Publications by authors named "Ruth Tachezy"

64 Publications

Lack of Conserved miRNA Deregulation in HPV-Induced Squamous Cell Carcinomas.

Biomolecules 2021 05 20;11(5). Epub 2021 May 20.

Department of Genetics and Microbiology, Faculty of Science, Charles University, 12844 Prague, Czech Republic.

Squamous cell carcinomas (SCCs) in the anogenital and head and neck regions are associated with high-risk types of human papillomaviruses (HR-HPV). Deregulation of miRNA expression is an important contributor to carcinogenesis. This study aimed to pinpoint commonly and uniquely deregulated miRNAs in cervical, anal, vulvar, and tonsillar tumors of viral or non-viral etiology, searching for a common set of deregulated miRNAs linked to HPV-induced carcinogenesis. RNA was extracted from tumors and nonmalignant tissues from the same locations. The miRNA expression level was determined by next-generation sequencing. Differential expression of miRNAs was calculated, and the patterns of miRNA deregulation were compared between tumors. The total of deregulated miRNAs varied between tumors of different locations by two orders of magnitude, ranging from 1 to 282. The deregulated miRNA pool was largely tumor-specific. In tumors of the same location, a low proportion of miRNAs were exclusively deregulated and no deregulated miRNA was shared by all four types of HPV-positive tumors. The most significant overlap of deregulated miRNAs was found between tumors which differed in location and HPV status (HPV-positive cervical tumors vs. HPV-negative vulvar tumors). Our results imply that HPV infection does not elicit a conserved miRNA deregulation in SCCs.
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http://dx.doi.org/10.3390/biom11050764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160722PMC
May 2021

ARG1 mRNA Level Is a Promising Prognostic Marker in Head and Neck Squamous Cell Carcinomas.

Diagnostics (Basel) 2021 Mar 31;11(4). Epub 2021 Mar 31.

Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, 252 50 Vestec, Czech Republic.

Head and neck squamous cell carcinomas (HNSCC) can be induced by smoking or alcohol consumption, but a growing part of cases relate to a persistent high-risk papillomavirus (HPV) infection. Viral etiology has a beneficial impact on the prognosis, which may be explained by a specific immune response. Tumor associated macrophages (TAMs) represent the main immune population of the tumor microenvironment with a controversial influence on the prognosis. In this study, the level, phenotype, and spatial distribution of TAMs were evaluated, and the expression of TAM-associated markers was compared in HPV positive (HPV+) and HPV negative (HPV-) tumors. Seventy-three formalin and embedded in paraffin (FFPE) tumor specimens were examined using multispectral immunohistochemistry for the detection of TAM subpopulations in the tumor parenchyma and stroma. Moreover, the mRNA expression of TAM markers was evaluated using RT-qPCR. Results were compared with respect to tumor etiology, and the prognostic significance was evaluated. In HPV- tumors, we observed more pro-tumorigenic M2 in the stroma and a non-macrophage arginase 1 (ARG1)-expressing population in both compartments. Moreover, higher mRNA expression of M2 markers-cluster of differentiation 163 (CD163), ARG1, and prostaglandin-endoperoxide synthase 2 (PTGS2)-was detected in HPV- patients, and of M1 marker nitric oxide synthase 2 (NOS2) in HPV+ group. The expression of ARG1 mRNA was revealed as a negative prognostic factor for overall survival of HNSCC patients.
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http://dx.doi.org/10.3390/diagnostics11040628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065482PMC
March 2021

Aspartate β-hydroxylase as a target for cancer therapy.

J Exp Clin Cancer Res 2020 Aug 18;39(1):163. Epub 2020 Aug 18.

Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, Vestec, Czech Republic.

As metastasis is a major cause of death in cancer patients, new anti-metastatic strategies are needed to improve cancer therapy outcomes. Numerous pathways have been shown to contribute to migration and invasion of malignant tumors. Aspartate β-hydroxylase (ASPH) is a key player in the malignant transformation of solid tumors by enhancing cell proliferation, migration, and invasion. ASPH also promotes tumor growth by stimulation of angiogenesis and immunosuppression. These effects are mainly achieved via the activation of Notch and SRC signaling pathways. ASPH expression is upregulated by growth factors and hypoxia in different human tumors and its inactivation may have broad clinical impact. Therefore, small molecule inhibitors of ASPH enzymatic activity have been developed and their anti-metastatic effect confirmed in preclinical mouse models. ASPH can also be targeted by monoclonal antibodies and has also been used as a tumor-associated antigen to induce both cluster of differentiation (CD) 8 and CD4 T cells in mice. The PAN-301-1 vaccine against ASPH has already been tested in a phase 1 clinical trial in patients with prostate cancer. In summary, ASPH is a promising target for anti-tumor and anti-metastatic therapy based on inactivation of catalytic activity and/or immunotherapy.
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http://dx.doi.org/10.1186/s13046-020-01669-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433162PMC
August 2020

Prevalence and Risk Factors for Oral HPV in Healthy Population, in Central Europe.

Anticancer Res 2020 Mar;40(3):1597-1604

Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, Vestec, Czech Republic

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http://dx.doi.org/10.21873/anticanres.14107DOI Listing
March 2020

Detailed Characteristics of Tonsillar Tumors with Extrachromosomal or Integrated Form of Human Papillomavirus.

Viruses 2019 12 30;12(1). Epub 2019 Dec 30.

Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, Průmyslová 595, 25250 Vestec, Czech Republic.

