Bradavice jsou benigní útvary vyskytující se na kůži, méně často na sliznicích. Nejčastěji jsou jimi postiženy děti, adolescenti a imunosuprimovaní pacienti. Příčinou vzniku jsou viry patřící do skupiny humánních papillomavirů (HPV). Klinický obraz je variabilní. Bradavice mají značný sklon k recidivám. Rozlišujeme několik typů: vulgární bradavice - verrucae vulgares, plantární bradavice - verrucae plantares, ploché bradavice - verrucae planae juvenilis, střapcovité bradavice - verrucae filliformes a genitální bradavice - condylomata accuminata.
The warts are benign lesions, which occur on the skin, rarely on the mucosa. Children, adolescents, and people with diminished resistance are mostly infected. Human papillomavirus (HPV) is responsible for many lesions. The warts tend to relapse. We differentiate several types of warts - verrucae vulgares, verrucae plantares, verrucae planea juvenilis, verrucae filliformis, and condylomata accuminata.
- MeSH
- bradavice * klasifikace přenos terapie MeSH
- lidé MeSH
- lidské papilomaviry patogenita MeSH
- primární zdravotní péče MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Penile squamous cell carcinoma (pSCC) is a rare tumour with a variable prognosis. More prognostic markers linked to mutational signatures and the tumour immune microenvironment are needed. A cohort made up of 165 invasive pSCC was retrospectively analysed using formalin-fixed, paraffin-embedded tumour tissue, focusing on tumour mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, microsatellite instability (MSI), the number of tumour infiltrating lymphocytes (TILs) expressing cytotoxic T-lymphocyte-associated protein 4 (CTLA4), HPV status determined by p16 immunohistochemistry, and several traditional histopathological variables. High TMB (>10 mut/Mb) was associated with high PD-L1 expression (TPS 50-100%), and HPV-negative status. High PD-L1 expression was linked to HPV negativity, a high number of intratumoural CTLA4+ cells, and brisk lymphocytic infiltrate. High TMB was a significant predictor of shorter overall survival (OS) in both univariate and multivariate analysis when using a median cut-off value of 4.3 mut/Mb, but not when using an arbitrary cut-off of 10 mut/Mb. Low CTLA4+ cell infiltration at the tumour invasion front was a marker of shorter OS and cancer-specific survival in both univariate and multivariate analysis. PD-L1 expression had no significant impact on prognosis. Only two cases were MSI high. The results support the hypothesis of two aetiological pathways in pSCC cancerogenesis: (1) SCC linked to HPV infection characterised by low TMB, less common PD-L1 expression, and a lower number of TILs; and (2) SCC linked to chronic inflammation leading to a high number of acquired mutations (high TMB), HPV negativity, increased neoantigen production (i.e., PD-L1), and high immune cell infiltration.
- MeSH
- antigen CTLA-4 MeSH
- antigeny CD274 metabolismus MeSH
- infekce papilomavirem * komplikace MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory penisu * genetika MeSH
- retrospektivní studie MeSH
- spinocelulární karcinom * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
High-risk human papillomaviruses (HPVs) cause various cancers. While type-specific prophylactic vaccines are available, additional anti-viral strategies are highly desirable. Initial HPV cell entry involves receptor-switching induced by structural capsid modifications. These modifications are initiated by interactions with cellular heparan sulphates (HS), however, their molecular nature and functional consequences remain elusive. Combining virological assays with hydrogen/deuterium exchange mass spectrometry, and atomic force microscopy, we investigate the effect of capsid-HS binding and structural activation. We show how HS-induced structural activation requires a minimal HS-chain length and simultaneous engagement of several binding sites by a single HS molecule. This engagement introduces a pincer-like force that stabilizes the capsid in a conformation with extended capsomer linkers. It results in capsid enlargement and softening, thereby likely facilitating L1 proteolytic cleavage and subsequent L2-externalization, as needed for cell entry. Our data supports the further devising of prophylactic strategies against HPV infections.
- MeSH
- heparitinsulfát * metabolismus chemie MeSH
- infekce papilomavirem virologie MeSH
- internalizace viru * MeSH
- kapsida * metabolismus chemie MeSH
- lidé MeSH
- lidské papilomaviry MeSH
- lidský papilomavirus 16 metabolismus fyziologie MeSH
- mikroskopie atomárních sil * MeSH
- Papillomaviridae fyziologie MeSH
- polysacharidy metabolismus chemie MeSH
- vazba proteinů MeSH
- vazebná místa MeSH
- virové plášťové proteiny * metabolismus chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- avelumab,
- MeSH
- imunoterapie metody MeSH
- lidé MeSH
- Merkelův nádor * chirurgie farmakoterapie patologie radioterapie MeSH
- metastázy nádorů patologie MeSH
- neúspěšná terapie MeSH
- progrese nemoci MeSH
- protinádorové látky imunologicky aktivní aplikace a dávkování MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
Simian virus 40 (SV40) is a monkey virus with tumorigenic potential in rodents and is associated with several types of human cancers, including lymphomas. A related Merkel cell polyomavirus causes carcinoma in humans by expressing truncated large tumor antigen (LT), with truncations caused by APOBEC family of cytidine deaminase-induced mutations. AID (activation-induced cytidine deaminase), a member of the APOBEC family, is the initiator of the antibody diversification process known as somatic hypermutation and its aberrant expression and targeting is a frequent source of lymphomagenesis. In this study, we investigated whether AID could cause mutations in SV40 LT. We demonstrate that the SV40 enhancer has strong somatic hypermutation targeting activity in several cell types and that AID-induced mutations accumulate in SV40 LT in B cells and kidney cells and cause truncated LT expression in B cells. Our results argue that the ability of the SV40 enhancer to target somatic hypermutation to LT is a potential source of LT truncation events that could contribute to tumorigenesis in various cell types, thereby linking SV40 infection with malignant development through a novel mutagenic pathway.
