OBJECTIVES: The aim of the EXPL-HPV-002 study is to evaluate the integration of 14 high-risk HPV as a biomarker of the severity and the progression of cervical lesions. Such a „triage biomarker“ would help to reduce the number of unnecessary colposcopies, to avoid over-treatment of lesions that spontaneously regress and to better target the lesions requiring treatment. DESIGN: EXPL-HPV-002 is a prospective, open-label, single arm, GCP study conducted at 2 clinical sites in the Czech Republic. SETTINGS: Investigations centers: Private Gynecology Center, Brno; Gynecological and Obstetrical Clinic, Brno; Genotyping central lab: NRL for Papillomaviruses and polyomaviruses, IHBT, Prague; Histology Central reading: Aeskulab Pathology, Prague; Molecular combing HPV test: Genomic Vision, Bagneux. METHODS: From June 2016 to May 2018, 688 patients aged 25-65, referred to colposcopy after an abnormal Pap-smear, were enrolled in the study. Among them 60% were found HPV high-risk. The study is divided in two phases: 1. a cross-sectional phase using data collected at first visit (colposcopy images ± histology, pap-smear for HPV genotyping and molecular combing) to study the association between HPV integration status versus colposcopy and histology grades; 2. a longitudinal phase using data collected in follow-up visits: cytology at 6, 18 and 30 months and colposcopy ± histology at 12, 24 and 36 months. A pap-smear collected at 12, 24 and 36 months allows to perform genotyping and molecular combing. HPV integration status is analyzed in comparison with the evolution of lesions, viral clearance and HPV genotype. HPV genotyping and molecular combing were performed on pap-smear samples in central laboratories. Histology data were reviewed by central reading. RESULTS: The transversal phase of the study is achieved and shows that the HPV integration into the human DNA, monitored by molecular combing, can significantly differentiate normal subjects from women with cervical lesions or cancer. CONCLUSION: HPV integration into the host genome, monitored by Genomic Visions technology, is a reliable diagnostic biomarker that will greatly help clinicians to improve their medical decision tree.

• Klíčová slova
• Genomic Morse Code, HPV diagnostic, biomarker, cervical cancer, molecular combing, viral integration,
• MeSH
• časná detekce nádoru metody   MeSH
• DNA sondy HPV MeSH
• DNA virů analýza   MeSH
• dospělí MeSH
• infekce papilomavirem diagnóza   virologie   MeSH
• kolposkopie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory děložního čípku diagnóza   prevence a kontrola   virologie   MeSH
• Papillomaviridae genetika   MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• senioři MeSH
• těhotenství MeSH
• vaginální stěr * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• DNA sondy HPV MeSH
• DNA virů MeSH

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.

• MeSH
• DNA sondy HPV MeSH
• genom virový MeSH
• infekce papilomavirem diagnóza   epidemiologie   genetika   patologie   MeSH
• lidé MeSH
• lidský papilomavirus 6 genetika   MeSH
• nádorová transformace buněk genetika   patologie   MeSH
• otorinolaryngologické nádory diagnóza   epidemiologie   genetika   patologie   MeSH
• Papillomavirus E7 - proteiny genetika   MeSH
• prognóza MeSH
• průřezové studie MeSH
• rizikové faktory MeSH
• spinocelulární karcinom diagnóza   epidemiologie   genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• DNA sondy HPV MeSH
• Papillomavirus E7 - proteiny MeSH

Parallel sections from 423 randomly selected blocks representing biopsies of 178 women with the diagnosis of cervical dysplasia and/or erosion were stained for p16 polypeptide. The p16/INK4A (inhibitory kinase 4) protein is a cellular division regulator, expression of which increases in the presence of oncoprotein E7, encoded by human papillomavirus (HPV). Expression of p16 protein was seen in the nuclei and cytoplasm of dysplastic squamous epithelium cells as well as in carcinoma cells. In 16.6% of erosion cases, the p16 antigen was present in the basal and suprabasal layer of the surrounding squamous epithelium revealing features of CIN I/LSIL. In CIN I/LSIL as classified by HE staining, the p16 antigen was found in 65 out of 80 (81%) cases. The p16 protein was typically seen in dysplastic basal and suprabasal cells encompassing a confluent layer in the lowest third segment of stratified epithelium. In CIN II and CIN III grouped as HSIL, the positive rate of p16 antigen presence was 95% (in 45 cases out of 47) and/or 100% (in each of 27 cases), respectively. The typical sign of p16 antigen distribution in HSIL was its staining over two thirds and/or throughout the whole dysplastic epithelium. Extensive staining for p16 antigen was registered within nuclei as well as cytoplasm of neoplastic cells in all 6 cervical squamous cell carcinomas, which were examined in many sections when being used as positive controls. Based on our experience, we consider the p16 antigen staining a helpful tool indicating dysplastic cells and estimating their extent.