The human papillomavirus (HPV) integration, the critical step in viral carcinogenesis, most frequently occurs in the E2 gene, which results in its inactivation and in an increase of E6/E7 transcription. However, in a substantial number of tumors, the virus is present in an extrachromosomal form. For those tumors, the transformation mechanisms are not fully elucidated. Here we evaluated the possible mechanism of inactivating the E2 without interruption of the gene, methylation or mutation of the E2 binding sites (E2BSs) in HPV16-positive tonsillar tumors by next-generation and Sanger sequencing. Viral genome status was analyzed by the amplification of papillomavirus oncogene transcripts assay (APOT) and mRNA mapping, and expression of viral oncogenes was performed by qPCR. The methylation of E2BSs was significantly higher in tumors with an integrated, in comparison to extrachromosomal, form of the viral genome. No mutations were detected in the E2BSs. The viral oncogenes were equally expressed in samples with an integrated and extrachromosomal form of the virus. Only the nucleotide variants were identified in the E2 gene. No proposed mechanism of E2 inactivation was confirmed in tonsillar tumors with an extrachromosomal form of the HPV genome. The expression of E6/E7 genes seems to be sufficient to initiate and maintain the carcinogenic process.
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http://dx.doi.org/10.3390/v12010042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019694PMC
December 2019

Prognostic value of posttreatment HPV-specific antibodies in patients with oropharyngeal tumors.

J Surg Oncol 2019 Aug 15;120(2):117-124. Epub 2019 Apr 15.

Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, Průmyslová, Vestec, Czech Republic.

Background: The presence of human papillomavirus (HPV)-specific antibodies in patients with head and neck cancer at enrollment has prognostic significance. In cervical carcinoma patients, the decrease of HPV E6/E7-specific antibodies appears to be associated with a better prognosis.

Methods: This prospective study with follow-up focused on the persistence and prognostic value of antibodies specific for HR HPV-derived VLPs and HPV16 E6/E7 oncoproteins in patients with oropharyngeal cancers. In this study, we analyzed sera of 93 patients taken a year after the end of treatment and sera from 58 of these patients taken up to 14 years after treatment.

Results: The level of HPV-specific antibodies decreased on the 1-year follow-up and the decrease during the long follow-up was statistically significant. For HPV16 E7 antibodies the decrease was steeper in nonrecurrent patients. While the level of antibodies at enrollment was not predictive of recurrences, the decrease of HPV16 E6 antibodies at 1-year follow up was associated with better overall as well as disease-specific survival of patients.

Conclusions: The data suggest that the pretreatment level of HPV-specific antibodies is not predictive of the occurrence of recurrences but the decrease HPV16 E6 antibodies on the 1-year follow-up is predictive of better survival of HN patients.
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http://dx.doi.org/10.1002/jso.25473DOI Listing
August 2019

Implementation of Mass Cytometry for Immunoprofiling of Patients with Solid Tumors.

J Immunol Res 2019 11;2019:6705949. Epub 2019 Feb 11.

Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, Průmyslová 595, 25250 Vestec, Czech Republic.

Monitoring immune responses to solid cancers may be a better prognostic tool than conventional staging criteria, and it can also serve as an important criterion for the selection of individualized therapy. Multiparametric phenotyping by mass cytometry extended possibilities for immunoprofiling. However, careful optimization of each step of such method is necessary for obtaining reliable results. Also, with respect to procedure length and costs, sample preparation, staining, and storage should be optimized. Here, we designed a panel of 31 antibodies which allows for identification of several subpopulations of lymphoid and myeloid cells in a solid tumor and peripheral blood simultaneously. For sample preparation, disaggregation of tumor tissue with two different collagenases combined with DNase I was compared, and removal of dead or tumor cells by magnetic separation was evaluated. Two possible procedures of barcoding for single-tube staining of several samples were examined. While the palladium-based barcoding affected the stability of several antigens, the staining with two differently labeled CD45 antibodies was suitable for cells isolated from a patient's blood and tumor. The storage of samples in the intercalation solution for up to two weeks did not influence results of the analysis, which allowed the measurement of samples collected within this interval on the same day. This procedure optimized on samples from patients with head and neck squamous cell carcinoma enabled identification of various immune cells including rare subpopulations.
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http://dx.doi.org/10.1155/2019/6705949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388349PMC
June 2019

Genome-wide miRNA profiling reinforces the importance of miR-9 in human papillomavirus associated oral and oropharyngeal head and neck cancer.

Sci Rep 2019 02 19;9(1):2306. Epub 2019 Feb 19.

Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.

Head and neck cancer is the sixth most common malignancy worldwide, predominantly developing from squamous cell epithelia (HNSCC). The main HNSCC risk factors are tobacco, excessive alcohol use, and the presence of human papillomavirus (HPV). HPV positive (+) cancers are etiologically different from other HNSCC and often show better prognosis. The current knowledge regarding HNSCC miRNA profiles is still incomplete especially in the context of HPV+ cancer. Thus, we analyzed 61 freshly collected primary oral (OSCC) and oropharyngeal (OPSCC) SCC samples. HPV DNA and RNA was found in 21% cases. The Illumina whole-genome small-RNA profiling by next-generation sequencing was done on 22 samples and revealed 7 specific miRNAs to HPV+ OSCC, 77 to HPV+ OPSCC, and additional 3 shared with both; 51 miRNAs were specific to HPV- OPSCC, 62 to HPV- OSCC, and 31 shared with both. The results for 9 miRNAs (miR-9, -21, -29a, -100, -106b, -143 and -145) were assessed by reverse transcription-quantitative polymerase chain reaction on the whole study population. The data was additionally confirmed by reanalyzing publicly available miRNA sequencing Cancer Genome Atlas consortium (TCGA) HNSCC data. Cell signaling pathway analysis revealed differences between HPV+ and HPV- HNSCC. Our findings compared with literature data revealed extensive heterogeneity of miRNA deregulation with only several miRNAs consistently affected, and miR-9 being the most likely HPV related miRNA.
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http://dx.doi.org/10.1038/s41598-019-38797-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381209PMC
February 2019

Experimental Combined Immunotherapy of Tumours with Major Histocompatibility Complex Class I Downregulation.

Int J Mol Sci 2018 Nov 21;19(11). Epub 2018 Nov 21.

Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, 25250 Vestec, Czech Republic.

