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1.
BMC Infect Dis ; 20(1): 808, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153446

RESUMO

BACKGROUND: Although more than 10 years have passed since HPV vaccination was implemented, first as an interim programme (Emergent vaccine promotion programme) in November 2010, followed by incorporating into the National Immunization Programme in April, 2013 and suspended in June 2013, limited studies have investigated the HPV vaccine effectiveness against high-grade cervical lesions in Japan. METHODS: We collected the matched data of the results of cervical biopsy and history of vaccination from the Japan Cancer Society database. The subjects were women aged 20 to 29 years screened for cervical cancer between April, 2015 and March, 2017, and with information on HPV vaccination status. We estimated the relative risk of developing high-grade cervical lesions in vaccinated subjects using Poisson regression as compared to unvaccinated subjects. RESULTS: Among the 34,281 women screened, 3770 (11.0%) were vaccinated. The prevalence of CIN2+ was statistically significantly lower in the vaccinated women as compared to the unvaccinated women (Vaccine Effectiveness (VE) =76%; RR = 0.24, 95% CI:0.10-0.60). High VE against CIN3+ was also observed (91%; RR = 0.09, 95% CI:0.00-0.42). CONCLUSION: Women aged 20-29 years who received at least one dose of HPV vaccine had a significantly lower risk of high-grade cervical lesions than those not vaccinated. In Japan, HPV vaccination should be resumed in order to reduce the incidence of cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Vacinação , Adulto , Neoplasia Intraepitelial Cervical/classificação , Neoplasia Intraepitelial Cervical/virologia , Estudos Transversais , Feminino , Humanos , Programas de Imunização , Incidência , Japão/epidemiologia , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/administração & dosagem , Prevalência , Resultado do Tratamento , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/virologia , Adulto Jovem
2.
Med Clin North Am ; 104(6): 1063-1078, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33099451

RESUMO

The most effective strategy for cervical cancer prevention involves vaccination to prevent human papillomavirus (HPV) infections during adolescence followed by screening to detect HPV infections during adulthood. HPV vaccination before sexual debut can prevent HPV infections, precancers, and cancers. HPV vaccination of sexually active populations does not prevent cancer. Screening with HPV testing is the most effective method of detecting precancers and cancers between ages 25 and 65. Ensuring adequate screening around the age of menopause may be the key to preventing cervical cancer among elderly women. Most cervical cancers at all ages occur among unscreened or underscreened women.


Assuntos
Neoplasias do Colo do Útero/prevenção & controle , Detecção Precoce de Câncer , Feminino , Humanos , Teste de Papanicolaou , Papillomaviridae/imunologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/prevenção & controle , Atenção Primária à Saúde , Estados Unidos , Neoplasias do Colo do Útero/patologia , Vacinação
3.
PLoS One ; 15(10): e0234693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33091021

RESUMO

BACKGROUND: The pathogenic and oncogenic roles of papillomavirus (HPV) infections have been documented and shown to occur in women as well as in men. While other countries have already extended their vaccination guidelines to include boys, in 2019 the French National Authority for Health validated implementation of HPV vaccination in the 2020 vaccination schedule. There is, however, a climate of distrust in regard to vaccination in France, and there have been few studies to date regarding the acceptability of HPV vaccination in boys in France. The aim of this study was, therefore, to evaluate the acceptability of extending the recommendations for HPV vaccination in men, among middle and high school students and their parents. METHODS: Our study (HPVac) was a prospective, multicenter, departmental, and descriptive survey applied to a sample of male middle and high school students attending schools in the Loire-Atlantique department and their parents. It took place from January 2017 to January 2018. RESULTS: We analyzed the information obtained from 127 parent questionnaires and 145 children questionnaires. In terms of acceptability, 36.6% (n = 53) of the children and 37.8% (n = 48) of the parents were in favour of being vaccinated or of having their children vaccinated against HPV (51.7% (n = 75) and 50.4% (n = 64), respectively, were undecided). The perception of a risk stemming from HPV infection was positively associated with acceptability of the HPV vaccine. Being against vaccines in general, being discouraged by their parents, parents thinking that their child is not at risk, and the belief that the vaccine is not mandatory were arguments cited and significantly associated with a willingness to be vaccinated. CONCLUSION: This study revealed a lack of information among boys and their parents about HPV and its vaccination. It also clearly showed that taking time to discuss the consequences of an infection and the merits of being vaccinated can help parents overcome their reluctance. The children then generally go along with their parent's choice.