• MeSH
• barvicí látky MeSH
• biologické markery analýza   MeSH
• DNA sondy HPV MeSH
• dysplazie děložního hrdla chemie   diagnóza   virologie   MeSH
• epitel chemie   MeSH
• hematoxylin MeSH
• histocytochemie MeSH
• inhibitor p16 cyklin-dependentní kinasy analýza   MeSH
• lidé MeSH
• nádory děložního čípku prevence a kontrola   virologie   MeSH
• prekancerózy chemie   diagnóza   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• barvicí látky MeSH
• biologické markery MeSH
• DNA sondy HPV MeSH
• hematoxylin MeSH
• inhibitor p16 cyklin-dependentní kinasy MeSH

A total of 88 samples of laryngeal lesions (23 vocal cord nodules (VCNs), 23 papillomas (PAs), 18 dysplasias (DYs), and 24 carcinomas (CAs)) were analyzed for p16INK4a protein (p16) expression by immunohistochemistry and for high-risk human papillomavirus (HR-HPV) infection using chromogene in situ hybridization (CISH) and polymerase chain reaction (PCR). The series comprised 62 males and 26 females, aged 1-87 years (median 55 years). p16 expression was detected in 2 of 23 (9%) VCNs, 18 of 23 (78%) PAs, 9 of 18 (50%) DYs, and 14 of 24 (58%) CAs. Using CISH, HR-HPV DNA was detected in 3 of 23 (13%) VCNs, in 19 of 23 (83%) PAs, in 12 of 18 (67%) DYs, and in 14 of 24 (58%) CAs. HR-HPV DNA was found in six of nine (67%) PAs by PCR. A statistically significant difference in p16 expression and HR-HPV DNA presence detected by CISH was observed between VCNs and PAs (p<0.000001). The sensitivity and specificity of p16 expression for HR-HPV DNA presence detected by CISH was 0.612 and 0.773, respectively. Our study confirms a potential role of HR-HPV infection not only in the pathogenesis of malignant, but also in benign laryngeal lesions.

• MeSH
• Alphapapillomavirus genetika   izolace a purifikace   MeSH
• dítě MeSH
• DNA sondy HPV MeSH
• DNA virů izolace a purifikace   MeSH
• dospělí MeSH
• hybridizace in situ MeSH
• imunohistochemie MeSH
• infekce papilomavirem komplikace   diagnóza   virologie   MeSH
• inhibitor p16 cyklin-dependentní kinasy analýza   MeSH
• karcinom * chemie   patologie   virologie   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• nádory hrtanu * chemie   patologie   virologie   MeSH
• papilom * chemie   patologie   virologie   MeSH
• polymerázová řetězová reakce MeSH
• předškolní dítě MeSH
• prekancerózy * chemie   patologie   virologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• DNA sondy HPV MeSH
• DNA virů MeSH
• inhibitor p16 cyklin-dependentní kinasy MeSH

