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

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 management and surveillance of glandular pre-cancerous lesions of the uterine cervix present distinct challenges compared with squamous lesions, primarily attributed to the lower effectiveness of diagnostic methods such as cytology or colposcopy. This study aimed to investigate the long-term safety of fertility-sparing treatment for adenocarcinoma in situ and microinvasive adenocarcinoma of the cervix, while identifying factors associated with recurrence, with a particular emphasis on the role of human papillomavirus (HPV) testing. METHODS: We retrospectively reviewed data from all patients with histopathologically confirmed adenocarcinoma in situ or microinvasive cervical adenocarcinoma who received treatment at a single center between 2002 and 2023. The study involved the examination of consecutive surgical specimens and the follow-up details. Factors associated with recurrence were assessed in a subgroup of patients with available long-term follow-up data (at least 6 months). RESULTS: In total, 143 patients (112 with adenocarcinoma in situ and 31 with adenocarcinoma) were included in the analysis. Among the 86 patients who underwent fertility-sparing treatment, the recurrence rate was 9% (12% for adenocarcinoma in situ and 4% for adenocarcinoma) during a median follow-up period of 56.6 months (range 7-179). No patients who were HPV negative experienced recurrence during the follow-up period. In contrast, among patients who were HPV positive, the recurrence rate was 38%. Additionally, HPV 16/18 positivity displayed a notable association with a higher risk of recurrence compared with the other high-risk genotypes, although this difference did not reach statistical significance (83% vs 10%; p=0.083, log-rank). CONCLUSION: Our retrospective study demonstrated a significant association between the risk of recurrence and HPV status during the follow-up period. Consequently, long-term follow-up utilizing HPV testing and genotyping appears to be a secure alternative to a hysterectomy.

• MeSH
• adenokarcinom virologie   patologie   MeSH
• dospělí MeSH
• infekce papilomavirem * diagnóza   virologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• nádory děložního čípku * virologie   patologie   diagnóza   terapie   MeSH
• následné studie MeSH
• Papillomaviridae izolace a purifikace   MeSH
• retrospektivní studie MeSH
• třídění pacientů metody   MeSH
• zachování plodnosti metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Human papillomaviruses (HPVs) represent a diverse group of double-stranded DNA viruses associated with various types of cancers, notably cervical cancer. High-risk types of HPVs exhibit their oncogenic potential through the integration of their DNA into the host genome. This integration event contributes significantly to genomic instability and the progression of malignancy. However, traditional detection methods, such as immunohistochemistry or PCR-based assays, face inherent challenges, and thus alternative tools are being developed to fasten and simplify the analysis. Our study introduces an innovative biosensing platform that combines loop-mediated amplification with electrochemical (EC) analysis for the specific detection of HPV16 integration. By targeting key elements like the E7 mRNA, a central player in HPV integration, and the E2 viral gene transcript lost upon integration, we show clear distinction between episomal and integrated forms of HPV16. Our EC data confirmed higher E7 expression in HPV16-positive cell lines having integrated forms of viral genome, while E2 expression was diminished in cells with fully integrated genomes. Moreover, we revealed distinct expression patterns in cervical tissue of patients, correlating well with digital droplet PCR, qRT-PCR, or immunohistochemical staining. Our platform thus offers insights into HPV integration in clinical samples and facilitates further advancements in cervical cancer research and diagnostics.

• MeSH
• biosenzitivní techniky metody   MeSH
• DNA vazebné proteiny genetika   MeSH
• DNA virů genetika   MeSH
• elektrochemické techniky * metody   MeSH
• genom virový MeSH
• infekce papilomavirem * virologie   MeSH
• integrace viru * genetika   MeSH
• lidé MeSH
• lidský papilomavirus 16 * genetika   MeSH
• messenger RNA * genetika   MeSH
• nádory děložního čípku * virologie   MeSH
• onkogenní proteiny virové * genetika   MeSH
• Papillomavirus E7 - proteiny * genetika   MeSH
• progrese nemoci MeSH
• RNA virová genetika   MeSH
• techniky amplifikace nukleových kyselin metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Human papillomavirus (HPV) causes adult-onset recurrent respiratory papillomatosis (AORRP), but AORPP prevalence is much lower than HPV prevalence. Thus, HPV infection is necessary, but not sufficient, to cause AORRP and other factors likely contribute to its pathogenesis. The present study aimed to investigate whether co-infection with herpetic viruses may contribute to the pathogenesis of AORRP. DESIGN: Prospective case-control study conducted from January 2018 to November 2019. SETTINGS: Tertiary referral centre. PARTICIPANTS: Eighteen consecutive patients with AORRP and 18 adults with healthy laryngeal mucosa (control group) undergoing surgery. MAIN OUTCOME MEASURES: Cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex viruses 1 and 2, human herpesvirus 6, varicella zoster virus and HPV (including genotyping) were detected in biopsies of papilloma or healthy mucosa using real-time polymerase chain reaction and reverse line blot. Dysplasia and Ki67 levels were determined in papilloma specimens. RESULTS: EBV was present in 6 (33.3%) AORRP patients and no control patients (P = .019). Presence was not dependent on tobacco exposure (P = .413) or HPV genotype or concentration (P > .999). EBV presence was strongly related to increased cell proliferation (P = .005) and number of previous surgeries (P = .039), but not dysplasia (P > .999). Human herpesvirus 6 was found in 3 (16.7%) AORRP biopsies, with one false positive. No other herpetic virus was found. CONCLUSIONS: Unlike other herpetic viruses, EBV seems to interact with HPV, enhancing cell proliferation and contributing to the pathogenesis and progression of AORRP. Further research is required to elucidate specific interactions and their role in the pathogenesis of AORRP.

