Publications by authors named "Jan Klozar"

23 Publications

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Consensus recommendations from the Czech Head and Neck Cancer Cooperative Group (2019): definition of surgical margins status, neck dissection reporting, and HPV/p16 status assessment.

Cesk Patol 2021 ;57(1):53-56

The Czech Head and Neck Cancer Cooperative Group (CHNCCG) held a meeting in Tabor on 11-12 October 2019 with the aim of reaching an interdisciplinary consensus on some controversial points where international unity is absent. The meeting resulted in recommendations on resection margin size terminology (definition of terms: negative margin, close margin and positive margin) and on the adoption of terminology for neck dissections reporting according to the International Recommendation of the International Head and Neck Scientific Group and on assessment of HPV/p16 status in head and neck tumors.
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April 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

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

Otorhinolaryngology and sleep disorders.

Cas Lek Cesk 2019 ;158(5):170-174

In the field of sleep disorders, otorhinolaryngology is mainly concerned with snoring and obstructive sleep apnea (OSA). Prevalence of OSA is suggested between 14-49 % of male and 5-30 % of female population, which makes it most common sleep disorder. The treatment of choice is positive airway pressure (PAP) therapy with excellent success rate of 90 %, however many patients dont tolerate it. Sleep surgery is usually used to get off snoring and for mild cases of OSA. Most of surgical approaches has much lower effectivity than PAP therapy; however, surgery benefit is present constantly, while PAP therapy demands patients cooperation, that is why many patients still prefer sleep surgery.
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November 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

Clinical relevance of human papillomavirus outside of oropharynx.

Authors:
Jan Klozar

Curr Opin Otolaryngol Head Neck Surg 2019 Apr;27(2):80-84

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

Purpose Of Review: The role of HPV in oropharyngeal cancer is well recognized. HPV DNA is also found in a fraction of head and neck tumors outside of oropharynx but its clinical importance is unknown. The purpose of this review is to sum up the present knowledge about the prevalence and possible impact of HPV presence in head and neck tumors in nonoropharyngeal sites.

Recent Findings: The data demonstrating prevalence of HPV presence in tumors outside of oropharynx are inconsistent. However, it can be stated that it is substantially lower than in oropharynx. Most articles report the HPV DNA presence only but very few prove also the transcriptionally active viral presence. The fraction of really HPV-induced tumors is probably very small. The majority of literature shows no impact of HPV on prognosis in nonoropharyngeal locations. Also the role of high-risk HPV in malignant transformation of lesions potentially linked to malignancy like inverted papillomas, recurrent respiratory papillomatosis or laryngeal dysplasia was up to date not demonstrated.

Summary: Despite of the unknown role of HPV and lack of evidence regarding any clinical use of HPV knowledge in other than oropharyngeal tumors, further research is warranted.
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http://dx.doi.org/10.1097/MOO.0000000000000518DOI Listing
April 2019

HPV infection and P16 expression in oral and oropharyngeal cancer in Kazakhstan.

Infect Agent Cancer 2018 12;13. Epub 2018 Jan 12.

4Charles University in Prague, University Hospital Motol, Prague, Czech Republic.

Background: Human papillomavirus (HPV) is an important etiologic factor in different cancers of anogenital region and also in a fraction of head and neck cancers (HNC) particularly oropharyngeal tumors. The HPV16 genotype associated with the majority of HPV-related head and neck carcinomas. Th incidence of oropharyngeal cancer is increasing in many countries, and the rate of HPV positive tumors is about 70% in Europe and North America. Little known about the prevalence of HPV in HNC in Central Asia.

Methods: It's a prospective analysis of patients with verified oral or oropharyngeal cancer. Sociodemographic and clinical data obtained on admission to treatment. The diagnosis of HPV positivity assessed by both the P16 expression on immunohistochemistry(IHC) and polymerase chain reaction (PCR)with HPV DNA detection and HR HPV type determination.

Results: Seventy six patients with oral and oropharyngeal cancer tested for HPV. Forteen cases were positive for HPV by PCR and 15 cases by P16 IHC. Of the 35 oropharyngeal tumors, nine were HPV DNA and p16 IHC positive, giving the rate of 25.7%. Of the 41 oral tumors, five were HPV DNA and six p16 IHC positive, giving the rate of 12.2%.

