Mario Poljak

University of Ljubljana, Lubliano, Ljubljana, Slovenia

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Publications (236)568.09 Total impact

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    ABSTRACT: The aims of our study were to determine the prevalence of the babA2 gene within Helicobacter pylori strains circulating in the Slovenian pediatric population, to further clarify its significance in causing inflammation of gastric mucosa in children and to verify whether cagA, vacA, iceA and babA genes work independently or synergistically in causing gastritis. A total of 163 H. pylori isolates obtained from the same number of children were tested for the presence of cagA, vacA and iceA genes using previously established methods, while the babA2 gene was determined using novel polymerase chain reaction assay targeting a 139-bp fragment of the central region of babA2. The babA2 gene was detected in 47.9 % of H. pylori samples. The presence of the babA2 gene was strongly associated with cagA, vacA s1 and vacA m1 genotype. The babA2 status correlated positively with bacterial density score, activity of inflammation and chronic inflammation of gastric mucosa. No significant correlation was found between the babA2 status and the presence of atrophy or intestinal metaplasia. In addition, the activity of gastric inflammation and density score were significantly associated with the coexpression of the cagA, vacA s1, vacA m1 and babA2 genes. The study, which included the largest number of pediatric H. pylori samples to date, confirmed that babA2 gene plays an important role in the pathogenesis of H. pylori gastritis in children. Furthermore, our results suggest that babA2, cagA and vacA s1 and m1 gene products may work synergistically in worsening the inflammation of gastric mucosa.
    Antonie van Leeuwenhoek 07/2014; · 2.07 Impact Factor
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    ABSTRACT: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program.
    BMC Infectious Diseases 07/2014; 14(1):407. · 3.03 Impact Factor
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    ABSTRACT: It has been shown for hepatitis C virus (HCV) infection that host miRNAs contribute to the replication of the viral RNA genome. However, the clinical impact of these and many other cellular miRNAs on HCV in humans is still largely unclear. We therefore analysed the expression of miR-122, miR-126, miR-181a and miR-136 in HCV-infected patients. The study included liver biopsies of 65 patients infected with HCV of different genotypes (gt 1, gt 1a, gt 1b, gt 3 and gt 4) and nine noninfected individuals. Expression analysis of miRNAs was performed by qPCR, and they were analysed for differences between patient gender and age, genotypes, stage of fibrosis, grade of inflammation, serum level of liver enzymes, serum viral load, the presence of steatosis and mode of transmission. Different target prediction algorithms were used to search for targets of analyzed miRNAs. Statistical analysis revealed significant up-regulation of miR-136 and down-regulation of miR-126 and miR-181a in patients infected with HCV of different genotypes compared with noninfected individuals. The same expression pattern was observed in different stages and grades of liver disease. miR-122 was up-regulated in women relative to men and associated to portal inflammation, miR-122 and miR-126 correlated with serum HCV load and miR-136 and miR-122 correlated with the presence of steatosis. miR-126 and miR-136 were differentially expressed between different modes of HCV transmission. There were approximately 2000 different targets predicted for all four miRNAs and each of the analyzed miRNAs could be involved in more than a 100 different biochemical pathways. miR-122, miR-126, miR-136 and miR-181a have been shown to be involved in HCV infection with different genotypes. Their expression has been associated with the gender, stage and grade of liver disease, mode of transmission, serum HCV load and the presence of steatosis. Numerous target genes and biochemical pathways are predicted for each of the analyzed miRNAs. All these results suggest their role in HCV-infected liver disease.