Combined immunotherapy constitutes a novel, advanced strategy in cancer treatment. In this study, we investigated immunotherapy in the mouse TC-1/A9 model of human papillomavirus type 16 (HPV16)-associated tumors characterized by major histocompatibility complex class I (MHC-I) downregulation. We found that the induction of a significant anti-tumor response required a combination of DNA vaccination with the administration of an adjuvant, either the synthetic oligodeoxynucleotide ODN1826, carrying immunostimulatory CpG motifs, or α-galactosylceramide (α-GalCer). The most profound anti-tumor effect was achieved when these adjuvants were applied in a mix with a one-week delay relative to DNA immunization. Combined immunotherapy induced tumor infiltration with various subsets of immune cells contributing to tumor regression, of which cluster of differentiation (CD) 8⁺ T cells were the predominant subpopulation. In contrast, the numbers of tumor-associated macrophages (TAMs) were not markedly increased after immunotherapy but in vivo and in vitro results showed that they could be repolarized to an anti-tumor M1 phenotype. A blockade of T cell immunoglobulin and mucin-domain containing-3 (Tim-3) immune checkpoint had a negligible effect on anti-tumor immunity and TAMs repolarization. Our results demonstrate a benefit of combined immunotherapy comprising the activation of both adaptive and innate immunity in the treatment of tumors with reduced MHC-I expression.
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http://dx.doi.org/10.3390/ijms19113693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274939PMC
November 2018

Dysfunction of HPV16-specific CD8+ T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1.

Oral Oncol 2018 07 26;82:75-82. Epub 2018 May 26.

Sotio, Jankovcova 1518/2, 170 00 Prague, Czech Republic. Electronic address:

Background: Human papillomavirus (HPV) type 16 infection is one of the most important etiological agents of oropharyngeal squamous cell carcinoma. Patients with HPV-associated carcinomas of the head and neck were reported to have a better clinical outcome than patients with HPV-negative tumors. Because HPV16 E6 and E7 oncoproteins are highly immunogenic and constitutively expressed, HPV-specific T cell immunity may play the key role in improving the prognosis of these patients.

Methods: Tumor-derived T cells were expanded in high levels of IL-2 and stimulated with HPV16 E6/E7 peptides in the presence or absence of anti-PD-1 monoclonal antibody nivolumab and soluble Tim-3.

Results: HPV16-specific tumor-infiltrating T cells were present in 73.1% of HPV-associated oropharyngeal tumors. HPV16 specific CD8+ TILs were able to produce IFNγ upon specific stimulation and predominantly expressed PD-1 but not Tim-3. Specific IFNγ production was further enhanced after a blockade of both PD-1 and Tim-3 pathways but not after a PD-1 blockade alone. Additionally, the specific stimulation of anti-HPV16 CD8+ T cells suppressed Tim-3 upregulation after the PD-1 blockade.

Conclusion: Our data provide the rationale for combination cancer immunotherapy approaches, including the dual blockade of PD-1 and Tim-3 and, potentially, the use of HPV16-directed therapeutic vaccines.
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http://dx.doi.org/10.1016/j.oraloncology.2018.05.010DOI Listing
July 2018

The Role of miRNAs in Virus-Mediated Oncogenesis.

Int J Mol Sci 2018 Apr 17;19(4). Epub 2018 Apr 17.

Department of Genetics and Microbiology, Faculty of Science, Charles University, Průmyslová 595, Vestec, CZ-25250, 128 44 Prague, Czech Republic.

To date, viruses are reported to be responsible for more than 15% of all tumors worldwide. The oncogenesis could be influenced directly by the activity of viral oncoproteins or by the chronic infection or inflammation. The group of human oncoviruses includes Epstein–Barr virus (EBV), human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), human herpesvirus 8 (HHV-8) or polyomaviruses, and transregulating retroviruses such as HIV or HTLV-1. Most of these viruses express short noncoding RNAs called miRNAs to regulate their own gene expression or to influence host gene expression and thus contribute to the carcinogenic processes. In this review, we will focus on oncogenic viruses and summarize the role of both types of miRNAs, viral as well as host’s, in the oncogenesis.
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http://dx.doi.org/10.3390/ijms19041217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979478PMC
April 2018

Comparison of the miRNA expression profiles in fresh frozen and formalin-fixed paraffin-embedded tonsillar tumors.

PLoS One 2017 23;12(6):e0179645. Epub 2017 Jun 23.

Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czech Republic.

MicroRNAs are considered as promising prognostic and diagnostic biomarkers of human cancer since their profiles differ between tumor types. Most of the tumor profiling studies were performed on rarely available fresh frozen (FF) samples. Alternatively, archived formalin-fixed paraffin-embedded (FFPE) tissue samples are also well applicable to larger-scale retrospective miRNA profiling studies. The aim of this study was to perform systematic comparison of the miRNA expression profiles between FF and macrodissected FFPE tonsillar tumors using the TaqMan Low Density Array system, with the data processed by different software programs and two types of normalization methods. We observed a marked correlation between the miRNA expression profiles of paired FF and FFPE samples; however, only 27-38% of the differentially deregulated miRNAs overlapped between the two source systems. The comparison of the results with regard to the distinct modes of data normalization revealed an overlap in 58-67% of differentially expressed miRNAs, with no influence of the choice of software platform. Our study highlights the fact that for an accurate comparison of the miRNA expression profiles from published studies, it is important to use the same type of clinical material and to test and select the best-performing normalization method for data analysis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179645PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482461PMC
October 2017

Concordance of HPV-DNA in cervical dysplasia or genital warts in women and their monogamous long-term male partners.

J Med Virol 2017 09 12;89(9):1662-1670. Epub 2017 May 12.

Department of Dermatovenereology, Bulovka Hospital, 2nd Medical Faculty Charles University, Prague, Czech Republic.

