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The role of infection of HPV and EBV in the etiology of nasopharyngeal and cervical carcinoma
Machů, Jakub ; Vojtěchová, Zuzana (advisor) ; Španielová, Hana (referee)
Human papillomaviruses (HPV) and Epstein-Barr viruses (EBV) are common DNA viruses that contribute to the development and progression of tumours. These two groups of viruses are associated with more than 600,000 cases of newly diagnosed tumours of different anatomical locations annually. However, carcinogenesis is not a part of their normal productive life cycle. High risk HPV infections are mainly associated with head and neck tumours and anogenital cancers. EBV infections are associated with a range of acute or chronic diseases and tumours, with Burkitt's lymfomas (BL), Hodgkin's lymphomas (HL) and nasopharyngeal carcinomas (NPC) being the most prominent. In recent years, it has been hypothesized that EBV infections may be involved in the development of cervical cancer in woman and that HPV infections may play a role in the development of NPC. The aim of this thesis is to characterize above mentioned groups of DNA viruses and to summarize currently available information about the potential role of these viruses in nasopharyngeal and cervical carcinomas. Key words: human papillomavirus, Epstein-Barr virus, nasopharyngeal carcinoma, cervical carcinoma
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The study of tumour DNA virus integrations
Frčková, Tereza ; Saláková, Martina (advisor) ; Šroller, Vojtěch (referee)
Most people perceive viruses primarily as a cause of diseases such as cold, flu or COVID-19. But there are also viruses with oncogenic potential. There are several ways in which viruses contribute to the development of tumors. In the case of human papillomavirus and Merkel cell virus, it is the expression of oncogenes encoded in viral genomes. The virus may be integrated into the host genome, which can also promote the development of carcinogenesis. In this work, the method of detection of integrated papillomavirus sequence by polymerase chain reaction (DIPS PCR) was used to detect the integration breakpoints in human papillomavirus (HPV) in positive cell lines originated from cervical cancer, clinical head and neck cancer samples associated with HPV, and clinical samples of Merkel cell carcinoma. In the case of Merkel cell carcinoma, DIPS PCR method was performed on samples isolated from fresh frozen tissues and from formalin fixed paraffin embedded (FFPE) sections of tumor samples. In the case of tonsillar tumors associated with HPV, only fresh frozen tissues were used. Integration breakpoints were detected in samples from both fresh frozen and FFPE tissues using DIPS PCR method. For the detection of HPV genome integration breakpoints, a new set of primers was tested and optimized on the SiHa...
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The study of tumour DNA virus intergrations
Frčková, Tereza ; Saláková, Martina (advisor) ; Šroller, Vojtěch (referee)
Most people perceive viruses primarily as the cause of diseases such as cold, flu or COVID-19. But there are also viruses with oncogenic potencial. There are several ways in which viruses provide to the development of tumors. In the case of human papillomavirus and Merkel cell virus, this is the expression of oncogens encoded in viral genomes. The virus may be integrated into the host genome, which can also promote to the development of carcinogenesis. In this work, the method of detection of integrated papillomavirus sequence by polymerase chain reaction (DIPS PCR) was used to detect the integration breakpoints in human papillomavirus (HPV) of positive cell lines originated from cervix cancer, clinical head and neck cancer samples associated with HPV, and clinical samples of cancer from Merkel cells. In the case of Merkel cell carcinoma, the DIPS PCR method was performed on samples isolated from freshly frozen tissue and from cuts of tumor samples stored in paraffin. In the case of tonsil tumors associated with HPV, it was only freshly frozen tissue. Using the DIPS PCR method, integration breakpoints were detected in samples from both freshly frozen tissue and tissue stored in paraffin. For the detection of HPV genome integration breakpoints, a new set of primers was tested, which was optimized on...
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The awareness of health professionals in the field of gynecology about prevention of cervical cancer
Havlíková, Tereza ; Sláma, Jiří (advisor) ; Šimonová, Daniela (referee)
The bachelor thesis deals with the topic of the awareness of health professionals in the field of gynecology about the prevention of cervical carcinoma. The thesis summarizes basic information about primary and secondary prevention, risk factors and clinical symptoms of cervical carcinoma. It also includes information on the diagnosis and subsequent treatment of patients with cervical carcinoma. The main aim of the study was to identify which group of health professionals would have the greatest knowledge of cervical cancer prevention. A total of four research hypotheses were established, of which three were confirmed and only one was disproved. A quantitative type of research was chosen to address them. Data collection was carried out by means of a questionnaire survey conducted at the Obstetrics and Gynecology of the First Faculty of Medicine and General Teaching Hospital in Prague. A questionnaire of twenty-six questions was distributed in paper form among local doctors, midwives and nurses. The final size of the research sample was one hundred respondents. All questions were answered completely voluntarily and anonymously. Tables and graphs summarizing the results of the survey were produced as part of the data analysis. The main finding was that the group of doctors was much more aware of the...
