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1.
Ann Agric Environ Med ; 27(3): 379-383, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32955218

RESUMO

INTRODUCTION: Cervical cancer is the fourth neoplasm in women with respect to incidence. In Poland, both cervical cancer incidence and corresponding mortality are gradually decreasing. Despite these improvements, the epidemiological situation significantly deviates from European standards. Poland has one of Europe's lowest five-year survival rates at 54.1% for patients diagnosed in 2000-2002, compared to the European mean value of 62.1%. OBJECTIVE: The aim of this study is to present health policy programmes related to HPV vaccinations run by local self-government units in 2009-2016. MATERIAL AND METHODS: The research is based on analysis of already existing data developed by provincial governors and annual information reviews on health-policy programmes implemented by local self-government units presented to the Ministry of Health. All the programmes that included HPV vaccinations have been subjected to analysis. RESULTS: In 2009-2016, local government units implemented a total of 1,204 health policy programmes that covered HPV vaccinations. Under these programmes, 2.05% of girls aged 10-14 were vaccinated. Percentage-wise, these were communes that contributed the most financially to the HPV vaccination programmes, whereas the counties the least. CONCLUSIONS: Local self-government's programmes covering HPV vaccinations conform with the trends outlined in strategic documents on fighting neoplastic diseases. It is possible that the availability of HPV vaccination was limited for girls living in rural communes. Differences in the number of programmes, number of vaccinated girls and the financial outlays allocated for the implementation of HPV vaccination programmes in particular provinces, may be determined by the epidemiological situation in a given region, measured by the incidence rate of cervical cancer.


Assuntos
Política de Saúde , Governo Local , Papillomaviridae/imunologia , Infecções por Papillomavirus/terapia , Vacinas contra Papillomavirus/administração & dosagem , Vacinação/legislação & jurisprudência , Adolescente , Criança , Feminino , Humanos , Polônia
2.
MMWR Morb Mortal Wkly Rep ; 69(37): 1283-1287, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32941412

RESUMO

Human papillomavirus (HPV) causes most cervical cancers and some cancers of the penis, vulva, vagina, oropharynx, and anus. Cervical precancers can be detected through screening. HPV vaccination with the 9-valent HPV vaccine (9vHPV) can prevent approximately 92% of HPV-attributable cancers (1).* Previous studies have shown lower incidence of HPV-associated cancers in non-Hispanic American Indian and Alaska Native (AI/AN) populations compared with other racial subgroups (2); however, these rates might have been underestimated as a result of racial misclassification. Previous studies have shown that cancer registry data corrected for racial misclassification resulted in more accurate cancer incidence estimates for AI/AN populations (3,4). In addition, regional variations in cancer incidence among AI/AN populations suggest that nationally aggregated data might not adequately describe cancer outcomes within these populations (5). These variations might, in part, result from geographic disparities in the use of health services, such as cancer screening or vaccination (6). CDC analyzed data for 2013-2017 from central cancer registries linked with the Indian Health Service (IHS) patient registration database to assess the incidence of HPV-associated cancers and to estimate the number of cancers caused by HPV among AI/AN populations overall and by region. During 2013-2017, an estimated 1,030 HPV-associated cancers were reported in AI/AN populations. Of these cancers, 740 (72%) were determined to be attributable to HPV types targeted by 9vHPV; the majority were cervical cancers in females and oropharyngeal cancers in males. These data can help identify regions where AI/AN populations have disproportionately high rates of HPV-associated cancers and inform targeted regional vaccination and screening programs in AI/AN communities.