    Journal of Viral Hepatitis 07/2014; · 3.08 Impact Factor
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    ABSTRACT: Cervical infections with non-high-risk human papillomavirus (non-HR-HPV) types have been associated with genital warts and a fraction of atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. The pre-vaccination prevalence of cervical infections with 25 non-HR-HPV types has been estimated, regardless of and without the coexistence of infection with HR-HPV types among Slovenian women 20-64 years old in cervical cancer screening, overall and according to age and cytology result. One thousand cervical specimens selected randomly from 4,455 specimens collected in 2010 in the Slovenian HPV prevalence survey were tested with Linear Array HPV Genotyping Test. Prevalence of cervical infections with any of the 25 non-HR-HPV types was 10.0% (95% CI: 8.1-11.9%) and with exclusively non-HR-HPV types 4.5% (95% CI: 3.2-5.8%). Prevalence of infections with any non-HR-HPV types among women with normal cytology was 8.8%, with atypical squamous cells of undetermined significance 30.4%, with low-grade squamous intraepithelial lesions 60.0%, and with high-grade squamous intraepithelial lesions 7.7%. Non-HR-HPV types without coexisting HR-HPV types were found in 4.0% of women with normal cytology, 26.1% with atypical squamous cells of undetermined significance, 6.7% with low-grade squamous intraepithelial lesions, and none with high-grade squamous intraepithelial lesion. Non-HR-HPV type cervical infections without coexisting HR-HPV infections were common among Slovenian women in cervical cancer screening with atypical squamous cells of undetermined significance, while rare in those with low-grade squamous intraepithelial lesions or worse. J. Med. Virol. © 2014 Wiley Periodicals, Inc.
    Journal of Medical Virology 06/2014; · 2.37 Impact Factor
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    ABSTRACT: In the case of an aggressive course of recurrent respiratory papillomatosis (RRP), adjuvant therapy can be used besides surgery. The aim of the study was to investigate the influence of vaccination with a quadrivalent vaccine against human papilloma viruses (HPV) types 6, 11, 16 and 18 on the course of RRP. Eleven subjects aged 13-46 years with a rapid growth of laryngeal papillomas were included in the study. They were vaccinated with three doses of the quadrivalent prophylactic HPV vaccine (Silgard(®), MSD) and followed up for 12-52 months. The intervals between the successive surgical procedures, the extension of the disease (Derkay score) at each surgery, and the number of surgical procedures per year before vaccination and after its completion were compared. The mean interval between the surgical procedures was 271.2 days before the vaccination and 537.4 days after it (p = 0.034). The mean number of surgeries per year was 2.16 before the vaccination and 0.93 after it (p = 0.022). The Derkay score did not change significantly after vaccination. Complete remission of the disease was observed in one patient, partial response to the vaccination was observed in seven patients and no response was observed in three patients. In conclusion, vaccination with the quadrivalent HPV vaccine can favorably influence the course of RRP in patients with the rapid growth of the papillomas. It significantly prolongs the intervals between the surgical procedures and reduces the number of procedures needed in the majority of patients. The present investigation can serve as a pilot study for further research. For a final conclusion a longer follow-up and studies on more patients are necessary.
    06/2014;
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    ABSTRACT: Introduction: Since the introduction of highly active antiretroviral therapy, chronic hepatitis C has become one of the leading causes of non-AIDS-related morbidity and mortality in patients with HIV infection. Two previous Slovenian nationwide studies published in 2002 and 2009 showed a very low prevalence of hepatitis C virus (HCV) infection among Slovenian HIV-infected individuals (14.5% and 10.7%, respectively). Methods and results: The presence of HCV infection was tested in 579/639 (90.6%) patients that were confirmed as HIV-positive in Slovenia by the end of 2013. Among them, 7.6% (44/579) of HIV-infected individuals were anti-HCV-positive, and 33/44 (75%) anti-HCV-positive patients were also HCV RNA-positive. HCV genotype 1 was most prevalent among HIV-infected patients (68%), followed by genotype 3 (20%), genotype 4 (8%), and genotype 2 (4%). Anti-HCV positivity was significantly higher in those that acquired HIV by the parenteral route (91.8%) than in those that acquired HIV by the sexual route (2.8%). Discussion: Slovenia remains among the countries with the lowest prevalence of HCV infection in HIV-infected individuals. Because the burden of HIV among men who have sex with men in Slovenia is disproportionately high and increasing rapidly, the current favorable situation could change quickly and should be therefore monitored regularly.
    Acta dermatovenerologica Alpina, Pannonica, et Adriatica. 06/2014; 23(2):25-6.