- MeSH
- AICDA (aktivací indukovaná cytidindeamináza) MeSH
- antigeny transformující polyomavirové genetika metabolismus MeSH
- antigeny virové nádorové genetika metabolismus MeSH
- B-lymfocyty virologie metabolismus imunologie MeSH
- buněčné linie MeSH
- cytidindeaminasa * genetika metabolismus MeSH
- infekce onkogenními viry genetika virologie MeSH
- karcinogeneze genetika MeSH
- lidé MeSH
- mutace MeSH
- opičí virus SV40 * genetika MeSH
- polyomavirové infekce genetika virologie MeSH
- somatická hypermutace imunoglobulinových genů genetika MeSH
- zesilovače transkripce * genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The optimal treatment of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) is currently a subject of clinical research. This questionnaire study investigated current trends in the treatment of HPV-associated (HPV+) OPC in Slovakia with the incorporation of deintensification of oncological treatment into routine clinical practice outside of clinical trials. The Slovak Cooperative Head and Neck Cancer Group (SCHNCG) developed a questionnaire aimed at identifying trends in the oncological treatment of HPV+ OPC intended for all radiation oncology (RO) facilities in Slovakia. Specialists in the field of RO responded to general questions about the character of their individual institutions as well as to 4 theoretical clinical scenarios (case reports) regarding the treatment of HPV+ OPC, focusing primarily on the applied dose of radiotherapy (RT), the extent of target volumes, and the type of concurrent chemotherapy (CHT). The questionnaire study involved 35 RO specialists from 14 institutions in Slovakia. Regarding primary chemoradiotherapy (CRT) in T1N1M0 HPV+ OPC, 16 respondents (45.7%) would consider de-escalation of the RT dose to <70 Gy. In the case of postoperative RT in pT1pN1M0 HPV+ OPC with negative resection margins (R0) and absent extracapsular extension (ECE), 4 physicians (11.4%) would consider de-escalation of the RT dose to <60 Gy in the tumor bed area, while the majority of the treating specialists (n=19, 54.3%) would omit concurrent CHT. In the case of primary RT in elderly patient with T2N1M0 HPV+ OPC, the same number of physicians (n=16, 45.7%) would consider de-escalation of the RT dose to <70 Gy, and 14 respondents (40.0%) would completely omit CHT. In a high-risk patient with T2N3M0 HPV+ OPC with a complete response after 3 cycles of induction chemotherapy (iCHT), none of the respondents would indicate a reduction in the RT dose to the area of the original tumor and lymphadenopathy to <60 Gy. The doses and extent of irradiated volumes in the treatment of HPV+ OPC in Slovakia vary among different institutions. The tendency to de-escalate RT doses and reduce doses of concurrent systemic therapy in Slovakia is high and there was also an observed trend to reduce the extent of radiation treatment fields.
- MeSH
- chemoradioterapie * MeSH
- infekce papilomavirem * virologie komplikace terapie MeSH
- lidé MeSH
- lidské papilomaviry MeSH
- nádory orofaryngu * virologie terapie MeSH
- Papillomaviridae MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
OBJECTIVE: The substantial material and legislative investments in establishing and maintaining cytological screening in the Czech Republic represent barriers to a direct transition to primary HPV screening. Therefore, the LIBUSE project was implemented to test the efficacy of phasing in HPV DNA testing as a co-test to cytology in routine screening of women >30 years of age. METHODS: Women aged 30 to 60 years who underwent regular annual Pap smears were co-tested for HPV DNA with selective 16/18 genotyping at 3-year intervals. All HPV 16/18-positive cases and/or cases with a severe abnormality in cytology were sent for colposcopy; HPV non-16/18-positive cases and LSILs were graded using p16/Ki67 dual-stain cytology, and positive cases were sent for colposcopy. RESULTS: Overall, 2409 patients were included. After the first combined screening (year 'zero') visit, 7.4% of women were HPV-positive and 2.0% were HPV16/18-positive; only 8 women had severe Pap smear abnormalities. Triage by dual staining was positive in 21.9% of cases (28/128). Biopsy confirmed 34 high-grade precancer lesions. At the second combined visit (year 'three'), the frequency of HPV infection (5.3% vs. 7.4%) frequency of HPV16/18 (1.1% vs. 2.0%), referrals for colposcopy (35 vs. 83), and biopsy verified high-grade lesions (5 vs. 34) were significantly lower (all P ≤ 0.001). CONCLUSION: The addition of HPV DNA testing with selective genotyping of HPV16/18 to existing cytology screening significantly increased the safety of the program. The gradual introduction of HPV testing was well received by healthcare professionals and patients, and can facilitate transformation of the cytology-based screening. ClinicalTrials.gov Identifier: NCT05578833.
- MeSH
- barvení a značení MeSH
- časná detekce nádoru MeSH
- DNA MeSH
- dospělí MeSH
- dysplazie děložního hrdla * diagnóza MeSH
- infekce papilomavirem * MeSH
- lidé MeSH
- lidský papilomavirus 16 genetika MeSH
- lidský papilomavirus 18 genetika MeSH
- nádory děložního čípku * MeSH
- Papanicolaouův test MeSH
- plošný screening MeSH
- třídění pacientů MeSH
- vaginální stěr MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.
- MeSH
- infekce papilomavirem * MeSH
- lidé MeSH
- lidské papilomaviry MeSH
- lidský papilomavirus 16 MeSH
- nádory hlavy a krku * diagnóza MeSH
- nádory orofaryngu * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