Assuntos
Nativos do Alasca/estatística & dados numéricos , Índios Norte-Americanos/estatística & dados numéricos , Neoplasias/etnologia , Neoplasias/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/etnologia , Feminino , Humanos , Incidência , Masculino , Sistema de Registros , Estados Unidos/epidemiologia
3.
Anticancer Res ; 40(10): 5621-5630, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988886

RESUMO

BACKGROUND: Targeted therapies in the treatment of head and neck squamous cell carcinoma (HNSCC) are subject to extensive research. Different mutations of genes belonging to the fibroblast growth factor (FGF) family have been detected in HNSCC. In this study, we examined the expression of FGF1 and FGF2 after treatment with small-molecule tyrosine kinase inhibitors (TKIs) and an inhibitor of mechanistic target of rapamycin (mTOR) in vitro using human papillomavirus (HPV)-positive and -negative SCC lines. MATERIALS AND METHODS: Cells of two human HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with 20 µmol/l of erlotinib, gefitinib, nilotinib, dasatinib, or everolimus for 24-96 h. Cell proliferation was assessed by proliferation assay and the protein concentrations of FGF1 and FGF2 by sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those for untreated HPV-negative SCC cells. RESULTS: FGF1 and FGF2 were detected in all three tested cell lines. The tested TKIs significantly (p<0.05 reduced) FGF1 expression in the UMSCC-11A cell line within the first 24 h. At later time points, the tested TKIs and everolimus significantly (p<0.05) increased FGF1 and FGF2 expression in HPV-negative and -positive cancer cell lines. The effect was stronger in the HPV-positive cell line. CONCLUSION: Alterations in FGF signalling are considered to be relevant drivers of tumourigenesis in some HNSCCs. Our results show that the expression of FGF1 and -2 can be influenced effectively by small-molecule TKIs and everolimus. Based on our data, future research should include combinations of specific FGF inhibitors, mTOR inhibitors and other TKIs in the treatment of HNSCC and research on FGF-mediated drug escape mechanisms.


Assuntos
Everolimo/farmacologia , Fatores de Crescimento de Fibroblastos/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Serina-Treonina Quinases TOR/genética , Linhagem Celular Tumoral , Dasatinibe/farmacologia , Cloridrato de Erlotinib/farmacologia , Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Gefitinibe/farmacologia , Papillomavirus Humano 16/efeitos dos fármacos , Papillomavirus Humano 16/patogenicidade , Humanos , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/patogenicidade , Inibidores de Proteínas Quinases/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Serina-Treonina Quinases TOR/antagonistas & inibidores
4.
J Exp Clin Cancer Res ; 39(1): 200, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967703

RESUMO

BACKGROUND: SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas. METHODS: The study has been conducted using the TCGA and the Regina Elena Institute databases and validated by experimental model in HNSCC cells. We also included data from one COVID19 patient who went under surgery for HNSCC. RESULTS: TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. It was more evident in women than in men, in TP53 mutated versus wild TP53 tumors, in HPV negative patients compared to HPV positive counterparts. Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. All variables had a statistically significant independent effect on TMPRSS2. In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPRSS2 promoter methylation. CONCLUSIONS: Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Neoplasias de Cabeça e Pescoço/patologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Pneumonia Viral/complicações , Serina Endopeptidases/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estudos de Casos e Controles , Infecções por Coronavirus/virologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pandemias , Infecções por Papillomavirus/virologia , Pneumonia Viral/virologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Taxa de Sobrevida
5.
Medicine (Baltimore) ; 99(38): e22320, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957398