Transmission of human papillomavirus (HPV) is a premise for development of cervical dysplasia and genital warts (GWs). This cross-sectional study assesses concordance of HPV types present in GWs or cervical dysplasia in women and genital infection of their monogamous male partners in conjunction with seroprevalence of HPV-6, -11, -16, and -18 antibodies. Blood was taken from both women and men, as well a smear of the urogenital area of men. HPV DNA detection in women was done in fixed paraffin embedded tissues under histological control. Of 143 couples who agreed to participate in the study, 68 met inclusion criteria. Type-specific concordance was observed in 32.5% (13/40) of couples in which women had genital warts and in 32.1% (9/28) of couples in which women had cervical dysplasia. In multivariate analysis only smoking in women was associated with concordance (P < 0.05). Prevalence of HPV-specific antibodies was high in male partners, but was not associated with presence of the same HPV type on their genitals. The same type-specific HPV antibodies were detected in 81.8% of men in couples with HPV-6 concordant genital warts, but only in 14.3% of men in couples with HPV-16 concordant cervical dysplasia (P < 0.01). These results suggest that type-specific HPV concordance in genital warts and cervical dysplasia lesions of women and genital infection of their male partners is common and similar. Higher seroconversion in couples with HPV-6 concordant genital warts compared with couples with HPV-16 concordant cervical dysplasia may be explained by viral load exposure.
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http://dx.doi.org/10.1002/jmv.24824DOI Listing
September 2017

The prevalence of HPV infections in HPV-vaccinated women from the general population.

APMIS 2017 Jun 15;125(6):585-595. Epub 2017 Mar 15.

Department of Immunology, Institute of Haematology and Blood Transfusion, Prague, Czech Republic.

Currently, three prophylactic HPV vaccines are commercially available to prevent HPV 16/18 infection and associated lesions. The aim of the study was to assess markers of HPV infection in women/girls before vaccination and to ascertain the prevalence and spectrum of post-vaccination HPV types. Three hundred and thirty subjects of which 75 were virgins were enrolled. Before the first dose of the HPV vaccine and 1, 3 and 5 years after the completion of HPV vaccination, the samples for cytology, HPV detection and anti-HPV antibody response were taken. At enrolment, HPV DNA was detected in 38% of sexually active girls/women. At the first, second and third follow-up, HPV DNA was found in 40, 45, and 39% of them. The seroprevalence rates to HPV 6, 11, 16 and 18 in these subjects were 31, 21, 18 and 10%. On the follow-up significantly higher levels of antibodies to HPV 16/18 were found after application of divalent vaccine. Results of the study demonstrate high prevalence of HPV infection in young women. In a substantial number of women, HPV-specific antibodies as well as high-risk HPV types were detected. HPV-specific antibodies were also frequently found in non-sexually active girls. The acquisition of HPV after the onset of sexual life was very fast.
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http://dx.doi.org/10.1111/apm.12677DOI Listing
June 2017

Prevalence of HPV Infection in Racial-Ethnic Subgroups of Head and Neck Cancer Patients.

Carcinogenesis 2017 02 26;38(2):218-229. Epub 2016 Dec 26.

Department of Otorhinolaryngology-Head and Neck Surgery, GROW Institute, Maastricht University Medical Centre, Maastricht, The Netherlands.

The landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial/ethnic background. The meta-analysis revealed that the prevalence of HPV16 was higher among Blacks with oropharyngeal cancer than Blacks with non-oropharyngeal cancer. However, there was great heterogeneity observed among studies (Q test P<0.0001). In the pooled analysis, after adjusting for each study, year of diagnosis, age, gender and smoking status, the prevalence of HPV16/18 in oropharyngeal cancer patients was highest in Whites (61.1%), followed by 58.0% in Blacks and 25.2% in Asians (P<0.0001). There was no statistically significant difference in HPV16/18 prevalence in non-oropharyngeal cancer by race (P=0.682). With regard to the pattern of HPV16/18 status and p16 expression, White patients had the highest proportion of HPV16/18+/p16+ oropharyngeal cancer (52.3%), while Asians and Blacks had significantly lower proportions (23.0% and 22.6%, respectively) [P <0.0001]. Our findings suggest that the pattern of HPV16/18 status and p16 expression in oropharyngeal cancer appears to differ by race and this may contribute to survival disparities.
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http://dx.doi.org/10.1093/carcin/bgw203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191086PMC
February 2017

Expression of genes encoding centrosomal proteins and the humoral response against these proteins in chronic myeloid leukemia.

Oncol Rep 2017 Jan 7;37(1):547-554. Epub 2016 Nov 7.

Department of Immunology, Institute of Hematology and Blood Transfusion, CZ-128 20 Prague, Czech Republic.

As the extent of centrosome abnormalities in chronic myeloid leukemia (CML) correlates with disease stage and karyotype alterations, abnormal expression of genes encoding centrosomal proteins may be an early prognostic marker of disease progression. In the present study, we showed that in comparison with healthy controls, the expression of four centrosomal genes (AURKA, HMMR, PLK1 and ESPL1) in the peripheral blood of CML patients was significantly enhanced at diagnosis and decreased to the basal level in most patients treated with imatinib mesylate for three months. In the remaining patients (17%), this decrease was delayed and was associated with worse overall survival. The detection of antibodies in sera showed that patients with higher overall antibody production had superior outcomes in terms of achieving major molecular response and failure-free survival. These data suggest that the dynamics of the response of centrosomal genes should be considered as a risk factor and immunity against centrosomal proteins may contribute to treatment response.
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http://dx.doi.org/10.3892/or.2016.5226DOI Listing
January 2017

High prevalence of genital HPV infection among long-term monogamous partners of women with cervical dysplasia or genital warts-Another reason for HPV vaccination of boys.

Dermatol Ther 2017 Jan 9;30(1). Epub 2016 Oct 9.

Dermatovenereology Department, Na Bulovce Hospital, 2nd Medical Faculty Charles University, Prague, Czech Republic.