Conclusion: It is the first study mapping prevalence of HPV positivity in oral and oropharyngeal cancer in the Central Asian region. The rate of HPV positivity was higher in oropharyngeal than in oral cancer, the nonsmokers were significantly more frequent in the HPV positive group and HPV 16 was the most frequent type. However, the HPV positivity rates are lower than referred in the western world.
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http://dx.doi.org/10.1186/s13027-018-0175-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767046PMC
January 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

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

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

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

Combined bipolar radiofrequency surgery of the tongue base and uvulopalatopharyngoplasty for obstructive sleep apnea.

Arch Med Sci 2013 Dec 29;9(6):1097-101. Epub 2013 Nov 29.

Department of Otorhinolaryngology and Head and Neck Surgery, 1 Faculty of Medicine, Charles University, Faculty Hospital Motol, Prague, Czech Republic.

Introduction: The aim of the study was to investigate the effectiveness of combined bipolar radiofrequency surgery of the tongue base (RFBT) and uvulopalatopharyngoplasty (UPPP) in a single session for obstructive sleep apnea and whether this combination is safe and well tolerated.

Material And Methods: Seventy-nine patients with obstructive sleep apnea and both palatal and retroglossal obstruction underwent UPPP with bipolar RFBT. The control group consisted of 35 patients treated by UPPP alone.

Results: The apnea-hypopnea index significantly decreased from 28.7 to 14.1. The oxygen desaturation index decreased from 15.1 to 10.3. Mean oxygen saturation was unchanged. Subjectively, the Epworth Sleepiness Scale was significantly improved from 10.6 to 7.3, and the snoring level decreased from 8.4 to 6.0. The overall treatment success rate increased from 41.9% for UPPP alone to 51.7% for UPPP + RFBT. No serious adverse events occurred. Two patients had postoperative bleeding from the tonsillar bed after UPPP. Four patients had ulceration of the base of the tongue after RFBT with spontaneous cure. One patient had a taste change in half of the tongue that resolved within two months.

Conclusions: Combined bipolar RFBT and UPPP in a single session is well tolerated and safe surgery in the treatment of obstructive sleep apnea. It is effective in reducing respiratory parameters and subjective symptoms of obstructive sleep apnea. Further advantages are a single session, simple feasibility, bipolar technique and short time of the procedure.
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http://dx.doi.org/10.5114/aoms.2013.39226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902711PMC
December 2013

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

Nodal status is not a prognostic factor in patients with HPV-positive oral/oropharyngeal tumors.

J Surg Oncol 2013 May 28;107(6):625-33. Epub 2012 Nov 28.

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

Objectives: The primary aim is to compare the prognostic parameters in patients with HPV-positive and HPV-negative tumors. The secondary aim is to compare the patterns of treatment failure between these groups.

Methods: Analysis of prognostic factors in a group of 170 patients.

Results: High-risk HPV DNA was detected in 98 cases, 72 tumors were HPV negative. Both the overall and disease-specific survival rates were better in HPV-positive patients. In patients with HPV-negative tumors, the prognostic factors in univariate analysis were pT and pN classification, tumor stage, number of positive nodes, and extracapsular spread. Stage, pT, higher pN, and number of nodes maintained statistical significance after adjustment. None of the studied prognostic factors was significant in the group of patients with HPV-positive tumors. There was a significant difference in the local--regional recurrence rates--37% in HPV-negative cases and 18% in HPV-positive cases.

Conclusion: The characteristics of the extent of the disease in general and of regional lymph node metastasis in particular are probably much less important in the prediction of the outcome of HPV-positive than of HPV-negative tumors. Improved survival of patients with HPV-positive tumors is due mostly to the difference in the local-regional failure rates.
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http://dx.doi.org/10.1002/jso.23292DOI Listing
May 2013

Complications of total laryngectomy in the era of chemoradiation.

Eur Arch Otorhinolaryngol 2012 Jan 17;269(1):289-93. Epub 2011 Apr 17.