RESUMO

Cervical cancer is a serious global health problem. The objective of this study was to provide a suitable cytology-based cervical screening method in women of different ages in primary hospitals.This study was a retrospective cohort study that included 9765 women who underwent primary cytology-based cervical screening and were grouped by age (35-44, 45-54, and 55-64 years old). Patients with abnormal cytology on the primary cervical thin-prep cytologic test (TCT) were advised to undergo triage human papillomavirus (HPV) test. Furthermore, patients with positive outcomes of the 2 indices underwent cervical tissue biopsy. The positive rate of TCT and HPV was compared among the 3 defined age groups. The sensitivity, specificity, and positive predictive value of TCT and HPV were assessed.In total, 2.5% (241/9765) of women had atypical squamous cells of undetermined significance or worse by TCT. High-risk (HR)-HPV infection was found in 70 triage participants. Neoplastic changes were confirmed in 95 patients (95/437, 21.7%) by biopsies. Among the different age groups, the positive rate of abnormal cytology was significantly different (P = .003), and the positive rate of HR-HPV was similar (P = .299). The sensitivity of initial TCT testing to detect intraepithelial neoplasia was higher than that of triage HPV testing, whereas the specificity, the positive predictive value of triage HPV testing was higher than that of TCT. The Youden index of HPV testing was higher than that of TCT detection in the 3 age groups, namely 0.582 versus 0.432, 0.553 versus 0.228, and 0.416 versus 0.332, respectively.The results of this study indicate that TCT testing is suitable as a cervical cancer screening method for women ≥35 years old in primary hospitals. Triage testing for women with HR-HPV has a high negative predictive value, reduces the rate of misdiagnosis, seems to be an excellent triage method for repeat atypical squamous cells of undetermined significance, and reduces the number of referral colposcopies preventing unnecessary overtreatment. The results of this study provide a crucial foundation for a unified guideline cervical cancer screening for primary health care institutions.


Assuntos
Detecção Precoce de Câncer/métodos , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Distribuição por Idade , China , Feminino , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Neoplasias do Colo do Útero/virologia
6.
Adv Exp Med Biol ; 1268: 195-209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918220

RESUMO

Human papillomaviruses (HPVs) infect squamous epithelia and can induce hyperproliferative lesions. More than 220 different HPV types have been characterized and classified into five different genera. While mucosal high-risk HPVs have a well-established causal role in anogenital carcinogenesis, the biology of cutaneous HPVs is less well understood.From patients with the rare genetic disorder epidermodysplasia verruciformis (EV) and animal models, evidence is accumulating that cutaneous PV of genus ß synergize with ultraviolet (UV) radiation in the development of cutaneous squamous cell carcinoma (cSCC). In 2009, the International Agency for Research on Cancer (IARC) classified the genus ß-HPV types 5 and 8 as "possible carcinogenic" biological agents (group 2B) in EV disease. Epidemiological and biological studies indicate that genus ß-PV infection may also play a role in UV-mediated skin carcinogenesis in non-EV patients. However, they rather act at early stages of carcinogenesis and become dispensable for the maintenance of the malignant phenotype, compatible with a "hit-and-run" mechanism.This chapter will give an overview on genus ß-PV infections and discuss similarities and differences of cutaneous and genus α mucosal high-risk HPV in epithelial carcinogenesis.


Assuntos
Papillomaviridae/patogenicidade , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/virologia , Animais , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/virologia , Epidermodisplasia Verruciforme/etiologia , Epidermodisplasia Verruciforme/virologia , Humanos , Raios Ultravioleta/efeitos adversos
8.
PLoS Pathog ; 16(9): e1008827, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32886721

RESUMO

Global burden of cervical cancer, the most common cause of mortality caused by human papillomavirus (HPV), is expected to increase during the next decade, mainly because current alternatives for HPV vaccination and cervical cancer screening programs are costly to be established in low-and-middle income countries. Recently, we described the development of the broadly protective, thermostable vaccine antigen Trx-8mer-OVX313 based on the insertion of eight different minor capsid protein L2 neutralization epitopes into a thioredoxin scaffold from the hyperthermophilic archaeon Pyrococcus furiosus and conversion of the resulting antigen into a nanoparticle format (median radius ~9 nm) upon fusion with the heptamerizing OVX313 module. Here we evaluated whether the engineered thioredoxin scaffold, in addition to humoral immune responses, can induce CD8+ T-cell responses upon incorporation of MHC-I-restricted epitopes. By systematically examining the contribution of individual antigen modules, we demonstrated that B-cell and T-cell epitopes can be combined into a single antigen construct without compromising either immunogenicity. While CD8+ T-cell epitopes had no influence on B-cell responses, the L2 polytope (8mer) and OVX313-mediated heptamerization of the final antigen significantly increased CD8+ T-cell responses. In a proof-of-concept experiment, we found that vaccinated mice remained tumor-free even after two consecutive tumor challenges, while unvaccinated mice developed tumors. A cost-effective, broadly protective vaccine with both prophylactic and therapeutic properties represents a promising option to overcome the challenges associated with prevention and treatment of HPV-caused diseases.