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    ABSTRACT: Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA25 system (version 1). A subset of 116 cancers was further tested for p16(INK4a) expression, a cellular surrogate marker for HPV-associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer dataset. HPV DNA was detected in 88.3% of anal cancers (95%CI: 85.1-91.0%) and in 95.3% of AIN 2/3 (95%CI: 84.2-99.4%). Among cancers, the highest prevalence was observed in warty-basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16(INK4a) overexpression was found in 95% of HPV DNA positive anal cancers. In view of HPV DNA results and high proportion of p16(INK4a) overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 05/2014; · 6.20 Impact Factor
  • M. Poljak, R. Norrby
    Clinical Microbiology and Infection 05/2014; 20(s5). · 4.58 Impact Factor
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    ABSTRACT: 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 global genomic diversity of HPV6 on 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. Out of them, 130 exhibited at least one single nucleotide polymorphisms (SNP), indel or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full-length. A global alignment and maximum likelihood tree of 190 HPV6 complete genomes (130 fully sequenced in this study and 60 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 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 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, 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. This study established the largest database of globally circulating HPV6 genomic variants and contributed a total of 130 new HPV6 complete 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 L2 gene 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.
    Journal of Virology 04/2014; · 5.08 Impact Factor
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    ABSTRACT: BACKGROUND: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported. METHODS: HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression. RESULTS: From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (<1 year) (p<0.001). The prevalence of TDRM was highest in MSM (prevalence of 11.1%), followed by heterosexuals (6.6%) and IDU (5.1%, p<0.001). TDRM was predominantly ascribed to nucleoside reverse transcriptase inhibitors (NRTI) with a prevalence of 6.6% in MSM, 3.3% in heterosexuals and 2.0% in IDU (p = 0.001). A significant increase in resistance to non- nucleoside reverse transcriptase inhibitors (NNRTIs) and a decrease in resistance to protease inhibitors was observed in MSM (p = 0.008 and p = 0.006, respectively), but not in heterosexual patients (p = 0.68 and p = 0.14, respectively). CONCLUSIONS: MSM showed to have significantly higher TDRM prevalence compared to heterosexuals and IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the therapy response of first-line therapy, as most include NNRTI drugs.
    PLoS ONE 04/2014; 9(4):e94495. · 3.73 Impact Factor
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    ABSTRACT: Increased life expectancy of human immunodeficiency virus (HIV)-infected patients appears to be coupled with increased incidence of cardiovascular disease (CVD). The aim of our study was to determine the presence of early atherosclerosis among Slovenian HIV-infected patients below the age of 55 years. A total of 86 HIV-infected male patients below the age of 55 years participated in our study. Ankle-brachial index (ABI) was measured using a handheld Doppler ultrasonic probe and a blood pressure cuff. Carotid intima-media thickness (CIMT) was assessed by the B-mode high-resolution ultrasound technique. Low ABI, CIMT > 0.8 mm or presence of carotid plaques were considered markers of early atherosclerosis. Average CIMT was lowest among treatment-naïve patients (0.65 mm); 10 (38.4 %) had CIMT > 0.8 mm, and carotid plaques were detected in 1 (3.8 %). Average CIMT among treated patients was 0.71 mm; 30 (50.0 %) had CIMT > 0.8 mm, and plaques were detected in 11 (18.3 %). Low ABI (≤ 0.90) was found in five patients (5.8 %) without symptoms of peripheral artery disease; two were treatment-naïve, and three received antiretroviral therapy. Early atherosclerosis was found in 43 (50.0 %) patients; 10 (38.4 %) were in treatment-naïve and 33 (55.0 %) in the treated group. Increased prevalence of early atherosclerosis among Slovenian HIV-infected patients below the age of 55 years has been demonstrated. Screening for early atherosclerosis should be implemented in the evaluation of young HIV-infected patients because a more aggressive treatment approach, aimed to delay the progression of atherosclerosis, may be warranted especially when carotid plaques are detected. We have shown that although ABI contributes to CVD risk assessment, CIMT assessment remains the more sensitive method.