Department of Otolaryngology, Head and Neck Surgery, 1st Faculty of Medicine, Charles University, Prague, Motol University Hospital, V úvalu 84, Praha 5, Prague 15006, Czech Republic.

As more total laryngectomies (TLE) are nowadays performed as salvage procedures, the rate of postoperative complications increases. The primary aim was to report the rates of postoperative local complications for total laryngectomy in patients with previous radiotherapy or chemoradiotherapy (RT/CRT) in comparison with primary TLE data. We attempted to identify patient- and tumor-related factors predictive of postoperative pharyngocutaneous fistula (PCF) formation. The secondary aims were to analyze the survival rate in relation to postoperative complications and to study prognostic factors of survival in TLE patients. A retrospective study was conducted in 208 patients. Logistic regression was used to determine the most significant risk factors for fistula formation. Survival was analyzed by the Kaplan-Meier method, log-rank test, and Cox multivariate regression. PCF developed in 20.7% of cases. In the group of patients with previous RT/CRT, the fistula rate was significantly higher (34%). In multivariate analysis, significant risk factors for fistula formation were previous radiotherapy or chemoradiotherapy (p = 0.02), higher N classification (p = 0.03), and procedure performed by a less experienced surgeon (p = 0.003). The survival and recurrence rates were not influenced by PCF formation. The overall survival rates were lower in patients with previous RT/CRT and in patients with lymph node involvement.
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http://dx.doi.org/10.1007/s00405-011-1598-7DOI Listing
January 2012

HPV involvement in tonsillar cancer: prognostic significance and clinically relevant markers.

Int J Cancer 2011 Jul 13;129(1):101-10. Epub 2011 Apr 13.

Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czech Republic.

The association of high-risk human papillomaviruses (HR HPVs) with tonsillar cancer (TC) has been documented. Because patients with HPV-associated tumors show better survival rates, modification of their treatment regimen is being considered. It is therefore crucial to find markers for the identification of patients whose tumors are linked to viral infection. A cohort of 109 patients with primary TC was screened for HPV DNA presence in the tumor tissues and HPV-specific antibodies in sera. Data regarding risk factors and clinical parameters were collected. Forty-five specimens were analyzed for the expression of viral E6 and E2-region mRNA, and the p16 and p53 protein expression status was assessed by immunohistochemistry. The overall prevalence of HPV DNA in TC tissues was 65.1%. Ninety-three percent of HR HPV DNA-positive samples expressed E6*I mRNA. E2-region mRNA expression was detected in 36% of positive samples, which implies that the virus is integrated in 64% of HPV DNA/RNA-positive tumors. p16 overexpression and the presence of antibodies specific to HPV16 E6/E7 oncoproteins correlated well with HPV DNA and RNA presence. The disease-specific survival rate of patients with HPV DNA-positive tumors was significantly higher than that of HPV DNA-negative patients. In addition to providing further evidence of the involvement of HPV infection in the etiopathogenesis of a proportion of TC cases, our study demonstrates that p16 immunostaining and anti-E6/E7 antibodies as surrogate markers of HPV involvement represent specific, sensitive and clinically accessible assays for the identification of TC patients who have a considerably better prognosis.
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http://dx.doi.org/10.1002/ijc.25889DOI Listing
July 2011

Human papillomavirus in head and neck tumors: epidemiological, molecular and clinical aspects.

Wien Med Wochenschr 2010 Jun;160(11-12):305-309

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

High-risk types of human papillomaviruses (HR HPV) play an important role in the etiology of a group of head and neck squamous cell cancers (HNSCC). This review is focused on epidemiological, molecular, and clinical aspects of HPV infection in head and neck cancer. High risk HPV DNA is being detected in a very different proportion of HNSCC with the highest prevalence in oropharynx. Patients with HPV-associated tumors are characterized by moderate tobacco and alcohol consumption. Some aspects of sexual behavior may represent a risk factor. Recently, it has been shown that HPV infection is spreading and the rising prevalence of HPV-positive tumors can probably be attributed to this epidemic. On molecular level the viral oncoproteins E6 and E7 were shown to be involved in oncogenesis. HPV-positive cancers have better prognosis and HPV status should be considered in clinical decision-making. The rising proportion of HPV-positive tumors underlines the importance of HPV vaccination also for the prevention of HNSCC.
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http://dx.doi.org/10.1007/s10354-010-0782-5DOI Listing
June 2010

Transoral and combined transoral-transcervical approach in the surgery of parapharyngeal tumors.