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Immunological aspects of head and neck cancer in relation to etiology
Koucký, Vladimír ; Bouček, Jan (advisor) ; Říhová, Blanka (referee) ; Smilek, Pavel (referee)
Tumor immunology is a progressively developing, multidisciplinary branch of biology. Results of basic research have already been successfully translated to clinical practice. The immediate success of new immunotherapeutic drugs, especially immune checkpoint inhibitors, has further supported the expansion of basic and clinical research in this field. In the case of head and neck squamous cell carcinoma (HNSCC), some immune system elements, such as CD8+ T cells, were shown to play an important role in the progression of the disease. Importantly, HNSCC is a diverse group of diseases, and a significant number of the tumors are induced by high-risk strains of human papillomavirus (HPV). HPV-associated tumors (HPV+ ) respond better to standard therapy, and the immune system was shown to be one of the crucial factors in this phenomenon. We focused on the analysis of phenotype, function, and prognostic value in tumor-infiltrating immune cells in HNSCC patients regarding the HPV status of the tumor. We were able to detect CD8+ tumor-infiltrating T cells reacting to HPV16 antigens in the majority of HPV+ oropharyngeal cancers. Moreover, activity of these T cells was enhanced after blockade of both PD-1 and TIM-3 immune-checkpoint pathways, supporting a concept of combined immunotherapy. In our...
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Functional analysis of differentially expressed miRNAs in HPV positive and HPV negative cell lines derived various anatomical localization
Krbušek, David ; Saláková, Martina (advisor) ; Dostálová Merkerová, Michaela (referee)
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. MiRNA expression profiles showed several differentially expressed miRNAs specific to human papillomavirus (HPV)-associated tumors. These miRNAs include miR-139-5p, which has reduced expression in these tumors. In this thesis, the role of miR-139-5p was studied in vitro on cell lines that were HPV positive (CRL-3240, SiHa) and HPV negative (FaDu, C-33A). Cell lines were transfected with mimic miRNA, the ability of cells to proliferate and migrate was then studied. Cell proliferation was studied using MTT assay, while Scratch wound healing assay and transwell assay were used to evaluate the migratory abilities of the cells. Mediator RNAs (mRNAs) of target genes of miR-139-5p were predicted using TargetScan and miRDB databases. The change in gene expression of target mRNAs, as well as the verification of the successful increase in miRNA expression in the cell lines, was verified using RT-qPCR. Increase of miR-139-5p expression in all used cell lines did not lead to statistically significant changes (p≤0.05) in proliferative or migratory abilities. The mRNAs of FOS, JUN, KIF13A and GDF10 genes were selected as targets of miR-139-5p. Transfected cell lines did not show a noticable reduction in the expression of the target mRNAs....
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Impact of pattern and functional properties of tumor-infiltrating immune cells for clinical outcome of head and neck cancer
Hladíková, Kamila ; Špíšek, Radek (advisor) ; Plzák, Jan (referee) ; Reiniš, Milan (referee)
Head and neck squamous cell carcinoma encompasses a complex and heterogeneous group of malignant diseases. Originally, this tumor type was associated with tobacco and alcohol consumption. However, a significantly expanding subset of tumors associated with oncogenic human papillomavirus infection arising in deep tonsillar crypts was identified within the last decades. Due to the essential role of the immune system in antiviral and anticancer immune response, the prognosis of patients is significantly influenced by the volume, composition and functional capacity of the immune infiltrate. The immunosuppressive landscape of head and neck cancer leads to unfavorable outcome of patients and decreased efficacy of immunotherapy. The response rate to standard treatment is high, however, standard therapy is accompanied by considerable toxicity influencing the quality of life. In 2016, the first immunotherapeutics for the treatment of patients with recurrent squamous cell carcinoma of the head and neck were approved - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab. This type of therapy, based on mitigation of immunosuppression, shows strong efficacy and less toxicity in combination with other therapies. Therefore, anti-PD-1 immunotherapy was recently approved in the first-line...
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Knowledge and attitudes to HPV immunisation IV
Jelínková, Tereza ; Zimčíková, Eva (advisor) ; Kolmanová, Eliška (referee)
Knowledge and attitudes to HPV immunisation IV Author: Tereza Jelínková Thesis supervisor: PharmDr. Eva Zimčíková, Ph.D. Introduction HPV infection is one of the most common sexually transmitted diseases causing, apart from genital warts, other malignancies, most often cervical cancer. The most effective way of prevention is vaccination. So far, there have been 3 types of vaccines, most recent one being the nonavalent vaccine providing up to 90 % protection against cervical cancer- causing HPV, in contrast to the previously available 70 % protection from bivalent or quadrivalent vaccines. Aims The main aim of this thesis was to investigate the knowledge and attitudes towards vaccination against HPV, and knowledge about HPV in general, among secondary school students. Furthermore, to determine their vaccination status and compare the findings with data from previous theses, including a comparison of their knowledge about HPV and relevant prevention. Methodology The data was obtained by means of a questionnaire survey, which took place at three secondary schools. In December 2017 at Gymnázium in Mladá Boleslav, then during June 2018 at Gymnázium in Brandýs nad Labem, and finally in September 2018 at Gymnázium Chotěboř. The obtained data was recorded in a Microsoft Excel spreadsheet and then...
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