Assuntos
Antígenos de Neoplasias , Antígenos Virais , Proteínas Arqueais , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer , Imunidade Celular/efeitos dos fármacos , Nanopartículas , Papillomaviridae , Vacinas contra Papillomavirus , Pyrococcus furiosus/química , Tiorredoxinas , Neoplasias do Colo do Útero/imunologia , Animais , Antígenos de Neoplasias/química , Antígenos de Neoplasias/farmacologia , Antígenos Virais/química , Antígenos Virais/farmacologia , Proteínas Arqueais/química , Proteínas Arqueais/farmacologia , Linfócitos T CD8-Positivos/patologia , Vacinas Anticâncer/química , Vacinas Anticâncer/farmacologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/farmacologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/farmacologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/uso terapêutico , Papillomaviridae/química , Papillomaviridae/imunologia , Vacinas contra Papillomavirus/química , Vacinas contra Papillomavirus/farmacologia , Tiorredoxinas/química , Tiorredoxinas/farmacologia , Neoplasias do Colo do Útero/virologia
9.
Zhonghua Bing Li Xue Za Zhi ; 49(8): 812-815, 2020 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-32746548

RESUMO

Objective: To investigate the use of p16(INK4a) immuno-stained cytology as the primary screening for cervical cancer prevention. Methods: From March to August 2018, 902 women from Shenzhen and surrounding area were recruited for cervical cancer screening with ThinPrep Cytologic Test (TCT), cobas4800 HPV test, and p16(INK4a) co-test. Colpo/biopsies were performed using the point of interest biopsy protocol of directed and random cervical biopsies plus endocervical curettage for all women, any of whose tests was positive. Two senior cytopathologists interpreted TCT and p16(INK4a) test. The performance of p16(INK4a) for early detection of CIN2+ and inter-observer reproducibility of the interpretation of p16(INK4a) were evaluated. Results: The positive rates of HPV test, p16(INK4a) co-test and TCT diagnosed as LSIL/AGC or higher grade were 8.1% (73/902), 6.8% (61/902) and 4.7% (42/902), respectively. Colposcopy referring rate was 79.6% (109/137), among which 10 cases were diagnosed as CIN2+ (5 cases of CIN2 and 5 cases of CIN3). The sensitivity and specificity for CIN2+ of p16(INK4a) test, TCT (LSIL/AGC or higher grade) and HPV test were 90.0%, 80.0%, 100.0% and 90.9%, 91.9%, 82.5%, respectively. Compared to TCT and HPV test, there was no significant difference in sensitivity and specificity between p16(INK4a) and TCT/HPV test (P>0.05). The Kappa value of the 2 cytopathologists in interpreting p16(INK4a) and TCT was 0.944 and 0.425, respectively (P<0.05). Conclusions: p16(INK4a) for cervical cancer screening is equally sensitive to HPV test and specific to TCT while subjective difference of cytopathologists' interpretation of p16(INK4a) is small. Therefore, p16(INK4a) can be used as a new cervical cancer screen method for its better diagnostic performance.