    Wiener klinische Wochenschrift 03/2014; · 0.81 Impact Factor
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    ABSTRACT: The current state in the field of classifying oral and laryngeal precursor lesions, as proposed in the WHO 2005 Blue Book is not ideal. The results of various inter-observer studies have shown that the currently used grading systems, with different basic concepts and different terminology, cannot continue to be reliably used in the future. The different etiology of cervical and head and neck precursor lesions requires a classification designed to cater to the specificities of the head and neck region. Trying to harmonize different classifications of the oral and laryngeal precursor lesions, we have proposed four crucial steps to set up a unified classification of squamous intraepithelial lesions (SILs): (a) the classification should contain two grades, low-grade and high-grade lesions and, specifically for the larynx, an additional grade-carcinoma in situ (CIS) which must be separated from high-grade laryngeal SILs; (b) the terminology should be unified; our preference is for the term SIL over squamous intraepithelial neoplasia; (c) all leading morphological criteria for low- and high-grade lesions, as well as for CIS, should be clearly defined; (d) agreement between clinicians and pathologists should be achieved on the most appropriate choice of treatment of different grades of SILs in separate head and neck areas.
    Head and Neck Pathology 03/2014;
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    ABSTRACT: We report the complete genomic sequence of Phodopus sungorus papillomavirus type 1 (PsPV1), isolated from an anogenital lesion of a Siberian hamster. PsPV1 is taxonomically classified in the genus Pipapillomavirus and is most closely related to Mesocricetus auratus papillomavirus 1 (MaPV1).
    Genome announcements. 01/2014; 2(2).
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    ABSTRACT: Background Betapapillomaviruses (β-PV) are etiologically associated with epidermodysplasia verruciformis and a proportion of skin precancerous lesions and cancer, mainly in immunocompromised individuals. Objectives The prevalence and persistence of anal β-PV infection and β-PV type distribution were determined in a cohort of men who have sex with men (MSM). A correlation with HIV-1 infection status and selected demographic and behavioral risk factors were additionally established. Study design A total of 181 anal swabs (135 initial and 46 follow-up swabs) obtained from 135 Slovenian MSMs (17.0% HIV-1 positive) were tested for the presence of 25 different β-PV types using Diassay RHA Kit Skin (beta) HPV assay and, if negative, with an in-house nested Ma/Ha PCR. Results β-PVs were detected in 88/135 (65.2%) initial anal swabs. Infection with multiple β-PV types was found in 26 samples; the number of β-PVs ranged from 2 to 9. A total of 29 distinct β-PVs were detected: HPV-36 and HPV-38 were the most prevalent, followed by HPV-23, HPV-24, and HPV-93. HIV-1 positive status, promiscuity and use of alkyl nitrites were significantly associated with a higher prevalence of anal β-PV infection. Three partial DNA sequences suggesting putative new HPV types were identified. Conclusion To the best of our knowledge, this is the first study to investigate and characterize β-PV infections in the anal region. We showed that anal β-PV infection is highly prevalent in the MSM population and that β-PVs can establish persistent infection in the anal region for up to 4.8 years.
    Journal of Clinical Virology. 01/2014;
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    ABSTRACT: Human papillomaviruses (HPV) are the most frequently sexually transmitted viruses and etiological agents of several human cancers. Controversial results of the role of HPV in infertile population on sperm parameters have been published. The aim of this study was to estimate the type-specific prevalence of HPV DNA infection of the external genitalia and semen in 340 Slovenian men from infertile couples and to establish the relationship between seminal HPV DNA infection and abnormal sperm parameters. Self-taken swabs of the entire penile surface and semen samples were collected, and HPV detection and genotyping were performed. HPV DNA was detected in 37.12% of external genitalia and in 13.61% of semen samples with high HPV type concordance of both sampling sites. The most prevalent HPV types in the male external genitalia were HPV-CP6108 and HPV-84. The most prevalent HPV types in semen were HPV-53 and HPV-CP6108. The prevalence of HPV infection between normozoospermic men and men with abnormal sperm parameters did not differ significantly. Sperm quality did not differ significantly between men with seminal HPV infection and uninfected men. In conclusion, the men from infertile couples are equally susceptible to HPV infection regardless of their fertile potential; seminal HPV infection does not impair sperm quality.