We conducted a cross-sectional study on the occurrence of a specific type of genital human papillomavirus (HPV) among long-term monogamous male partners of women with cervical dysplasia and genital warts. The purpose of the study was to improve knowledge with regards to the management of these couples. The presence of genital HPV-DNA was detected by PCR with broad spectrum primers followed by hybridization. 82 males met the study criteria, 41 in each group. Genital HPV-DNA prevalence was 67.5% in the genital warts group and 72.2% in the cervical dysplasia group. The prevalence of high risk HPVs was higher in the cervical dysplasia group, while low risk HPVs were more prevalent in the genital warts group (p < .05). The prevalence of HPV in males was independent of the duration of the relationship (73.5% for 6-24 months and 66.7% for longer relationships). In conclusion, our results suggest that the prevalence of the genital HPV infection in both groups of male partners is comparable and very high, but the spectrum of HPV types varies significantly. The presence of the genital HPV infection in male sexual partners seems to be independent of the duration of the relationship. Applying the HPV vaccination to boys may prevent this phenomenon.
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http://dx.doi.org/10.1111/dth.12435DOI Listing
January 2017

Beta-HPV types in patients with head and neck pathology and in healthy subjects.

J Clin Virol 2016 09 28;82:159-165. Epub 2016 Jul 28.

Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Czech Republic. Electronic address:

Background: Human papillomaviruses (HPV) are a heterogeneous group of viruses classified into five genera. The beta-HPV type (beta-PV) infection is very common but mostly asymptomatic in immunocompetent individuals. However, beta-PVs play a role in Epidermodysplasia verruciformis and possibly in non-melanoma skin cancer. Head and neck cancer (HNC) is a common cancer type worldwide and high-risk alpha-PV involvement in HNC has been extensively studied but beta-PV types have rarely been the focus of such studies.

Objectives: To evaluate the prevalence of beta-PV types in HNC, subjects with non-malignant or potentially pre-malignant oral lesions, and healthy controls.

Study Design: The frequency of different beta-PVs in samples from oral (n=35) and oropharyngeal (n=35) cancer patients, gender- and age-matched healthy controls (n=70), and subjects with various non-malignant or potentially pre-malignant oral lesions (n=102) was assessed by a highly sensitive, bead-based, multiplex genotyping assay.

Results: Overall, 54.8% of all tested samples contained at least one beta-PV type. Even though the correlation between types found in lavage and tissue specimens from cancer patients was low, there was a large statistically significant difference between oropharyngeal cancer patients and matched controls for HPV5 (P=0.003; OR=15.58) and between both oral (P=0.026; OR=5.7) and oropharyngeal cancer patients (P=0.002; OR=25.5) and controls for HPV122. In addition, there was no correlation between the prevalence of alpha and beta-PVs in the study patients.

Conclusion: The study provides new data on the prevalence of beta-PVs in HNC. HPV5 was found significantly associated with HNC as already observed by other studies. Additionally, the significant association of HPV122 with HNC might warrant further study as this type has not been extensively studied so far.
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http://dx.doi.org/10.1016/j.jcv.2016.07.019DOI Listing
September 2016

Comparison of the miRNA profiles in HPV-positive and HPV-negative tonsillar tumors and a model system of human keratinocyte clones.

BMC Cancer 2016 07 4;16:382. Epub 2016 Jul 4.

Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.

Background: Better insights into the molecular changes involved in virus-associated and -independent head and neck cancer may advance our knowledge of HNC carcinogenesis and identify critical disease biomarkers. Here we aimed to characterize the expression profiles in a matched set of well-characterized HPV-dependent and HPV-independent tonsillar tumors and equivalent immortalized keratinocyte clones to define potential and clinically relevant biomarkers of HNC of different etiology.

Methods: Fresh frozen tonsillar cancer tissues were analyzed together with non-malignant tonsillar tissues and compared with cervical tumors and normal cervical tissues. Furthermore, relative miRNAs abundance levels of primary and immortalized human keratinocyte clones were evaluated. The global quantitation of miRNA gene abundance was performed using a TaqMan Low Density Array system. The confirmation of differentially expressed miRNAs was performed on a set of formalin-fixed paraffin-embedded tumor samples enriched for the tumor cell fraction by macrodissection.

Results: We defined 46 upregulated and 31 downregulated miRNAs characteristic for the HPV-positive tonsillar tumors and 42 upregulated miRNAs and 42 downregulated miRNAs characteristic for HPV-independent tumors. In comparison with the expression profiles in cervical tumors, we defined miR-141-3p, miR-15b-5p, miR-200a-3p, miR-302c-3p, and miR-9-5p as specific for HPV induced malignancies. MiR-335-5p, miR-579-3p, and miR-126-5p were shared by the expression profiles of HPV-positive tonsillar tumors and of the HPV immortalized keratinocyte clones, whereas miR-328-3p, miR-34c-3p, and miR-885-5p were shared by the miRNA profiles of HPV-negative tonsillar tumors and the HPV-negative keratinocytes.

Conclusions: We identified the miRNAs characteristic for HPV-induced tumors and tonsillar tumors of different etiology, and the results were compared with those of the model system. Our report presents the basis for further investigations leading to the identification of clinically relevant diagnostic and/or therapeutic biomarkers for tumors of viral and non-viral etiology.
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http://dx.doi.org/10.1186/s12885-016-2430-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932682PMC
July 2016

Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences.

J Virol 2016 06 12;90(11):5503-5513. Epub 2016 May 12.

Department of Experimental Virology, National Reference Laboratory for Papillomaviruses, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.

Unlabelled: Human papillomavirus 11 (HPV11) is an etiological agent of anogenital warts and laryngeal papillomas and is included in the 4-valent and 9-valent prophylactic HPV vaccines. We established the largest collection of globally circulating HPV11 isolates to date and examined the genomic diversity of 433 isolates and 78 complete genomes (CGs) from six continents. The genomic variation within the 2,800-bp E5a-E5b-L1-upstream regulatory region was initially studied in 181/207 (87.4%) HPV11 isolates collected for this study. Of these, the CGs of 30 HPV11 variants containing unique single nucleotide polymorphisms (SNPs), indels (insertions or deletions), or amino acid changes were fully sequenced. A maximum likelihood tree based on the global alignment of 78 HPV11 CGs (30 CGs from our study and 48 CGs from GenBank) revealed two HPV11 lineages (lineages A and B) and four sublineages (sublineages A1, A2, A3, and A4). HPV11 (sub)lineage-specific SNPs within the CG were identified, as well as the 208-bp representative region for CG-based phylogenetic clustering within the partial E2 open reading frame and noncoding region 2. Globally, sublineage A2 was the most prevalent, followed by sublineages A1, A3, and A4 and lineage B.