Assuntos
Neoplasia Intraepitelial Cervical , Papillomaviridae , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Inibidor p16 de Quinase Dependente de Ciclina , Detecção Precoce de Câncer , Feminino , Humanos , Gravidez , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
PLoS Pathog ; 16(8): e1008792, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32813746

RESUMO

Tumor suppressors can exert pro-proliferation functions in specific contexts. In the beta human papillomavirus type 38 (HPV38) experimental model, the viral proteins E6 and E7 promote accumulation of a wild-type (WT) p53 form in human keratinocytes (HKs), promoting cellular proliferation. Inactivation of p53 by different means strongly decreases the proliferation of HPV38 E6/E7 HKs. This p53 form is phosphorylated at S392 by the double-stranded RNA-dependent protein kinase PKR, which is highly activated by HPV38. PKR-mediated S392 p53 phosphorylation promotes the formation of a p53/DNMT1 complex, which inhibits expression of integrin alpha 1 (ITGA1), a repressor of epidermal growth factor receptor (EGFR) signaling. Ectopic expression of ITGA1 in HPV38 E6/E7 HKs promotes EGFR degradation, inhibition of cellular proliferation, and cellular death. Itga1 expression was also inhibited in the skin of HPV38 transgenic mice that have an elevated susceptibility to UV-induced skin carcinogenesis. In summary, these findings reveal the existence of a specific WT p53 form that displays pro-proliferation properties.


Assuntos
Proteínas de Transporte/antagonistas & inibidores , Proliferação de Células , Queratinócitos/patologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/complicações , Proteínas Repressoras/metabolismo , Neoplasias Cutâneas/etiologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Células Cultivadas , Regulação para Baixo , Humanos , Queratinócitos/imunologia , Queratinócitos/virologia , Camundongos , Camundongos Transgênicos , Proteínas Oncogênicas Virais/genética , Papillomaviridae/isolamento & purificação , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/virologia , Proteínas Repressoras/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Proteína Supressora de Tumor p53/genética
11.
Life Sci ; 258: 118236, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32795537

RESUMO

Cancer cells exhibit distinct energy metabolic pathways due to multiple oncogenic events. In normoxia condition, the anaerobic glycolysis (Warburg effect) is highly observed in head and neck squamous cell carcinoma (HNSCC). HNSCC is associated with smoking, chewing tobacco, consumption of alcohol or Human Papillomavirus (HPV) infection primarily HPV16. In recent years, the correlation of HPV with HNSCC has significantly expanded. Despite the recent advancement in therapeutic approaches, the rate of HPV infected HNSCC has significantly increased in the last few years, specifically, in lower middle-income countries. The oncoproteins of High-risk Human Papillomavirus (HR-HPV), E6 and E7, alter the metabolic phenotype in HNSCC, which is distinct from non-HPV associated HNSCC. These oncoproteins, modulate the cell cycle and metabolic signalling through interacting with tumor suppressor proteins, p53 and pRb. Since, metabolic alteration represents a major hallmark for tumorigenesis, HPV acts as a source of biomarker linked to cancer progression in HNSCC. The dependency of cancer cells to specific nutrients and alteration of various metabolic associated genes may provide a unique opportunity for pharmacological intervention in HPV infected HNSCC. In this review, we have discussed the molecular mechanism (s) and metabolic regulation in HNSCC depending on the HPV status. We have also discussed the possible potential therapeutic approaches for HPV associated HNSCC through targeting metabolic pathways.


Assuntos
Metabolismo Energético/fisiologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/virologia , Papillomaviridae/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Glicólise/fisiologia , Humanos
12.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 55(8): 571-577, 2020 Aug 09.
Artigo em Chinês | MEDLINE | ID: mdl-32842349