Eur Arch Otorhinolaryngol 2010 May 28;267(5):765-72. Epub 2009 Aug 28.

Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Faculty Hospital Motol, Charles University, V Uvalu 84, 15006 Prague 5, Czech Republic.

The goal of parapharyngeal space (PPS) tumor surgery is to obtain adequate visualization to ensure complete removal with preservation of the surrounding nerves and vessels. Different surgical approaches have been described. Transoral approach is the most controversial one due to cited limited exposure, risk of tumor spillage, and possibility of neurovascular injury. We performed retrospective analysis of 26 consecutive patients who had undergone transoral or combined transoral-transcervical resection of PPS tumors from January 1997 to December 2007. Both approaches were safely employed to remove selected PPS tumors. Majority of treated tumors were pleomorphic adenomas (14 minor salivary gland and 7 deep lobe parotid gland tumors). Two cases of malignant salivary gland tumors, 4 nerve sheath tumors and 1 lymphangioma were also excised. Mean tumor size was 6.1 cm (range 2-11 cm). Visualization was felt to be adequate and dissection safe. Radical resection was achieved in 24 cases. Near-total resection was achieved in two cases where otherwise other approach would be suitable but cannot be undertaken because of patient refusal and comorbidities. Patients with malignant tumors had postoperative radiotherapy. Radically treated cases are disease free. One of the near-totally resected tumors needed revision surgery. Neither major complications nor disordered healing were observed. Transoral approach provides access to selected cases of PPS tumors based on preoperative imaging methods and fine-needle aspiration cytology. Risk of non-radical resection is acceptable. It can be combined with external approach to achieve safe resection of some benign tumors which would need transmandibular approach.
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http://dx.doi.org/10.1007/s00405-009-1071-zDOI Listing
May 2010

Demographic and risk factors in patients with head and neck tumors.

J Med Virol 2009 May;81(5):878-87

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

The association between human papillomavirus (HPV) infection and the development of head and neck cancer has been documented recently. In this study on 86 head and neck cancer patients and 124 controls, data regarding demographics, behavioral risk factors, and risks related to HPV exposure were collected. HPV detection was carried out using polymerase chain reaction in the tumors and in oral exfoliated cells, and HPV typing by a reverse line blot assay specific for 37 HPV types. Sera were tested by an enzyme-linked immunosorbent assay specific for HPV proteins. Head and neck cancer cases report significantly more oral-anal contact (P = 0.02) and tobacco and alcohol use than controls (P = 0.001; P = 0.02, respectively). High-risk HPV DNA was detected in 43% of oral washings of cases and 4% of controls (P < 0.0001). The association between the presence of high-risk HPV DNA in oral exfoliated cells and in tumor tissues was statistically significant (adjusted P < 0.0001). The prevalence of HPV-specific antibodies was significantly higher in cases than in controls (adjusted P < 0.0001). These results provide epidemiological and immunological evidence for HR HPV as a strong risk factor (OR = 44.3, P < 0.0001) for head and neck cancer, even after controlling for age, tobacco and alcohol use. The detection of high-risk HPV DNA in oral exfoliated cells and HPV-specific antibodies in serum can be considered as clinically relevant surrogate markers for the presence of a HPV-associated head and neck cancer, with a high sensitivity (83%) and specificity (88%).
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http://dx.doi.org/10.1002/jmv.21470DOI Listing
May 2009

Consensus recommendations for cervical cancer prevention in the Czech Republic: a report of the International Conference on Human Papillomavirus in Human Pathology (Prague, 1-3 May 2008).

J Med Screen 2008 ;15(4):207-10

National Reference Laboratory for Papillomaviruses, Department of Experimental Virology, Institute of Haematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague, Czech Republic.