Importance: This collaborative international study defined the global heterogeneity of HPV11 and established the largest collection of globally circulating HPV11 genomic variants to date. Thirty novel complete HPV11 genomes were determined and submitted to the available sequence repositories. Global phylogenetic analysis revealed two HPV11 variant lineages and four sublineages. The HPV11 (sub)lineage-specific SNPs and the representative region identified within the partial genomic region E2/noncoding region 2 (NCR2) will enable the simpler identification and comparison of HPV11 variants worldwide. This study provides an important knowledge base for HPV11 for future studies in HPV epidemiology, evolution, pathogenicity, prevention, and molecular assay development.
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http://dx.doi.org/10.1128/JVI.03149-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4934746PMC
June 2016

Detection of human polyomaviruses MCPyV, HPyV6, and HPyV7 in malignant and non-malignant tonsillar tissues.

J Med Virol 2016 Apr 9;88(4):695-702. Epub 2015 Nov 9.

Department of Immunology, Institute of Hematology and Blood Transfusion, Prague, U Nemocnice 1, Czech Republic.

Merkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma (MCC), a rare skin malignancy. Human polyomavirus six and seven (HPyV6 and HPyV7) were identified on a skin but have not been associated with any pathology. The serology data suggest that infection with polyomaviruses occurs in childhood and they are widespread in population. However, the site of persistent infection has not been identified. Altogether, 103 formalin-fixed paraffin-embedded (FFPE) specimens and five fresh frozen tissues (FF) of non-malignant tonsils and 97 FFPE and 15 FF samples of tonsillar carcinomas were analyzed by qPCR for the presence of MCPyV, HPyV6, and HPyV7 DNA. All MCPyV DNA positive FF tissues were screened for the expression of early viral transcripts. Overall prevalence of MCPyV, HPyV6, and HPyV7 in non-malignant tonsillar tissues was 10.2%, 4.6%, and, 0.9%, respectively. The prevalence of MCPyV DNA in non-malignant tonsils increased with age (P < 0.05). While the prevalence of MCPyV DNA was significantly higher in the tumors than non-malignant tissues (35.7% vs. 10.2%) (P < 0.001), the prevalence of HPyV6 DNA (5.4% vs. 4.6%) and HPyV7 DNA (1.8% vs. 0.9%) were comparable. In all MCPyV DNA positive FF tissues early transcripts were detected. MCPyV, HPyV6, and HPyV7 DNAs were found in tonsils, suggesting that the tonsils may be a site of viral latency. The viral load was low indicating that only a fraction of cells are infected. The higher prevalence of MCPyV DNA was detected in tonsillar tumors but there was no difference in the viral load between tumor and healthy tissues.
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http://dx.doi.org/10.1002/jmv.24385DOI Listing
April 2016

Analysis of the integration of human papillomaviruses in head and neck tumours in relation to patients' prognosis.

Int J Cancer 2016 Jan 13;138(2):386-95. Epub 2015 Aug 13.

Department of Immunology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.

Integration, which leads to the disruption of the circular HPV genome, is considered as a critical, albeit not obligatory, step in carcinogenic progression. Although cervical carcinomas with extrachromosomal HPV plasmid genomes have been described, the virus is integrated in 70% of HPV16-positive cervical tumours. Limited information is available about HPV integration in head and neck tumours (HNC). In this study, we have characterised the physical status of HPV in a set of tonsillar tumour samples using different methods--the mapping of E2 integration breakpoint at the mRNA level, the 3' RACE based Amplification of Papillomavirus Oncogene Transcripts (APOT) assay and Southern blot. Furthermore, the impact of HPV integration on patients' prognosis has been evaluated in a larger set of 186 patients with head and neck cancer. Based on the analysis of E2 mRNA, HPV was integrated in the host genome in 43% of the HPV-positive samples. Extrachromosomal or mixed form was present in 57%. In fresh frozen samples, the APOT and E2 mapping results were in agreement. The results were confirmed using Southern blotting. Furthermore, the type and exact site of integration were determined. The survival analysis of 186 patients revealed HPV positivity, tumour size and lymph node positivity as factors that influence disease specific survival. However, no statistically significant difference was found in disease specific survival between patients with HPV-positive integrated vs. extrachromosomal/mixed forms of the virus.
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http://dx.doi.org/10.1002/ijc.29712DOI Listing
January 2016

High-throughput analysis of human cytomegalovirus genome diversity highlights the widespread occurrence of gene-disrupting mutations and pervasive recombination.

J Virol 2015 08 13;89(15):7673-7695. Epub 2015 May 13.

Laboratory of Clinical Virology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium

Human cytomegalovirus is a widespread pathogen of major medical importance. It causes significant morbidity and mortality in the immunocompromised and congenital infections can result in severe disabilities or stillbirth. Development of a vaccine is prioritized, but no candidate is close to release. Although correlations of viral genetic variability with pathogenicity are suspected, knowledge about strain diversity of the 235kb genome is still limited. In this study, 96 full-length human cytomegalovirus genomes from clinical isolates were characterized, quadrupling the available information for full-genome analysis. These data provide the first high-resolution map of human cytomegalovirus interhost diversity and evolution. We show that cytomegalovirus is significantly more divergent than all other human herpesviruses and highlight hotspots of diversity in the genome. Importantly, 75% of strains are not genetically intact, but contain disruptive mutations in a diverse set of 26 genes, including immunomodulative genes UL40 and UL111A. These mutants are independent from culture passaging artifacts and circulate in natural populations. Pervasive recombination, which is linked to the widespread occurrence of multiple infections, was found throughout the genome. Recombination density was significantly higher than in other human herpesviruses and correlated with strain diversity. While the overall effects of strong purifying selection on virus evolution are apparent, evidence of diversifying selection was found in several genes encoding proteins that interact with the host immune system, including UL18, UL40, UL142 and UL147. These residues may present phylogenetic signatures of past and ongoing virus-host interactions.