RESUMO

Objective: To explore differentially expressed genes (DEG) and pathways between human papilloma virus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC) and to search gene targets for diagnosis and treatment of HPV-related HNSCC. Methods: HPV-related HNSCC expression profile chips of GSE3292 (including 8 HPV-positive and 28 HPV-negative HNSCC tissues, of which 15 collected from oral cavity cancer, 9 from oropharyngeal cancer, 9 from laryngeal cancer and 3 from hypopharyngeal cancer) were selected from Gene Expression Omnibus (GEO) database of National Center for Biotechnology Information and DEG were screened out using Gene-Cloud of Biotechnology Informs (GCBI). Gene ontology and pathway enrichment analysis were performed using DAVID and protein-to-protein interaction (PPI) network was constructed by STRING. Hub genes were identified by Cytoscape and then performed pathway enrichment analysis. Finally, expression differences of hub genes in the cancer genome atlas (TCGA) database were checked using UALCAN. Results: Five hundred and seventy-three DEG were screened out from more than 25 000 genes detected in the chips including 539 up-regulated genes and 34 down regulated ones. Twenty-seven hub genes including cyclin-dependent kinases 1(CDK1), proliferating cell nuclear antigen (PCNA), minichromosome maintenance proteins (MCM) family (MCM2, MCM3, MCM6 and MCM7), replication factor C subunit 4 (RFC4) and kinesin family member 11 (KIF11) were identified after two rounds of Cytoscape screening. Gene ontology and pathway analysis showed that DEG were mainly distributed in chromosome, nucleoplasm, nuclear lumen and membrane-enclosed lumen and participated in biological processes such as DNA replication, DNA metabolism, cell cycle and cell division, and also 6 major signaling pathways centered on p53 signaling pathway (P<0.01). All hub genes were expressed differently between HPV-positive and negative HNSCC in TCGA database(P<0.01). Conclusions: Hub genes including CDK1, PCNA, MCM family (MCM2, MCM3, MCM6 and MCM7) act as an important part on HPV-induced HNSCC and the p53 pathway is the key of this process and plays different regulatory roles between two subtypes of HNSCC. CDK1, MCM7 and RFC4 are expected to be potential treatment targets for HPV-positive HNSCC while MCM2, MCM3, PCNA and KIF11 may be employed as biomarkers for diagnosis and prognosis.


Assuntos
Neoplasias de Cabeça e Pescoço , Papillomaviridae/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Transdução de Sinais
13.
PLoS One ; 15(8): e0237455, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32777809

RESUMO

De novo assembly of sequence reads from next generation sequencing platforms is a common strategy for detecting presence and sequencing of viruses in biospecimens. Amplification artifacts and presence of several related viruses in the same specimen can lead to assembly of erroneous, chimeric sequences. We now report that such chimeras can also occur between viral and non-viral biological sequences incorrectly joined together which may cause erroneous detection of viruses, highlighting the importance of performing a chimera checking step in bioinformatics pipelines. Using Illumina NextSeq and metagenomic sequencing, we analyzed 80 consecutive non-melanoma skin cancers (NMSCs) from 11 immunosuppressed patients together with 11 NMSCs from patients who had only developed 1 NMSC. We aligned high-quality reads against a Human Papillomavirus (HPV) database and found HPV sequences in 9/91 specimens. A previous bioinformatic analysis of the same crude sequencing data from some of these samples had found an additional 3 specimens to be HPV-positive after performing de novo assembly. The reason for the discrepancy was investigated and found to be mostly caused by chimeric sequences containing both viral and non-viral sequences. Non-viral sequences were present in these 3 samples. To avoid erroneous detection of HPV when performing sequencing, we thus developed a novel script to identify HPV chimeric sequences.


Assuntos
Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Hibridização Genética , Algoritmos , Metagenômica , Papillomaviridae/genética
14.
BMC Infect Dis ; 20(1): 629, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32842982

RESUMO

BACKGROUND: In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts. METHODS: The vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n = 78), women with low-grade squamous intraepithelial lesions (LSIL, n = 51), women with high-grade squamous intraepithelial lesions (HSIL, n = 23), women with invasive cervical cancer (Cancer, n = 9) and healthy women without HPV infection (Normal, n = 68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3-4) using Illumina MiSeq. RESULTS: HPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus, Gardnerella and Atopobium. Accordingly, HPV infection increased the relative abundance of Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus. The increased proportions of Bacillus, Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera. The most abundant bacterium in the LSIL group was Prevotella amnii. However, Prevotella timonensis, Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus, Sneathia, Acidovorax, Oceanobacillus profundus, Fusobacterium, Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis. Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs. CONCLUSIONS: This work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.