Assuntos
Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Pais/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Estudantes/psicologia , Vacinação/psicologia , Adolescente , Adulto , Criança , Feminino , Seguimentos , França/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Prognóstico , Estudos Prospectivos , Instituições Acadêmicas , Inquéritos e Questionários , Adulto Jovem
4.
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
5.
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
6.
Nat Commun ; 11(1): 2841, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503989

RESUMO

The capsid of human papillomavirus (HPV) spontaneously arranges into a T = 7 icosahedral particle with 72 L1 pentameric capsomeres associating via disulfide bonds between Cys175 and Cys428. Here, we design a capsomere-hybrid virus-like particle (chVLP) to accommodate multiple types of L1 pentamers by the reciprocal assembly of single C175A and C428A L1 mutants, either of which alone encumbers L1 pentamer particle self-assembly. We show that co-assembly between any pair of C175A and C428A mutants across at least nine HPV genotypes occurs at a preferred equal molar stoichiometry, irrespective of the type or number of L1 sequences. A nine-valent chVLP vaccine-formed through the structural clustering of HPV epitopes-confers neutralization titers that are comparable with that of Gardasil 9 and elicits minor cross-neutralizing antibodies against some heterologous HPV types. These findings may pave the way for a new vaccine design that targets multiple pathogenic variants or cancer cells bearing diverse neoantigens.


Assuntos
Proteínas do Capsídeo/imunologia , Neoplasias/terapia , Papillomaviridae/imunologia , Infecções por Papillomavirus/terapia , Vacinas contra Papillomavirus/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Proteínas do Capsídeo/administração & dosagem , Proteínas do Capsídeo/genética , Desenho de Fármacos , Epitopos/genética , Epitopos/imunologia , Feminino , Humanos , Imunogenicidade da Vacina , Camundongos , Modelos Animais , Mutação , Neoplasias/virologia , Testes de Neutralização , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/genética , Multimerização Proteica/genética , Multimerização Proteica/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia
8.
Am J Surg Pathol ; 44(9): 1184-1191, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32496434

RESUMO

Tumor cell expression of major histocompatibility complex (MHC) class I is required for antigen presentation and adaptive immune recognition. Absent or diminished MHC class I expression is thought to contribute to immunotherapeutic resistance in some epithelial tumors but has not been previously studied in cervical and vulvar carcinoma. Given that anti-programmed cell death 1 (PD-1) checkpoint inhibition is deployed for programmed cell death ligand 1 (PD-L1)-positive recurrent and metastatic cervical squamous carcinomas, identifying tumors with loss of MHC class I is of clinical interest to optimize the selection of immunotherapeutic candidates. Immunohistochemistry for PD-L1 and MHC class I combined A, B, and C heavy chains (MHC class I) was assessed in 58 human papillomavirus-associated cervical and vulvar lesions, including 27 squamous intraepithelial lesions (SILs) and 31 invasive squamous cell carcinoma (SCC). Although 84% of SCC and 22% of SIL were PD-L1-positive, 35.5% (11/31) of SCC and 18.5% (5/27) of SIL also showed clonal or complete loss of MHC class I. Loss of MHC class I expression was more common in PD-L1-positive (10/26, 38%) versus PD-L1-negative SCC (1/5, 20%). In summary, over one third of human papillomavirus-associated cervical and vulvar SCC show clonal or complete loss of MHC class I expression, including many PD-L1-positive cases. This suggests that the efficacy of checkpoint inhibitors targeting the PD-1/PD-L1 axis may be limited in a subset of cervical and vulvar squamous neoplasms due to an impaired ability to engage with the adaptive immune system related to loss of MHC class I expression.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Escamosas/virologia , Resistencia a Medicamentos Antineoplásicos , Antígenos de Histocompatibilidade Classe I/imunologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/virologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/virologia , Neoplasias Vulvares/virologia , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Regulação para Baixo , Feminino , Interações Hospedeiro-Patógeno , Humanos , Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Estudos Retrospectivos , Lesões Intraepiteliais Escamosas Cervicais/tratamento farmacológico , Lesões Intraepiteliais Escamosas Cervicais/imunologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Neoplasias Vulvares/tratamento farmacológico , Neoplasias Vulvares/imunologia , Neoplasias Vulvares/patologia
9.
PLoS One ; 15(6): e0233499, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32484811

