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1.
Cancer Sci ; 112(4): 1402-1416, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33529452

RESUMO

Human papillomavirus (HPV) is an important etiological factor of head and neck squamous cell carcinoma (HNSCC). HPV+ HNSCC patients usually have a better prognosis, which probably results from the higher infiltration of B lymphocytes. This study was purposed to detect the infiltration of B lymphocyte subsets and the correlation between B lymphocyte subsets and the prognosis in HPV-related HNSCC. In this study, 124 HPV+ and 513 HPV- HNSCC samples were obtained from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database for transcriptomic analysis. Infiltration of B lymphocytes subsets was detected with 7 HPV+ HNSCC and 13 HPV- HNSCC tissues through immunohistochemistry and immunofluorescence. One HPV- HNSCC sample was detected with single-cell sequencing for chemokine analysis. In the results, the infiltration of plasma cells (CD19+ CD38+ ) and memory B cells (MS4A1+ CD27+ ) was higher in HPV+ HNSCC samples. High infiltration of plasma cells and memory B cells was related to a better prognosis. High density of B lymphocytes was positively correlated with high CXCL13 production mainly from CD4+ T lymphocytes in HNSCC. These results indicated that a high density of plasma cells and memory B cells could predict excellent prognosis. CD4+ T lymphocytes might affect B lymphocytes and their subsets through the CXCL13/CXCR5 axis in HNSCC.


Assuntos
Alphapapillomavirus/imunologia , Linfócitos B/imunologia , Carcinoma de Células Escamosas/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Idoso , Linfócitos T CD4-Positivos/imunologia , Carcinoma de Células Escamosas/virologia , Quimiocina CXCL13/imunologia , Feminino , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Prognóstico , Receptores CXCR5/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
2.
Viruses ; 13(2)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498165

RESUMO

Anal squamous cell carcinoma is the most frequent virus-related non-AIDS-defining neoplasia among HIV-infected individuals, especially MSM. The objectives of this study were to analyze the effectiveness of the quadrivalent HPV (qHPV) vaccine to prevent anal ≥ high-grade squamous intraepithelial lesions (≥HSILs), external ano-genital lesions (EAGLs), and infection by qHPV vaccine genotypes in HIV+ MSM, and to study the immunogenicity of the vaccine and risk factors for ≥ HSILs. This study is nested within a randomized, double-blind, placebo-controlled trial of the qHPV vaccine, which enrolled participants between May 2012 and May 2014, with a 48-month follow-up. A vaccine or placebo was administered at 0, 2, and 6 months, and vaccine antibody titers were evaluated at 7, 12, 24, 36, and 48 months. Data were gathered at 12, 24, 36, and 48 months on sexual habits, CD4/CD8 cell/counts, HIV viral load, and the results of cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope). The study included 129 patients (mean age of 38.8 years, 40 [31%] with a history of AIDS, 119 [92.2%] receiving ART, and 4 [3.3%] with virological failure), 66 (51.2%) in vaccine arm and 63 (48.4%) in placebo arm. The vaccine and placebo groups did not differ in ≥ HSILs (14.1 vs. 13.1%, respectively, p = 0.98) or EAGL (11.1 vs. 6.8%, p = 0.4) rates during follow-up; however, a protective effect against HPV 6 was observed during the first year of follow-up in the vaccine versus placebo group (7.5% vs. 23.4%; p = 0.047). A between-arm difference (p = 0.0001) in antibodies against qHPV vaccine genotypes was observed at 7 months (76.9% in vaccine arm vs. 30.2% in placebo arm), 12 months (68.1% vs. 26.5%), 24 months (75% vs. 32.5%), 36 months (90% vs. 24.4%), and 48 months (87.2% vs. 30%). Finally, the factor associated with the risk of anal ≥ HSIL onset during the four-year follow-up was the receipt of the last dose of the vaccine less than 6 months earlier in comparison to those vaccinated for a longer period (82.4% vs. 17.6% (OR 0.869 [95% CI, 0.825-0.917]). Vaccine and placebo arms did not significantly differ in ≥ HSIL or EAGL rates or in protection against infection by HPV genotype vaccine except for HPV6 at 12 months after the first dose. A long-lasting immune response was observed in almost all the vaccinated men. The main protective factor against ≥ HSIL was to have completed the vaccination regimen more than 6 months earlier.