Assuntos
Biodiversidade , Neoplasia Intraepitelial Cervical/epidemiologia , Progressão da Doença , Microbiota/genética , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Vagina/microbiologia , Adulto , Idoso , Neoplasia Intraepitelial Cervical/virologia , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Lactobacillus/genética , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , RNA Ribossômico 16S/genética , Neoplasias do Colo do Útero/virologia
15.
PLoS Pathog ; 16(8): e1008718, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32797103

RESUMO

APOBEC3 enzymes are innate immune effectors that introduce mutations into viral genomes. These enzymes are cytidine deaminases which transform cytosine into uracil. They preferentially mutate cytidine preceded by thymidine making the 5'TC motif their favored target. Viruses have evolved different strategies to evade APOBEC3 restriction. Certain viruses actively encode viral proteins antagonizing the APOBEC3s, others passively face the APOBEC3 selection pressure thanks to a depleted genome for APOBEC3-targeted motifs. Hence, the APOBEC3s left on the genome of certain viruses an evolutionary footprint. The aim of our study is the identification of these viruses having a genome shaped by the APOBEC3s. We analyzed the genome of 33,400 human viruses for the depletion of APOBEC3-favored motifs. We demonstrate that the APOBEC3 selection pressure impacts at least 22% of all currently annotated human viral species. The papillomaviridae and polyomaviridae are the most intensively footprinted families; evidencing a selection pressure acting genome-wide and on both strands. Members of the parvoviridae family are differentially targeted in term of both magnitude and localization of the footprint. Interestingly, a massive APOBEC3 footprint is present on both strands of the B19 erythroparvovirus; making this viral genome one of the most cleaned sequences for APOBEC3-favored motifs. We also identified the endemic coronaviridae as significantly footprinted. Interestingly, no such footprint has been detected on the zoonotic MERS-CoV, SARS-CoV-1 and SARS-CoV-2 coronaviruses. In addition to viruses that are footprinted genome-wide, certain viruses are footprinted only on very short sections of their genome. That is the case for the gamma-herpesviridae and adenoviridae where the footprint is localized on the lytic origins of replication. A mild footprint can also be detected on the negative strand of the reverse transcribing HIV-1, HIV-2, HTLV-1 and HBV viruses. Together, our data illustrate the extent of the APOBEC3 selection pressure on the human viruses and identify new putatively APOBEC3-targeted viruses.


Assuntos
Citidina Desaminase/metabolismo , Genoma Viral/genética , Interações Hospedeiro-Patógeno/genética , Seleção Genética/genética , Replicação Viral/genética , Coronaviridae/genética , Humanos , Imunidade Inata/imunologia , Papillomaviridae/genética , Parvoviridae/genética , Polyomaviridae/genética , Proteínas Virais/genética
16.
Rev Chilena Infectol ; 37(2): 111-116, 2020 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-32730475

RESUMO

BACKGROUND: Human papilloma virus (HPV) is one of the most frequent sexually transmitted infections, especially among young people. AIMS: To describe the prevalence of genital HPV infections, to identify clinical-epidemiological factors associated with them and to determine the frequency of viral strains. METHODS: Endocervical samples were studied of 505 women between 15 and 49 years old, who attended the laboratory of the Institute of Social Security, residents of Posadas, Misiones, for the study of vaginal exudate, between January 2012 and June 2013. A 450-base pair fragment within the HPV L1 region was amplified. Genotype detection was performed through the study of the restriction fragment length polymorphism (RFLP). RESULTS: The prevalence of total HPV carriage was 30.7%, and of these 71.6% corresponded to high risk (mainly HPV 16 [35.1%], 58 [10.8%] and 31 [8.1%]). HPV detection was higher in women aged 15 to 24 years (OR: 1.48, 95% CI: 1.01-2.18) and with more sexual partners (OR: 1.81, 95% CI: 1, 02-3.22). There was no association with pregnancy, stability of the couple, contraceptive methods, age at onset of sexual intercourse, or smoking. CONCLUSIONS: The identification and typing of HPV in this study provides information regarding the high prevalence of HPV and the substantial proportion of cases with oncogenic genotypes among sexually active women in this region of Argentina.