RESUMO

INTRODUCTION: The World Health Organization (WHO) recommends that human papillomavirus (HPV) vaccination programs are established to be cost-effective before implementation. WHO recommends HPV vaccination for girls aged 9-13 years to tackle the high burden of cervical cancer. This review examined the existing evidence on the cost-effectiveness of the 9-valent HPV vaccine within a global context. METHODS: The literature search covering a period of January 2000 to 31 July 2019 was conducted in PubMed and Scopus bibliographic databases. A combined checklist (i.e., WHO, Drummond and CHEERS) was used to examine the quality of eligible studies. A total of 12 studies were eligible for this review and most of them were conducted in developed countries. RESULTS: Despite some heterogeneity in approaches to measure cost-effectiveness, ten studies concluded that 9vHPV vaccination was cost-effective and two did not. The addition of adolescent boys into immunisation programs was cost effective when vaccine price and coverage was comparatively low. When vaccination coverage for females was more than 75%, gender neutral HPV vaccination was less cost-effective than vaccination targeting only girls aged 9-18 years. Multi cohort immunization approach was found cost-effective in the age range of 9-14 years. However, the upper age limit at which vaccination was found not cost-effective requires further evaluation. This review identified duration of vaccine protection, time horizon, vaccine price, coverage, healthcare costs, efficacy and discounting rates as the most dominating parameters in determining cost-effectiveness. CONCLUSIONS: These findings have implications in extending HPV immunization programs whether switching to the 9-valent vaccine or the inclusion of adolescent boys' vaccination or extending the age of vaccination. Further, this review also supports extending vaccination programs to low-resource settings where vaccine prices are competitive, donor funding is available, burden of cervical cancer is high and screening options are limited.


Assuntos
Papillomaviridae/imunologia , Vacinas contra Papillomavirus/economia , Adolescente , Criança , Estudos de Coortes , Análise Custo-Benefício/métodos , Feminino , Custos de Cuidados de Saúde , Humanos , Imunização/economia , Programas de Imunização/economia , Masculino , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Anos de Vida Ajustados por Qualidade de Vida , Vacinação/economia , Cobertura Vacinal/economia
10.
Cancer Immunol Immunother ; 69(10): 2089-2100, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32448984