• MeSH
• biopsie MeSH
• infekce dýchací soustavy virologie   MeSH
• infekce papilomavirem virologie   MeSH
• laryngoskopie MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• recidiva MeSH
• rizikové faktory MeSH
• senzitivita a specificita MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: The effect of SAM vaginal gel, a medical device containing adsorptive silicon dioxide and antioxidative sodium selenite and citric acid, on histologically-proven cervical intraepithelial neoplasia type 2 (CIN2) as well as p16 positive CIN1, and on the presence of the onco-marker p16 was investigated. METHODS: 216 women aged 25-60 years were randomized to either receive an intravaginal daily dose of SAM gel for three 28-day periods, or be followed-up without intervention. The primary endpoint was efficacy, defined as a combined histological and cytological regression. At baseline and after 3 months participants had: a guided biopsy including p16 immunohistochemical (IHC) staining, only if a lesion was visible at colposcopy; a cervical smear for cytology, high-risk human papillomavirus (hr-HPV) and a p16/Ki-67 test. At 6 months a further cytology and p16/Ki-67 test was performed. RESULTS: Regression of CIN lesions was observed in 78 out of 108 patients (72.2%) in the SAM gel arm and in 27 out of 108 patients (25.0%) in the control arm. Similarly, the change in the p16/Ki-67 cytological test status was significantly in favor of the treatment arm. The prevalence of hr-HPV decreased significantly (p < 0.001) in the treatment arm, from 87.0% to 39.8%, while it slightly increased in the control arm, from 78.7% to 83.3%. At 6 months the cytological regression in the treatment group and the highly significant effect on p16/Ki-67 was still present. CONCLUSION: SAM vaginal gel enhances the regression of cervical lesions and clears hr-HPV and p16/Ki-67 in smears significantly, thus offering an active non-destructive management to prevent cervical cancer. TRIAL REGISTRATION NUMBER: ISRCTN11009040, date of registration: 10/12/2019; https://doi.org/10.1186/ISRCTN11009040 ; retrospectively registered.

• MeSH
• antigen Ki-67 účinky léků   MeSH
• antioxidancia aplikace a dávkování   MeSH
• aplikace intravaginální MeSH
• cytodiagnostika MeSH
• dospělí MeSH
• dysplazie děložního hrdla patologie   terapie   MeSH
• geny p16 MeSH
• infekce papilomavirem terapie   virologie   MeSH
• inhibitor p16 cyklin-dependentní kinasy účinky léků   MeSH
• kolposkopie MeSH
• kyselina citronová aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory děložního čípku prevence a kontrola   MeSH
• oxid křemičitý aplikace a dávkování   MeSH
• seleničitan sodný aplikace a dávkování   MeSH
• těhotenství MeSH
• vaginální krémy, pěny a želé * MeSH
• vaginální stěr MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.

• MeSH
• celogenomová asociační studie MeSH
• exprese genu MeSH
• genetická predispozice k nemoci MeSH
• haplotypy MeSH
• HLA antigeny klasifikace   genetika   imunologie   MeSH
• humorální imunita * MeSH
• infekce papilomavirem genetika   imunologie   patologie   virologie   MeSH
• kouření patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 imunologie   patogenita   MeSH
• lokus kvantitativního znaku MeSH
• metaanalýza jako téma MeSH
• nádory orofaryngu genetika   imunologie   patologie   virologie   MeSH
• nádory úst genetika   imunologie   patologie   virologie   MeSH
• onkogenní proteiny virové genetika   imunologie   MeSH
• protilátky virové biosyntéza   MeSH
• represorové proteiny genetika   imunologie   MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• virové plášťové proteiny genetika   imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: Anal cancer (AC) screening is justified in high-risk populations, particularly HIV-positive men having sex with men (MSM). HR-HPV testing could improve the efficiency of cytologically based screening of AC, as in the screening of biologically analogical cervical cancer. The specificity of HR-HPV testing is influenced by the prevalence of HR-HPV infection in the screened population. Reported anal HR-HPV DNA prevalence in MSM is high, but HR-HPV mRNA reflects rather long-term infections and is more specific for high-grade lesions. However, no data were published about HR-HPV DNA and mRNA prevalence in the Czech AC screening population. METHOD: Results of liquid-based anal cytology of 203 predominantly HIV-positive MSM from the Czech AC screening cohort were correlated with results of DNA and E6/E7 mRNA testing of 14 HR-HPV types, and HPV16 genotyping. Eighty-one MSM underwent a standard anoscopy. RESULTS: A total of 109 (53.7%) samples had abnormal cytology, with 12 (5.9%) ASC-H/HSIL, 67 (33.0%) samples cytologically negative, and 27 (13.3%) unsatisfactory. HR-HPV DNA was detected in 134 (66.0%) and HR-HPV RNA in 72 (35.5%) anal smears. HR-HPV mRNA and HPV16 mRNA positivity were associated with abnormal cytology (p = .0037, p = .0021). No significant association was found between HR-HPV DNA or HPV16 DNA positivity and abnormal cytology. No high-grade lesions were revealed by anoscopy. CONCLUSION: Prevalence of anal HR-HPV DNA among Czech MSM is high, however, the prevalence of HR-HPV mRNA is half and associated with abnormal cytology. Our results indicate an increased efficiency of cytological screening when combined with HR-HPV mRNA testing.