A comparison of cervical cancer incidence and mortality in the Czech Republic with that from other countries shows that the burden of cervical cancer here is considerably higher than in Western Europe, where screening is widespread. In May 2008, the International Conference on Human Papillomavirus in Human Pathology was convened to review the latest evidence and to formulate consensus recommendations for the reduction of cervical cancer rates. The Czech Republic is spending considerable resources on cervical cancer prevention, but these resources are being used inefficiently. The current system is characterized by a lack of coordination and monitoring that leads to the over-screening of a minority of women while the majority of the target population are under-screened or not screened at all. It was recommended that a comprehensive, organized programme be implemented, coordinated by an independent administrative body with legal and budgetary responsibility. As the laboratory infrastructure and professional technical skills required for a quality-assured organized screening programme are already in place, implementation of this programme would not require much in the way of additional resources to produce substantial cost-effective reductions in cervical cancer rates.
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http://dx.doi.org/10.1258/jms.2008.008057DOI Listing
March 2009

HPV status and regional metastasis in the prognosis of oral and oropharyngeal cancer.

Eur Arch Otorhinolaryngol 2008 Jul 20;265 Suppl 1:S75-82. Epub 2007 Dec 20.

Department of Otolaryngology Head and Neck Surgery, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.

Prognostic factors are important for treatment decisions as they help adapt the therapy on a case-to-case basis. Nodal status, number of positive nodes, and presence of extracapsular spread are considered to be the important prognostic factors in head and neck cancer. Some studies suggest that human papillomavirus (HPV) status also influences the outcome of the treatment. This influence can be explained by the variation in tendency to develop regional metastases and by variation in the type of neck node involvement. The study objectives were to compare patients with HPV positive and HPV-negative tumors for survival and prevalence and type of regional metastasis, to identify prognostic factors and to test whether HPV presence is an independent factor of survival. The study included 81 patients treated by surgery including neck dissection for oral or oropharyngeal squamous cell cancer. A computerized medical report was completed for each patient. Analysis of the tumor specimen for the HPV DNA presence was done on paraffin-fixed tissue. HPV DNA detection and typing were performed by PCR with GP5+/GP6+BIO primers and reverse line blot hybridization. Overall, 64% (52/81) of tumors were HPV positive with 80% in the tonsillar site. HPV-positive patients had significantly better both overall (73 vs. 35%) (P=0.0112) and disease-specific (79 vs. 45%) (P=0.0015) survival rates than HPV-negative patients. No significant differences were found in the pN classification, in the number of positive nodes and the presence of extracapsular spread in the involved nodes between HPV positive and HPV-negative tumors. Multivariate analysis showed that significant prognostic factors of survival were the presence of HPV in the tumor, extracapsular spread and tumor size. HPV was the most significant prognostic factor in the studied group of patients with oropharyngeal tumors (HR=0.27, 95%CI 0.12-0.61) and possibly should be considered in treatment decisions.
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http://dx.doi.org/10.1007/s00405-007-0557-9DOI Listing
July 2008

Effectiveness and side effects of one-stage laser-assisted uvuloplasty in primary rhonchopathy.

ORL J Otorhinolaryngol Relat Spec 2007 22;69(5):316-21. Epub 2007 Aug 22.

Department of Otolaryngology, Head and Neck Surgery, First Medical Faculty, Charles University, Prague, Czech Republic.

The aim of this study is to evaluate the results of laser-assisted uvuloplasty (LAUP) in terms of effect on snoring and side effects. The case report study is based on the analysis of questionnaires with a visual analog scale (VAS) describing the severity of snoring before and 6-26 months after operation and questions regarding postoperative course. The group of patients consisted of 73 patients with primary rhonchopathy. The average preoperative VAS score was 8.36; it decreased to an average of 3.98 postoperatively (p = 0.001). No improvement was reported by 12% of patients, improvement of 4 and more of the VAS scale was reported by 67% of patients. The majority (58%) of patients reported postoperative pain for up to 10 days. Bothersome sensations persisted in 15% of patients. No predictive factors for the success of treatment were found. LAUP diminished snoring in 88% of patients. A major drawback was the postoperative pain. Further studies looking for predictive factors are needed.
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http://dx.doi.org/10.1159/000107574DOI Listing
December 2007
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