RESUMO

INTRODUCTION: The importance of immune tumor microenvironment in the prognosis of patients with head and neck squamous carcinomas (HNSCC) is increasingly recognized. We analyzed the prognostic relevance of PD-L1 and PD-1 expressions in relation to the infiltration by CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs). METHODS: Samples from 372 surgically treated HPV-negative HNSCC patients were evaluated by immunohistochemistry for PD-L1 expression [both tumor proportion score (TPS) and combined proportion score (CPS)], PD-1 expression in immune cells, and density of infiltrating CD8+ and FOXP3+ TILs. PD-L1 expression and CD8+ TIL density were combined to establish the type of tumor microenvironment. RESULTS: 29.5% cases exhibited PD-L1 TPS positivity (≥ 1%), whereas PD-L1 CPS positivity (≥ 1%) was observed in 40% cases. 47.5% cases showed positive PD-1 expression (≥ 1%). PD-L1 and PD-1 positivity correlated with a high density of both CD8+ and FOXP3+ TILs. In univariate analysis, PD-L1 TPS positivity (P = 0.026), PD-L1 CPS positivity (P = 0.004), high density of CD8+ TIL (P = 0.001), and high density of FOXP3+ TIL (P = 0.004) were associated with a better disease-specific survival (DSS). However, in multivariate analysis, only high density of CD8+ TIL was associated with a better DSS (P = 0.002). The type of tumor microenvironment correlated with DSS (P = .008), with the better DSS observed in cases with type I (PD-L1 CPS positivity and high density of CD8+ TIL). CONCLUSIONS: High infiltration by CD8+ TIL is associated with better survival outcomes. Positive PD-L1 expression correlates with a high infiltration by TILs, explaining its association with better prognosis.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias de Cabeça e Pescoço/imunologia , Linfócitos do Interstício Tumoral/imunologia , Papillomaviridae/imunologia , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Microambiente Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Taxa de Sobrevida
11.
Int J STD AIDS ; 31(7): 606-612, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32438856

RESUMO

Human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide and ano-genital warts (AGWs) are highly infectious. This virus is transmitted through sexual, anal, or oral contact as well as skin-to-skin contacts. Treatment for this condition has significant morbidity and it can be frustrating in certain cases. The HPV vaccination has been demonstrated as a promising strategy of secondary prevention in HPV-related diseases such as head and neck cancers, cervical diseases, and recurrent respiratory papillomatosis. Regarding AGWs, it is unclear whether vaccination can provide analogous clinical benefit. The aim of this work is to systematically review the literature regarding HPV vaccination for secondary disease prevention after treatment of AGWs. From October to December 2018, a systematic search for clinical trials was conducted in five databases: PubMed, MEDLINE, EMBASE, Cochrane, and clinicaltrials.gov using a combination of the following descriptors: 'gardasil' OR 'cervarix' OR 'nine-valent' OR '9-valent' OR 'vaccine' AND 'recurrence' OR 'relapse' AND 'hpv' OR 'papillomavirus' AND 'warts' OR 'condyloma.' Data were synthetized and entered in the Review Manager software (RevMan 5.3.5) to perform the meta-analysis. The search yielded 824 potentially relevant studies. Two studies fulfilled the eligibility criteria involving 656 participants. The meta-analysis estimated the rate of recurrence of AGWs was similar between the vaccine group and the control group. The overall effect estimate was 1.02 (0.75-1.38). This is the first meta-analysis exploring the effect of HPV vaccine in preventing the relapse of AGWs. These results suggest that HPV vaccination does not provide secondary benefit in patients with previous AGWs. However, these results cannot be generalized due to the scarce number of RCTs currently available in the literature. The outcomes from future randomized controlled trials (RCTs) are warranted to further clarify the precise effect of the vaccine.


Assuntos
Canal Anal/virologia , Condiloma Acuminado/prevenção & controle , Papillomaviridae/imunologia , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Ânus/prevenção & controle , Neoplasias do Ânus/virologia , Condiloma Acuminado/virologia , Feminino , Neoplasias dos Genitais Femininos/prevenção & controle , Neoplasias dos Genitais Femininos/virologia , Neoplasias dos Genitais Masculinos/prevenção & controle , Neoplasias dos Genitais Masculinos/virologia , Humanos , Masculino , Infecções por Papillomavirus , Prevenção Secundária
12.
Arch Virol ; 165(6): 1441-1444, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32239294

RESUMO

Bovine papillomavirus type 9 (BPV9) is a causative agent of severe teat papillomatosis. Considering the lack of efficient BPV culture methods, recombinant proteins such as virus-like particles developed through genetic engineering may serve as a useful tool for developing effective vaccines against BPV infection. In this study, we successfully produced immunogenic particles composed of recombinant L1 protein of BPV9 (rBPV9-L1), using a baculovirus expression system. rBPV9-L1-immunized mice produced BPV9-specific IgG, which did not cross-react with BPV type 6, which is another causative agent of teat papillomatosis. Hence, immunogenic rBPV9-L1 is potentially applicable as a vaccine candidate for teat papillomatosis.