    BioMed research international. 01/2014; 2014:956901.
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    ABSTRACT: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported. HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression. From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (<1 year) (p<0.001). The prevalence of TDRM was highest in MSM (prevalence of 11.1%), followed by heterosexuals (6.6%) and IDU (5.1%, p<0.001). TDRM was predominantly ascribed to nucleoside reverse transcriptase inhibitors (NRTI) with a prevalence of 6.6% in MSM, 3.3% in heterosexuals and 2.0% in IDU (p = 0.001). A significant increase in resistance to non- nucleoside reverse transcriptase inhibitors (NNRTIs) and a decrease in resistance to protease inhibitors was observed in MSM (p = 0.008 and p = 0.006, respectively), but not in heterosexual patients (p = 0.68 and p = 0.14, respectively). MSM showed to have significantly higher TDRM prevalence compared to heterosexuals and IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the therapy response of first-line therapy, as most include NNRTI drugs.
    PLoS ONE 01/2014; 9(4):e94495. · 3.73 Impact Factor
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    ABSTRACT: We present a review of current cervical cancer screening practices, the implementation status of vaccination against human papillomaviruses (HPV) and available data concerning the burden of HPV infection and HPV type-specific distribution in 16 Central and Eastern European countries: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia and the Former Yugoslav Republic (FYR) of Macedonia. Since published data were relatively scarce, two detailed surveys were conducted during August-October 2011 and in January 2013 to obtain relevant and updated information. The mean prevalence of HPV infection in 8610 women with normal cervical cytology from the region was 12.6%, with HPV16 being the most frequent HPV type. The overall HPV DNA prevalence in women with high-grade cervical lesions was 78.1%. HPV DNA was found in 86.6% of cervical cancers; the combined prevalence of HPV16/18 among HPV positive cases was 87.5%. The overall HPV DNA prevalence in genital warts and laryngeal papillomas was 94.8% and 95.2%, respectively, with HPV6 and HPV11 being the most frequent types. Opportunistic and organized cervical screening, mainly based on conventional cytology, is performed in nine and seven countries in the region, respectively, with the proposed age of the start of screening ranging from 20 to 30 years and the estimated coverage ranging from a few percent to over 70%. At least one of the current HPV prophylactic vaccines is registered in all Central and Eastern European countries except Montenegro. Only Bulgaria, Czech Republic, FYR Macedonia, Latvia, Romania and Slovenia have actually integrated HPV vaccination into their national immunization programme and currently provide routine vaccination free of charge to the primary target population. The key reasons for lack of implementation of HPV vaccination into the national immunization programme are high vaccine cost and negative public perception. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Central and Eastern Europe and Central Asia Region" Vaccine Volume 31, Supplement 7, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.
    Vaccine 12/2013; 31S7:H59-H70. · 3.77 Impact Factor

Publication Stats

2k Citations
568.09 Total Impact Points

Institutions

  • 1997–2014
    • University of Ljubljana
      • • Institute of Microbiology and Immunology
      • • Institute of Pathology
      Lubliano, Ljubljana, Slovenia
  • 2013
    • University of Latvia
      • Faculty of Medicine
      Riga, Riga, Latvia
    • Statens folkhälsoinstitut
      Östersund, Jämtland, Sweden
    • Slovenia Medical
      Maribor, Maribor, Slovenia
  • 2012
    • Splošni bolnišnici Slovenj Gradec
      Windischgraz, Slovenj Gradec, Slovenia
  • 2011
    • Albert Einstein College of Medicine
      New York City, New York, United States
    • National Forensic Laboratory Slovenia
      Lubliano, Ljubljana, Slovenia
  • 1996–2011
    • Ljubljana University Medical Centre
      • • Clinic of Otorhinolaryngology and Cervicofacial Surgery
      • • Department of Maxillofacial and Oral Surgery
      Lubliano, Ljubljana, Slovenia
  • 1998–2007
    • Zagreb University Hospital for Infectious Diseases
      Zagrabia, Grad Zagreb, Croatia