible for more than 99.7% of cervical cancer cases and also may play a role in vaginal, vulvar, penile, anal, rectal, and oropharyngeal carcinogenesis. Coriolus versicolor, a basidiomycetes class mushroom, consists of glycoproteins called polysaccharide-K (PSK) and polysaccharopeptide (PSP), which are mainly responsible for its effectiveness in the fight against a variety of cancers. Its beneficial effect lies in its ability to arrest different phases of the cell cycle, immunomodulation or induction of apoptosis. Coriolus versicolor extractcan reduces BCL-2 expression or increases the expression of p53 tumour suppressor genes in breast tumour cell lines. Inhibition of proliferation was also demonstrated with HeLa cells, while cervical cytology abnormalities improved in patients who locally applied Coriolus versicolor-based vaginal gel. Coriolus versicolor extract itself, and also its combination with another medicinal mushroom, Ganoderma lucidum, leads to improved HPV clearance in HPV cervical or oral-positive patients. Medicinal mushrooms can also increase the effectiveness of vaccination. This review considers the use of medicinal mushrooms as a suitable adjunct to the treatment of many cancers or precanceroses, including those caused by the HPV virus.

Some estimates place the proportion of human malignancies attributable to viruses at between 15 and 20 percent. Viruses including the human papillomavirus are considered an interesting but controversial etiological risk factor for breast cancer. HPV infection is anticipated to be an early trigger in breast cancer carcinogenesis, followed by cumulative alterations over time (“hit and run” mechanism) through synergy with other environmental factors. The association between HPV and breast cancer has not yet been verified. There are very conflicting data on the presence of HPV DNA in breast cancer samples, and we lack a clarified, exact mode of HPV transmission to the breast. In our review article we analyzed the up-to-date knowledge about the association of HPV and breast cancer. Furthermore, we summarized the available original research published since 2010. In conclusion, the complexity and inconsistency of the available results together with the relatively low prevalence of HPV infection requires extensive research with much larger studies and exact and unified diagnostic methods are required to better understand the role of the HPV in breast carcinogenesis.

Background: Cervical cancer is the fourth most common malignancy and fourth leading cause of cancer death in women worldwide. More than 99.7% of cases are caused by human papillomavirus (HPV), while HPV types 16 and 18 cause over 70% of all cervical cancer cases. In this preliminary study, we aimed to investigate the presence of HPV infection and diversity of bacteria associated with bacterial vaginosis. Methods: Cervical swabs (n = 21) taken from women aged 21–47 years, in seventeen cases, with different degrees of cervical abnormality, and from four healthy women, were tested for the presence of HPV DNA, as well as the bacterial strains associated with bacterial vaginosis, using the real-time PCR method. Results: HPV16 was the dominant genotype in 53% (9/17) of patients with confirmed precancerous lesions (ASCUS, LSIL, and HSIL). In specimens with confirmed cytological abnormalities and hrHPV infection, we detected a wide diversity of microbes, while the most common species were Gardnerella vaginalis, Atopobium vaginae, Prevotella bivia, Ureaplasma parvum, Ureaplasma urealyticum, Leptotrichia amnionii, Bacteroides ureolyticus, and Sneathia sanguinegens. The presence of pathogens did not differ, depending on the degree of precancerous lesions or HPV type. Conclusion: In our work, HPV16 dominated in patients with cervical precancerous lesions. We also suggest an increased bacterial diversity of the vaginal microbiome in patients with cervical lesions, for which the HPV virus is largely responsible.

Breast cancer, which is the most common malignancy in women, does not form a uniform nosological unit but represents a group of malignant diseases with specific clinical, histopathological, and molecular characteristics. The increasing knowledge of the complex pathophysiological web of processes connected with breast cancercarcinogenesis allows the development of predictive and prognostic gene expressionand molecular classification systems with improved risk assessment, which could be used for individualized treatment. In our review article, we present the up-to-date knowledge about the role of miRNAs and their prognostic and predictive value in luminal A breast cancer. Indeed, an altered expression profile of miRNAs can distinguish not only between cancer and healthy samples, but they can classify specific molecular subtypes of breast cancer including HER2, Luminal A, Luminal B, and TNBC. Early identification and classification of breast cancer subtypes using miRNA expression profilescharacterize a promising approach in the field of personalized medicine. A detection of sensitive and specific biomarkers to distinguish between healthy and early breast cancer patients can be achieved by an evaluation of the different expression of several miRNAs. Consequently, miRNAs represent a potential as good diagnostic, prognostic, predictive, and therapeutic biomarkers for patients with luminal A in the early stage of BC.