Assuntos
Proteínas do Capsídeo/imunologia , Doenças dos Bovinos/prevenção & controle , Papillomaviridae/imunologia , Infecções por Papillomavirus/veterinária , Vacinas de Partículas Semelhantes a Vírus/imunologia , Animais , Proteínas do Capsídeo/biossíntese , Bovinos , Doenças dos Bovinos/virologia , Feminino , Genótipo , Camundongos , Papillomaviridae/genética , Infecções por Papillomavirus/prevenção & controle , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/imunologia , Vacinação
13.
Nat Commun ; 11(1): 1999, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332850

RESUMO

Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16-26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies.


Assuntos
Neoplasia Intraepitelial Cervical/microbiologia , Microbiota/imunologia , Infecções por Papillomavirus/microbiologia , Neoplasias do Colo do Útero/microbiologia , Vagina/microbiologia , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/imunologia , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , Colo do Útero/virologia , Estudos de Coortes , DNA Bacteriano/isolamento & purificação , Feminino , Seguimentos , Gardnerella vaginalis/genética , Gardnerella vaginalis/imunologia , Gardnerella vaginalis/isolamento & purificação , Humanos , Lactobacillus/genética , Lactobacillus/imunologia , Lactobacillus/isolamento & purificação , Microbiota/genética , Estadiamento de Neoplasias , Papillomaviridae/imunologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/patologia , Prevotella/genética , Prevotella/imunologia , Prevotella/isolamento & purificação , RNA Ribossômico 16S/genética , Fatores de Risco , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Adulto Jovem
14.
J Virol ; 94(12)2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32295905

RESUMO

We demonstrate that female C57BL/6J mice are susceptible to a transient lower genital tract infection with MmuPV1 mouse papillomavirus and display focal histopathological abnormalities resembling those of human papillomavirus (HPV) infection. We took advantage of strains of genetically deficient mice to study in vivo the role of innate immune signaling in the control of papillomavirus. At 4 months, we sacrificed MmuPV1-infected mice and measured viral 757/3139 spliced transcripts by TaqMan reverse transcription-PCR (RT-PCR), localization of infection by RNAscope in situ hybridization, and histopathological abnormities by hematoxylin and eosin (H&E) staining. Among mice deficient in receptors for pathogen-associated molecular patterns, MyD88-/- and STING-/- mice had 1,350 and 80 copies of spliced transcripts/µg RNA, respectively, while no viral expression was detected in MAVS-/- and Ripk2-/- mice. Mice deficient in an adaptor molecule, STAT1-/-, for interferon signaling had 46,000 copies/µg RNA. Among mice with targeted deficiencies in the inflammatory response, interleukin-1 receptor knockout (IL-1R-/-) and caspase-1-/- mice had 350 and 30 copies/µg RNA, respectively. Among mice deficient in chemokine receptors, CCR6-/- mice had 120 copies/µg RNA, while CXCR2-/- and CXCR3-/- mice were negative. RNAscope confirmed focal infection in MyD88-/-, STAT1-/-, and CCR6-/- mice but was negative for other gene-deficient mice. Histological abnormalities were seen only in the latter mice. Our findings and the literature support a working model of innate immunity to papillomaviruses involving the activation of a MyD88-dependent pathway and IL-1 receptor signaling, control of viral replication by interferon-stimulated genes, and clearance of virus-transformed dysplastic cells by the action of the CCR6/CCL20 axis.IMPORTANCE Papillomaviruses infect stratified squamous epithelia, and the viral life cycle is linked to epithelial differentiation. Additionally, changes occur in viral and host gene expression, and immune cells are activated to modulate the infectious process. In vitro studies with keratinocytes cannot fully model the complex viral and host responses and do not reflect the contribution of local and migrating immune cells. We show that female C57BL/6J mice are susceptible to a transient papillomavirus cervicovaginal infection, and mice deficient in select genes involved in innate immune responses are susceptible to persistent infection with variable manifestations of histopathological abnormalities. The results of our studies support a working model of innate immunity to papillomaviruses, and the model provides a framework for more in-depth studies. A better understanding of mechanisms of early viral clearance and the development of approaches to induce clearance will be important for cancer prevention and the treatment of HPV-related diseases.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Fator 88 de Diferenciação Mieloide/imunologia , Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , RNA Mensageiro/imunologia , RNA Viral/imunologia , Receptores Tipo I de Interleucina-1/imunologia , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Processamento Alternativo , Animais , Caspase 1/deficiência , Caspase 1/genética , Caspase 1/imunologia , Colo do Útero/imunologia , Colo do Útero/virologia , Feminino , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Imunidade Inata , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/deficiência , Fator 88 de Diferenciação Mieloide/genética , Papillomaviridae/crescimento & desenvolvimento , Papillomaviridae/metabolismo , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , RNA Mensageiro/genética , RNA Viral/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/deficiência , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/imunologia , Receptores CCR6/deficiência , Receptores CCR6/genética , Receptores CCR6/imunologia , Receptores CXCR3/deficiência , Receptores CXCR3/genética , Receptores CXCR3/imunologia , Receptores Tipo I de Interleucina-1/deficiência , Receptores Tipo I de Interleucina-1/genética , Receptores de Interleucina-8B/deficiência , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/imunologia , Fator de Transcrição STAT1/deficiência , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/imunologia , Transdução de Sinais , Vagina/imunologia , Vagina/virologia
15.
Best Pract Res Clin Obstet Gynaecol ; 65: 109-124, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32284298