Importance: Human cytomegalovirus has the largest genome of all viruses that infect humans. Currently, there is a great interest in establishing associations between genetic variants and strain pathogenicity of this herpesvirus. Since the number of publicly available full-genome sequences is limited, knowledge about strain diversity is highly fragmented and biased towards a small set of loci. Combined with our previous work, we have now contributed 101 complete genome sequences. We have used these data to conduct the first high-resolution analysis of interhost genome diversity, providing an unbiased and comprehensive overview of cytomegalovirus variability. These data are of major value to the development of novel antivirals and a vaccine and to identify potential targets for genotype-phenotype experiments. Furthermore, they have enabled a thorough study of the evolutionary processes that have shaped cytomegalovirus diversity.
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http://dx.doi.org/10.1128/JVI.00578-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505652PMC
August 2015

Distinct patterns of intratumoral immune cell infiltrates in patients with HPV-associated compared to non-virally induced head and neck squamous cell carcinoma.

Oncoimmunology 2015 Jan 30;4(1):e965570. Epub 2015 Jan 30.

Sotio, Prague , Czech Republic ; Department of Immunology; 2nd Faculty of Medicine; Charles University; Motol University Hospital ; Prague, Czech Republic.

Human papillomavirus (HPV) infection is one of the most important etiologic causes of oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients with HPV-positive HNSCC were reported to have a better clinical outcome than patients with HPV-negative cancers. However, little is known about the possible causes of different clinical outcomes. In this study, we analyzed a detailed immune profile of tumor samples from HNSCC patients with respect to their HPV status. We analyzed the characteristics of immune cell infiltrates, including the frequency and distribution of antigen-presenting cells and naïve, regulatory and effector T cells and the cytokine and chemokine levels in tumor tissue. There was a profound difference in the extent and characteristics of intratumoral immune cell infiltrates in HNSCC patients based on their HPV status. In contrast to HPV-negative tumor tissues, HPV-positive tumor samples showed significantly higher numbers of infiltrating IFNγ CD8 T lymphocytes, IL-17 CD8 T lymphocytes, myeloid dendritic cells and proinflammatory chemokines. Furthermore, HPV-positive tumors had significantly lower expression of mRNA and higher expression of PD1 mRNA compared to HPV-negative tumors. The presence of a high level of intratumoral immune cell infiltrates might play a crucial role in the significantly better response of HPV-positive patients to standard therapy and their favorable clinical outcome. Furthermore, characterization of the HNSCC immune profile might be a valuable prognostic tool in addition to HPV status and might help identify novel targets for therapeutic strategies, including cancer immunotherapy.
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http://dx.doi.org/10.4161/21624011.2014.965570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368144PMC
January 2015

Cervical cancer: what is the optimal age for routine testing?

Future Oncol 2015 ;11(8):1137-40

Department of Obstetrics & Gynecology, 2nd Medical Faculty Charles University Prague, V uvalu 84, 150 00 Prague 5, Czech Republic.

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http://dx.doi.org/10.2217/fon.15.42DOI Listing
February 2016

Global genomic diversity of human papillomavirus 6 based on 724 isolates and 190 complete genome sequences.

J Virol 2014 Jul 16;88(13):7307-16. Epub 2014 Apr 16.

Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

Unlabelled: Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts and laryngeal papillomas and has been included in both the quadrivalent and nonavalent prophylactic HPV vaccines. This study investigated the global genomic diversity of HPV6, using 724 isolates and 190 complete genomes from six continents, and the association of HPV6 genomic variants with geographical location, anatomical site of infection/disease, and gender. Initially, a 2,800-bp E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6-positive samples collected for this study. Among them, 130 exhibited at least one single nucleotide polymorphism (SNP), indel, or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full. A global alignment and maximum likelihood tree of 190 complete HPV6 genomes (130 fully sequenced in this study and 60 obtained from sequence repositories) revealed two variant lineages, A and B, and five B sublineages: B1, B2, B3, B4, and B5. HPV6 (sub)lineage-specific SNPs and a 960-bp representative region for whole-genome-based phylogenetic clustering within the L2 open reading frame were identified. Multivariate logistic regression analysis revealed that lineage B predominated globally. Sublineage B3 was more common in Africa and North and South America, and lineage A was more common in Asia. Sublineages B1 and B3 were associated with anogenital infections, indicating a potential lesion-specific predilection of some HPV6 sublineages. Females had higher odds for infection with sublineage B3 than males. In conclusion, a global HPV6 phylogenetic analysis revealed the existence of two variant lineages and five sublineages, showing some degree of ethnogeographic, gender, and/or disease predilection in their distribution.

Importance: This study established the largest database of globally circulating HPV6 genomic variants and contributed a total of 130 new, complete HPV6 genome sequences to available sequence repositories. Two HPV6 variant lineages and five sublineages were identified and showed some degree of association with geographical location, anatomical site of infection/disease, and/or gender. We additionally identified several HPV6 lineage- and sublineage-specific SNPs to facilitate the identification of HPV6 variants and determined a representative region within the L2 gene that is suitable for HPV6 whole-genome-based phylogenetic analysis. This study complements and significantly expands the current knowledge of HPV6 genetic diversity and forms a comprehensive basis for future epidemiological, evolutionary, functional, pathogenicity, vaccination, and molecular assay development studies.
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http://dx.doi.org/10.1128/JVI.00621-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054425PMC
July 2014

What are the implications of human papillomavirus status in oropharyngeal tumors for clinical practice?

Curr Opin Otolaryngol Head Neck Surg 2014 Apr;22(2):90-4

aDepartment of Otorhinolaryngology and Head and Neck Surgery, Faculty of Medicine, Charles University in Prague, Motol University Hospital bDepartment of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.