• MeSH
• časná detekce nádoru statistika a číselné údaje   MeSH
• DNA virů genetika   MeSH
• dospělí MeSH
• homosexualita mužská genetika   statistika a číselné údaje   MeSH
• infekce papilomavirem epidemiologie   patologie   virologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• mladý dospělý MeSH
• nádory anu genetika   patologie   MeSH
• prevalence MeSH
• sexuální a genderové menšiny statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Plasmacytoid dendritic cells (pDCs) are the most potent type I interferon-producing cells and play an important role in antiviral immunity. Tumor-infiltrating pDCs were shown to be predominantly pro-tumorigenic, with reduced ability to produce interferon alpha (IFNα) and confirmed capacity to prime regulatory T cells (Tregs) by the ICOS/ICOS-L pathway. Because a significant number of HNSCCs are induced by human papillomaviruses and show markedly different immune profiles than non-virally induced tumors, we compared the phenotype and functional capacity of HNSCC-infiltrating pDCs to the HPV status of the tumor. We observed a reduced capacity of pDCs to produce IFNα upon toll-like receptor activation in HPV-negative samples and a rather uncompromised functionality in HPV-associated tumors. Additionally, supernatants from non-virally induced but not HPV-associated tumor cell suspensions significantly inhibited IFNα production by peripheral blood-derived pDCs. We identified IL-10 and TNFα as the soluble pDC-suppressive factors with the highest variability between HPV-negative and HPV-positive tumor-derived supernatants. Additionally, we observed a positive correlation of tumor-infiltrating pDCs with Tregs in HPV-negative samples but not in virally induced tumors. Overall, our study indicates that the immunosuppressive cytokine milieu rich in IL-10 and TNFα in HPV-negative but not in HPV-positive HNSCC significantly affects the functional capacity of tumor-infiltrating pDCs, and such dysfunctional pDCs may further support the immunosuppressive tumor microenvironment by promoting the expansion of Tregs in the tumor tissue.

• MeSH
• biologické markery MeSH
• cytokiny metabolismus   MeSH
• dendritické buňky imunologie   metabolismus   patologie   MeSH
• dlaždicobuněčné karcinomy hlavy a krku etiologie   metabolismus   patologie   MeSH
• exprese genu MeSH
• infekce papilomavirem komplikace   virologie   MeSH
• interferon alfa imunologie   metabolismus   MeSH
• lidé MeSH
• náchylnost k nemoci MeSH
• nádorové mikroprostředí * imunologie   MeSH
• regulační T-lymfocyty imunologie   metabolismus   MeSH
• studie případů a kontrol MeSH
• T-lymfocyty - podskupiny imunologie   metabolismus   MeSH
• virová transformace buněk MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Background/Aim: The incidence of oropharyngeal tumours induced by human papillomaviruses (HPV) is ever increasing. Information about oral HPV prevalence and its risk factors are very important for future screening and early diagnosis of the disease. The present study aimed to assess oral HPV prevalence in healthy population and risk factors for HPV infection, since this data is scarce or even missing in Central Europe. Patients and Methods: HPV prevalence in oral rinse and HPV-specific antibodies in peripheral blood were investigated in two groups of healthy participants. Group I consisted of 294 students who reached sexual maturity after the HPV vaccine had been licensed with mean age 23.2 years, and Group II of 215 unvaccinated participants with the mean age 55.7 years. Additionally, the risk factors were evaluated. Results: In Group I, 2% of participants were positive for oral HPV DNA. A statistically significantly higher rate (8.8%) was found in Group II. The seropositivity rates for anamnestic HPV antibodies were comparable in both groups. None of the analysed risk factors was significantly associated with oral HPV positivity. Conclusion: The lower prevalence of oral HPV DNA in younger participants suggests the positive influence of vaccination against oral HPV.

• MeSH
• dospělí MeSH
• infekce papilomavirem epidemiologie   virologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• patologie ústní dutiny MeSH
• prevalence MeSH
• rizikové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH