No abstract

The long control region (LCR) and the E2 protein of human papillomaviruses (HPV) are the most important viral factors regulating transcription of the viral oncogenes E6 and E7. Sequence variation within these genomic regions may have an impact on the oncogenic potential of the virus. Sequence variation in the LCR and in the E2 gene of human papillomavirus type 16 (HPV-16) isolates originating from cervical cancer patients from East Hungary was studied. In 30 samples, sequencing and/or single-strand conformation polymorphism analysis revealed variants belonging to the European variant lineage of HPV-16. These variants differed from the reference European clone only slightly in their E2 and LCR sequences. Three samples represented variants belonging to the Asian-American group. These differed from the published reference sequence at several positions in the LCR and E2 regions. Compared to the reference clone, the LCR clones of the European isolates showed very similar transcriptional activities, while that of an Asian-American isolate had " 1n7-fold increased activity. Most of the increased activity of the Asian-American isolate could be ascribed to nucleotide changes found at the 3h end of the LCR (nt 7660-7890). The transcriptional transactivation potentials of the HPV-16 E2 isolates differed only slightly from each other, and the differences seemed to be independent of the taxonomic position of the isolates.

HPVs may be involved in the development or progression of not only OSCC but also of potentially malignant oral lesions.

We tested 65, 44, and 116 patients with oral squamous cell cancer (OSCC), oral leukoplakia (OL), and oral lichen planus (OLP) against 68 age‐matched controls for the presence of Epstein–Barr virus (EBV). Apparently healthy mucosa was simultaneously sampled and examined in all patients. Paraffin‐embedded tissue sections of all EBV‐positive patients with OSCC were examined for latent membrane protein‐1 (LMP‐1) expression (demonstrable in most EBV‐associated malignancies) using immunohistochemistry. The prevalence of EBV in the controls and in OSCC, OL, and OLP lesions was 19.1%, 73.8%, 29.5%, and 46.6%, respectively, and 66.2%, 22.7%, and 31.9% in the healthy mucosa of patients, respectively. The prevalence of EBV in OSCC patients was significantly higher than in controls or in respective samples of the other two patient groups both in the lesion and in the healthy mucosa. Comparisons including only patients with EBV‐negative lesions yielded similar results. Lesions of patients with OLP, but not of patients with OL, differed significantly from controls in EBV prevalence. In OSCC, LMP‐1 expression was not detected, and EBV carriage was not significantly associated with any risk factors and did not influence the outcome. Although a high prevalence of EBV was found in OSCC, comparable carriage rates on healthy mucosa of patients indicated that an aetiological role of EBV is unlikely.

Background: Survivin, a novel member of the inhibitor of apoptosis family, plays an important role in cell cycle regulation. A common polymorphism at the survivin gene promoter (G/C at position 31) was shown to be correlated with survivin gene expression in cancer cell lines. Aim: To investigate whether this polymorphism could be involved in the development of human papillomavirus (HPV)-associated cervical carcinoma. Methods: Survivin promoter polymorphism was detected in patients with cervical cancer, in patients with equivocal cytological atypia and in a control population using polymerase chain reaction (PCR-restriction fragment length polymorphism (RFLP) and PCR-single strand conformation polymorphism analysis. HPV was typed in patients with cervical cancer and cytological atypia using PCR-RFLP. Results: No statistically significant differences were found in the genotype distributions of the survivin promoter variants among our study groups. Conclusions: The survivin promoter polymorphism at position 31 may not represent an increased risk for the development of cervical cancer, at least in the population studied here.

Aim: To determine the prevalence, type, physical state, and viral load of human papillomavirus (HPV) DNA in cases of head and neck cancer and recurrent respiratory papillomatosis (RRP). Methods: The prevalence and type of HPV DNA was determined in 27 fresh frozen tissue specimens from patients with head and neck cancers and 16 specimens from 10 patients with RRP by MY09/MY11 and GP5+/ GP6+ nested polymerase chain reaction (PCR) and subsequent restriction enzyme cleavage. The physical state of HPV DNA was analysed by E1, E2, and E1E2 specific PCRs and Southern blot hybridisation (SBH). Results: HPV DNA was detected in 13 of 27 cancers and 10 of 10 papillomas. Both low risk HPV-6 and HPV-11 and high risk HPV-16 were present in cancers in low copy numbers, whereas papillomas exclusively harboured low risk HPV-6 and HPV-11. E1E2 PCRs failed to determine the physical state of HPV in cancers except one case where HPV-6 DNA was integrated. In contrast to cancers, all papillomas showed the episomal state of HPV DNA and a relatively higher viral load. Conclusions: Based on the prevalence, type, physical state, and copy number of HPV DNA, cancers and papillomas tend to show a different HPV DNA profile. The 100% positivity rate of low risk HPV types confirms the role of HPV-6 and HPV-11 in the aetiology of RRP.T he association of high risk human papillomavirus (HPV) types with anogenital cancers is well established. In the past two decades, several authors have detected HPV DNA in head and neck cancers by Southern blot hybridisation (SBH) or polymerase chain reaction (PCR).1-10 Among head and neck cancers, HPV DNA positivity tends to show site dependence, with the tonsils, oral cavity, and larynx being the most common sites.1 7 10 High risk HPV types 16 and 18 are by far the most predominant types at all sites.3 7 10 11 However, epidemiological data reveal that the role of HPVs in the aetiology of head and neck cancers is rather controversial: the reported frequency of HPV DNA even in the often studied laryngeal site varies between 3% and 85% in the literature. 8 In addition, the prognostic value of HPV DNA positivity is also equivocal. Recurrent respiratory papillomatosis (RRP) is the most common benign tumour of the laryngeal epithelium.12 Low risk HPV-6 and HPV-11 are the most frequently detected types and are accepted as aetiological agents in RRP. [13][14][15][16] ''The product of the E2 open reading frame has a regulatory role in the transcription of the transforming E6 and E7 viral genes'' HPV DNA may exist either in the episomal form or integrated into the host's genome. [17][18][19][20] In the episomal form, the circular double stranded papillomavirus DNA is intact. In contrast, integration results in disruption of the circular viral genome, mainly in the E1E2 open reading frames (ORFs). 21The product of the E2 ORF has a regulatory role in the transcription of the transforming E6 and E7 viral genes. Disruption of this regulatory role at integration results in increased concentrations of transforming viral proteins...

Background Increasing antibiotic resistance may reciprocally affect consumption and lead to use of broader-spectrum alternatives; a vicious cycle that may gradually limit therapeutic options. Our aim in this study was to demonstrate this vicious cycle in gram-negative bacteria and show the utility of vector autoregressive (VAR) models for time-series analysis in explanatory and dependent roles simultaneously. Methods Monthly drug consumption data in defined daily doses per 100 bed-days and incidence densities of gram-negative bacteria (Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii) resistant to cephalosporins or to carbapenems were analyzed using VAR models. These were compared to linear transfer models used earlier. Results In case of all gram-negative bacteria, cephalosporin consumption led to increasing cephalosporin resistance, which provoked carbapenem use and consequent carbapenem resistance and finally increased colistin consumption, exemplifying the vicious cycle. Different species were involved in different ways. For example, cephalosporin-resistant Klebsiella spp. provoked carbapenem use less than E. coli, and the association between carbapenem resistance of P. aeruginosa and colistin use was weaker than that of A. baumannii. Colistin use led to decreased carbapenem use and decreased carbapenem resistance of P. aeruginosa but not of A. baumannii. Conclusions VAR models allow analysis of consumption and resistance series in a bidirectional manner. The reconstructed resistance spiral involved cephalosporin use augmenting cephalosporin resistance primarily in E. coli. This led to increased carbapenem use, provoking spread of carbapenem-resistant A. baumannii and consequent colistin use. Emergence of panresistance is fueled by such antibiotic-resistance spirals.

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