RESUMO

Prophylactic vaccines have been found to be highly effective in preventing infection and pre-invasive and invasive cervical, vulvovaginal and anal disease caused by the vaccine types. HPV vaccines contain virus-like particles that lack the viral genome and produce high titres of neutralising antibodies. Although the vaccines are highly effective in preventing infections, they do not enhance clearance of existing infections. Vaccination programmes target prepubertal girls and boys prior to sexual debut as efficacy is highest in HPV naïve individuals. School-based programmes achieve higher coverage, although implementation is country specific. Vaccination of older women may offer some protection and acceleration of impact, although this may not be cost-effective. HPV-based screening will continue for vaccinated cohorts, although intervals may increase.


Assuntos
Programas de Rastreamento/métodos , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/prevenção & controle , Vacinação , Idoso , Análise Custo-Benefício , Feminino , Humanos , Masculino , Papillomaviridae/imunologia , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia
16.
Cancer Cytopathol ; 128(4): 227-228, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32251554
17.
West J Emerg Med ; 21(2): 203-208, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32191177

RESUMO

INTRODUCTION: A vaccine targeting high-risk human papillomavirus (HPV) strains can effectively prevent HPV-associated cervical cancer risk. However, many girls and women do not receive the vaccine, more often those impacted by health disparities associated with race and/or socioeconomic status. This same disparate population has also been shown to be at higher risk for cervical cancer. Many of these women also rely on the emergency department (ED) as a safety net for their healthcare. This study sought to gather information pertaining to HPV and cervical cancer risk factors, awareness of HPV and the vaccine, as well as HPV vaccine uptake in female patients presenting to an ED. METHODS: We obtained 81 surveys completed by female ED patients. Demographics included age, race, income, insurance status, primary care provider status, and known cervical-cancer risk factors. Subsequent survey questions explored respondents' knowledge, familiarity, and attitudes regarding HPV, cervical cancer, and the HPV vaccine, including vaccination uptake rates. We analyzed data using descriptive statistics and Fisher's exact test. RESULTS: Approximately one in seven respondents (14.8%) had never previously heard of HPV and 32.1% were unaware of the existence of a HPV vaccine. Minority patients, including those who were Black and Hispanic patients, low income patients, and uninsured and publicly insured patients were less likely to be aware of HPV and the vaccine and likewise were less likely to be offered and receive the vaccine. More than 60% of all respondents (61.3%) had never previously been offered the vaccine, and only 24.7% of all respondents had completed the vaccine series. CONCLUSION: Female ED patients may represent an at-risk cohort with relatively low HPV awareness and low HPV vaccine uptake. The ED could represent a novel opportunity to access and engage high-risk HPV populations.