Assuntos
Seguro Saúde , Adolescente , Adulto , Argentina , DNA Viral , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae , Infecções por Papillomavirus , Gravidez , Prevalência , Fatores de Risco , Adulto Jovem
17.
Rev Col Bras Cir ; 47: e20202543, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32638910

RESUMO

AIM: to evaluate the presence of subclinical HPV-induced anal lesions with anal cytology, High-Resolution Anoscopy (HRA) and HPV genotyping by polymerase chain reaction (PCR) in the follow-up of treated condylomata acuminata (CA). METHODS: seventy-nine male patients were included. One month after anal CA eradication, the patients underwent brush samples collection for anal cytology and PCR, and HRA with biopsy of acetowhite lesions. These methods were compared within all patients and between groups, according to Human Immunodeficiency Virus (HIV) infection status: HIV-negative; HIV-positive with TCD4 count above and below 350 cells/mm3. RESULTS: the most frequent HPV types were 6 and 16. HPV DNA was isolated in 92%. HIV infection was associated with a higher number of oncogenic HPV types (p=0.038). All patients with negative PCR had negative HRA and cytology. There were no differences in cytological, HRA or histopathological findings between groups. CONCLUSION: the association of the findings of cytopathology, HRA and genotyping of HPV refined the diagnosis of HPV-induced lesions. The degree of immunodeficiency was not associated with increase in remnant HPV-induced anal lesions.


Assuntos
Neoplasias do Ânus , Condiloma Acuminado , Papillomaviridae/genética , Infecções por Papillomavirus , Canal Anal , DNA , Seguimentos , Genótipo , Infecções por HIV , Humanos , Masculino , Reação em Cadeia da Polimerase
20.
J Am Dent Assoc ; 151(8): 560-567, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32718485

RESUMO

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection and is responsible for most anogenital and oropharyngeal cancers. Dental care providers can be advocates for vaccine uptake, yet little is known about patients' perceptions of the role of dental care providers in HPV education and prevention. METHODS: Parents of adolescents aged 9 through 17 years were recruited from the Minnesota State Fair to survey their awareness and knowledge of the HPV vaccine. Parents were also surveyed about their attitudes toward and comfort in receiving HPV vaccination recommendations and counseling from oral health care providers. RESULTS: The authors interviewed 208 parents, most of whom felt that dentists were qualified to counsel about HPV (66.4%) and its vaccination (72.6%). A lower proportion felt similarly regarding dental hygienists. Parent age and sex were not correlated with comfort levels, but education levels (P = .021) and child vaccination statuses (P > .001) were. CONCLUSIONS: Parents are comfortable having discussions about HPV and the vaccine in the dental setting, especially with dentists. This may represent an additional setting where strong recommendations increase vaccine uptake. PRACTICAL IMPLICATIONS: Our findings emphasize an opportunity for the dental care team to improve the patient perspective on the role of dental care providers in HPV prevention. Continuing dental education can increase providers' knowledge, comfort, and confidence in discussing HPV with parents. Parents perceiving provider comfort and confidence might be more comfortable with HPV conversations. Training in collaborative, patient-focused communication techniques, such as motivational interviewing, can improve both providers' and patients' comfort and confidence in HPV counseling from oral health care providers.


Assuntos
Papillomaviridae , Infecções por Papillomavirus , Adolescente , Criança , Assistência Odontológica , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Minnesota , Pais , Vacinação
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