Purpose Of Review: Human papillomavirus (HPV) status itself is an important and very probably the strongest prognostic factor in head and neck cancer. Because of the prognostic advantage of patients with HPV-positive cancers, the issue of the quality of life of survivors has become increasingly important. The possibility of treatment de-escalation in patients with virally induced tumors is being considered. Many challenges have to be addressed in order to integrate HPV status in the routine decision-making in patients with oropharyngeal cancer. The present review discusses the standardization of detection methods suitable for clinical use and the differences in predictive parameters between patients with HPV-positive and HPV-negative tumors.

Recent Findings: The gold standard for the identification of patients with oropharyngeal tumors etiologically linked to HPV infection is undoubtedly the detection of HPV 16 E6/E7 mRNA. The detection of a surrogate marker of active viral infection, p16ink4a, has a low sensitivity when used alone and must therefore be combined with the detection of HPV DNA or HPV-specific antibodies. The detailed knowledge of the importance of specific prognostic parameters is crucial in the choice of treatment. Nodal staging is probably much less important in HPV-positive cancers.

Summary: It is of great importance to implement standardized testing for the identification of patients with HPV-induced oropharyngeal tumors. The treatment decision models in HPV-positive tumors have to take into account the probably different prognostic value of nodal parameters. Before introducing treatment de-escalation in patients with virally induced tumors into clinical practice, more research and clinical studies are needed.
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http://dx.doi.org/10.1097/MOO.0000000000000030DOI Listing
April 2014

Human papillomavirus type-specific prevalence in the cervical cancer screening population of Czech women.

PLoS One 2013 12;8(11):e79156. Epub 2013 Nov 12.

Department of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.

Background: Infection with high-risk human papillomavirus (HPV)types has been recognized as a causal factor for the development of cervical cancer and a number of other malignancies. Today, vaccines against HPV, highly effective in the prevention of persistent infection and precancerous lesions, are available for the routine clinical practice.

Objectives: The data on the prevalence and type-specific HPV distribution in the population of each country are crucial for the surveillance of HPV type-specific prevalence at the onset of vaccination against HPV.

Methods: Women attending a preventive gynecological examination who had no history of abnormal cytological finding and/or surgery for cervical lesions were enrolled. All samples were tested for the presence of HPV by High-Risk Hybrid Capture 2 (HR HC2) and by a modified PCR-reverse line blot assay with broad spectrum primers (BS-RLB).

Results: Cervical smears of 1393 women were analyzed. In 6.5% of women, atypical cytological findings were detected. Altogether, 28.3% (394/1393) of women were positive for any HPV type by BS-RLB, 18.2% (254/1393) by HR HC2, and 22.3% (310/1393) by BS-RLB for HR HPV types. In women with atypical findings the prevalence for HR and any HPV types were significantly higher than in women with normal cytological findings. Overall, 36 different HPV types were detected, with HPV 16 being the most prevalent (4.8%). HPV positivity decreased with age; the highest prevalence was 31.5% in the age group 21-25 years.

Conclusions: Our study subjects represent the real screening population. HPV prevalence in this population in the Czech Republic is higher than in other countries of Eastern Europe. Also the spectrum of the most prevalent HPV types differs from those reported by others but HPV 16 is, concordantly, the most prevalent type. Country-specific HPV type-specific prevalences provide baseline information which will enable to measure the impact of HPV vaccination in the future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0079156PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827175PMC
September 2014

Cervical cancer screening practices in central and eastern Europe in 2012.

Acta Dermatovenerol Alp Pannonica Adriat 2013 ;22(1):7-19

Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

The burden of cervical cancer in central and eastern Europe is generally higher compared to western or northern Europe due to a history of mostly opportunistic cervical cancer screening practices and due to the strong influence of political and economic changes in post-communist transition. This article describes the current cervical cancer screening practices, organizational plans for the future, and main obstacles that need to be overcome in 16 countries in central and eastern Europe: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia and The former Yugoslav Republic of Macedonia. Unfortunately, only a few countries have managed to establish an organized and well-functioning cervical cancer screening program in recent years, whereas most countries in the region are still struggling with implementation-related issues of organized cervical cancer screening. Encouragingly, even in the countries where only opportunistic screening is performed, well-prepared plans and strategies have been established for switching to organized screening in the near future.
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January 2014

Markers of HPV infection and survival in patients with head and neck tumors.

Int J Cancer 2013 Oct 2;133(8):1832-9. Epub 2013 May 2.

Department of Otorhinolaryngology and Head and Neck Surgery, First Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czech Republic.

The purpose of this study was to determine whether changes in human papillomavirus (HPV) DNA prevalence in oral rinses and/or HPV-specific antibody levels in the sera of patients with oral/oropharyngeal cancer have prognostic significance. One hundred and forty-two patients with oral/oropharyngeal tumors were enrolled. The presence of HPV DNA was assayed in tumor tissue and oral rinses and HPV-specific antibodies were assessed in the sera. Oral rinses were collected before treatment and one year after the treatment. Sera were drawn before treatment, one month, and one year after the end of the treatment. Altogether, 59.2% of tumors were HPV positive. The presence of HPV DNA in the tumors correlated with HPV DNA positivity in oral rinses and with HPV-specific antibodies in the sera. Out of 66 patients with HPV-positive oral rinses at enrolment, 84.8% became negative at one-year follow-up, while most patients remained seropositive for HPV-specific antigens. However, the mean titers of HPV16 E6 and/or E7 antibodies at follow-up were significantly lower. Of 16 patients with recurrences at follow-up (alive on second sampling), six were positive at enrolment for HPV16 E6 and/or E7 antibodies. In five of these, no decrease in antibody levels was observed. Titers of antibodies specific for HPV16 capsid antigens did not change during the follow-up. Our data suggest that the detection of antibodies specific for the HPV 16 E6 and E7 oncoproteins may serve not only as a marker of HPV etiology, but also as a marker of recurrence and a prognostic indicator in patients with HPV-positive tumors.
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http://dx.doi.org/10.1002/ijc.28194DOI Listing
October 2013
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