Assuntos
Serviço Hospitalar de Emergência , Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Vacinação/métodos , Adolescente , Adulto , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Grupos Minoritários , Infecções por Papillomavirus/epidemiologia , Pobreza , Fatores de Risco , Inquéritos e Questionários , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero , Adulto Jovem
18.
Cancer Invest ; 38(4): 228-239, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32208057

RESUMO

The aim of this study was to characterize both by flow cytometry analysis and immunohistochemistry cervix uteri cells of nulliparous women screened for cervical intraepithelial neoplasia (CIN) in comparison to a group without CIN by using mesenchymal stem cell-like and hematopoietic lineage markers. A significant expression for CD29, CD38, HLA-I, and HLA-II was correlated positively to the CIN degree and it was more relevant in patients positive for human papilloma virus (HPV). Thus, identification and detailed characterization of pluripotent resident in uteri cells could be a promising therapeutic target.


Assuntos
Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/citologia , Células-Tronco Neoplásicas/patologia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , ADP-Ribosil Ciclase 1/análise , ADP-Ribosil Ciclase 1/imunologia , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Biópsia , Neoplasia Intraepitelial Cervical/imunologia , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/imunologia , Colo do Útero/patologia , Colo do Útero/virologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe I/análise , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe II/análise , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Integrina beta1/análise , Integrina beta1/imunologia , Integrina beta1/metabolismo , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , Gradação de Tumores , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/virologia , Papillomaviridae/imunologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia
19.
Ann N Y Acad Sci ; 1470(1): 44-56, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32170783

RESUMO

High-risk human papillomavirus (HPV) types 16/18 have been associated with Barrett's dysplasia (BD)/esophageal adenocarcinoma (EAC). Nevertheless, no data exist in relation to serological analysis for HPV antibodies in BD/EAC with site-specific viral DNA status. We prospectively examined antibodies to multiple HPV types in 438 patients representing hospital/reflux controls and Barrett's metaplasia (BM)/BD/intramucosal EAC. Antibody responses to HPV6/11/16/18/31/33/45/52/58 were analyzed using multiplex serology, including antibodies to E6/E7/E1/E2 and L1 antigens. Seropositivity for individual HPV proteins was infrequent in both cases and controls and was ≤10.2%. There was no difference in the seroprevalence of antibodies to any HPV antigen/antibody combination between reclassified cases (BD/EAC) and controls (hospital/reflux/BM) or between HPV16 or HPV18 DNA cases and controls, respectively. Among HPV16 DNA-positive BD/EAC cases, antibodies to HPV16 E7 were significantly more prevalent (3/26, 11.5%) than in hospital and reflux controls plus BM (5/328, 1.5%) (adjusted OR = 10.12, 95% CI: 1.61-63.73, P = 0.014). Among HPV18 DNA-positive cases, antibodies to HPV18 E1 were present in 3/6 (50%) cases versus 5/328 (1.5%) controls (adjusted OR = 44.28, 95% CI: 6.10-321.47, P = 0.0002). Although antibodies against HPV were generally uncommon in cases and controls, immune responses against two early proteins of HPV16/18 were significantly more frequent in viral DNA-positive BD/intramucosal EAC.


Assuntos
Adenocarcinoma/imunologia , Esôfago de Barrett/imunologia , Neoplasias Esofágicas/imunologia , Papillomaviridae/imunologia , Adenocarcinoma/patologia , Adulto , Idoso , Esôfago de Barrett/patologia , Estudos Transversais , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos
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