The presented investigation is concerned with contemporary diagnostic possibilities of HPV Infection of the Cervix. The authors present the results of virological examinations of 228 female patients in the Centre for Oncological Prevention. The examination was made by hybridization techniques, using probes specific for HPV 6, 11, 16 and 18 and by serological methods where IgG antibodies were assessed against synthetic peptides, corresponding to several HPV epitopes, as antigens. 156 women (68.4%) were virologically positive, 72 (31.6%) were negative. Subsequently the authors investigated the diagnostic accuracy of HPV changes of the cervix by clinical methods, i.e. colposcopy and cytology, as compared with virological methods. On colposcopic examination uncertain--i.e. insignificant--results were recorded in 24.6%, on cytological examination in 19.7%. In patients where these methods gave unequivocal results (either + or-) a correct forecast of the presence of HPV during colposcopic examination was recorded in 71.1%, in cytological examinations in 66.9%. At least one of the clinical methods assessing papilloma virus infection was prognostically correct in 90.4%. From the investigation ensures that prebioptic methods provide the clinician with relatively reliable information on the presence of HPV infection and enable him to select a therapeutic and dispensarization procedure adequate to the finding. However, they cannot replace virological examination among other reasons also because they cannot assess the HPV type.

• MeSH
• cytodiagnostika MeSH
• DNA sondy HPV MeSH
• hybridizace in situ MeSH
• infekce onkogenními viry diagnóza   MeSH
• infekce papilomavirem diagnóza   MeSH
• kolposkopie MeSH
• lidé MeSH
• nemoci cervix uteri diagnóza   MeSH
• Papillomaviridae * izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• DNA sondy HPV MeSH

The DNA probes for HPV types 6, 11, 16, 18, 33 and 56 were prepared and biotinylated. They were used in hybridization in situ test for detection HPVs in the cells of 29 cervical samples with various grade of dysplasia and CIS. It was verified that DNA probes are suitable for HPV detection and that the grade of pathological changes is dependent on the presence of viral DNA. On the other hand, the pathological diagnosis of koilocytosis often do not reflect actual presence of HPV DNA in cell genome.

• MeSH
• cervix uteri patologie   virologie   MeSH
• DNA sondy HPV * MeSH
• dospělí MeSH
• hybridizace in situ MeSH
• lidé MeSH
• mladiství MeSH
• Papillomaviridae * MeSH
• zalévání tkání do parafínu MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA sondy HPV * MeSH

The epidemiology of human papillomaviruses (HPV) was studied in 61 immunocompromised patients (e.g. renal and cardiac transplants; Bowen's disease; genital cancer) undergoing therapy at the University Hospital of Wales at Cardiff U.K. Warts from various sites of these patients were studied for the presence of HPV types 6, 11, 16 and 18 using the dot-blot DNA hybridization technique. Four HPV-16 and one HPV-11 was detected. The presence of HPV-16 in our study is quite significant since it suggests the potential occurrence of genital HPV types in skin warts in immunocompromised patients and hence the need for screening such patients against HPV types. HPV, mainly types 16 and 18 are usually associated with genital cancer, cervical malignancies and cervical intraepithelial neoplasia. The semen of the husband of 30 women with cervical abnormalities and the semen of 30 husbands (control) of wives with normal cervix were tested for HPV-6, 11, 16 and 18. No HPV-DNA could be detected in all of the 60 specimen. This suggests that specimens were either truly negative for any of those types or because virus DNA could present in a small amount less than 5 pg/microliters in some patients. Whether semen plays a role in transmitting HPV is still controversial.

• MeSH
• DNA sondy HPV MeSH
• DNA virů analýza   MeSH
• imunokompromitovaný pacient * MeSH
• infekce onkogenními viry mikrobiologie   přenos   MeSH
• kondylomata akuminata imunologie   mikrobiologie   MeSH
• lidé MeSH
• nádory děložního čípku mikrobiologie   MeSH
• Papillomaviridae izolace a purifikace   MeSH
• sperma mikrobiologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA sondy HPV MeSH
• DNA virů MeSH

14 tumours in the ENT region were tested for the presence of human papillomaviruses (HPV) DNA. The dot-blot hybridization technique was used for HPV sequence detection. HPV DNA mixture of types 6b, 11, 16 and 18 served as a probe. The following five samples showed positive reaction: 3 carcinomas of the larynx, 1 carcinoma of the nasal cavity and 1 papilloma of the nasal cavity.

• MeSH
• DNA sondy HPV * MeSH
• DNA sondy * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• otorinolaryngologické nádory mikrobiologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• DNA sondy HPV * MeSH
• DNA sondy * MeSH