Assuntos
Anticorpos Antivirais/sangue , Neoplasias do Ânus/prevenção & controle , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Infecções por Papillomavirus/prevenção & controle , Adulto , Canal Anal/virologia , Neoplasias do Ânus/virologia , Contagem de Linfócito CD4 , Coinfecção/virologia , Infecções por HIV/virologia , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Análise de Regressão , Minorias Sexuais e de Gênero , Espanha , Carga Viral/imunologia
3.
Methods Mol Biol ; 2197: 241-252, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32827141

RESUMO

Human papillomavirus (HPV) is a contagious cause of anogenital and oropharyngeal cancers developing from persistently infected and subsequently transformed basal keratinocytes of mucosal epithelium. DNA-based immunotherapy offers great potential for the treatment of persisting HPV infections and associated cancers. Preclinical testing of therapeutic DNA-based HPV-targeted immunotherapy requires robust animal models which mimic HPV-associated cancer disease in humans. Here we describe a detailed protocol of intradermal delivery of a therapeutic DNA vaccine and a grafting model of neoantigen expressing skin to evaluate vaccine efficacy against HPV16 mediated hyperproliferative epithelium in mice.


Assuntos
Vacinas Anticâncer/imunologia , Papillomavirus Humano 16/imunologia , Neoplasias/etiologia , Neoplasias/terapia , Infecções por Papillomavirus/complicações , Vacinas contra Papillomavirus/imunologia , Vacinas de DNA/imunologia , Animais , Vacinas Anticâncer/administração & dosagem , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Imunização , Injeções Subcutâneas , Camundongos , Camundongos Transgênicos , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas de DNA/administração & dosagem
4.
Int J Cancer ; 148(2): 277-284, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32638362

RESUMO

The age-standardised incidence of cervical cancer in Europe varies widely by country (between 3 and 25/100000 women-years) in 2018. Human papillomavirus (HPV) vaccine coverage is low in countries with the highest incidence and screening performance is heterogeneous among European countries. A broad group of delegates of scientific professional societies and cancer organisations endorse the principles of the WHO call to eliminate cervical cancer as a public health problem, also in Europe. All European nations should, by 2030, reach at least 90% HPV vaccine coverage among girls by the age of 15 years and also boys, if cost-effective; they should introduce organised population-based HPV-based screening and achieve 70% of screening coverage in the target age group, providing also HPV testing on self-samples for nonscreened or underscreened women; and to manage 90% of screen-positive women. To guide member states, a group of scientific professional societies and cancer organisations engage to assist in the rollout of a series of concerted evidence-based actions. European health authorities are requested to mandate a group of experts to develop the third edition of European Guidelines for Quality Assurance of Cervical Cancer prevention based on integrated HPV vaccination and screening and to monitor the progress towards the elimination goal. The occurrence of the COVID-19 pandemic, having interrupted prevention activities temporarily, should not deviate stakeholders from this ambition. In the immediate postepidemic phase, health professionals should focus on high-risk women and adhere to cost-effective policies including self-sampling.


Assuntos
Alphapapillomavirus/imunologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Saúde Pública/métodos , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Alphapapillomavirus/fisiologia , /prevenção & controle , Detecção Precoce de Câncer , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Saúde Pública/normas , Saúde Pública/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/imunologia , Vacinação/métodos , Organização Mundial da Saúde , Adulto Jovem
5.
PLoS One ; 15(10): e0240154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33007050

RESUMO

BACKGROUND: The burden of HPV-associated premalignant and malignant cervical lesions remains high in HIV+ women even under ART treatment. In order to identify possible underlying pathophysiologic mechanisms, we studied activation and HIV co-receptor expression in cervical T-cell populations in relation to HIV, HPV and cervical lesion status. METHODS: Cervical cytobrush (n = 468: 253 HIV- and 215 HIV+; 71% on ART) and blood (in a subset of 39 women) was collected from women in Mbeya, Tanzania. Clinical data on HIV and HPV infection, as well as ART status was collected. T cell populations were characterized using multiparametric flow cytometry-based on their expression of markers for cellular activation (HLA-DR), and memory (CD45RO), as well as HIV co-receptors (CCR5, α4ß7). RESULTS: Cervical and blood T cells differed significantly, with higher frequencies of T cells expressing CD45RO, as well as the HIV co-receptors CCR5 and α4ß7 in the cervical mucosa. The skewed CD4/CD8 T cell ratio in blood of HIV+ women was mirrored in the cervical mucosa and HPV co-infection was linked to lower levels of mucosal CD4 T cells in HIV+ women (%median: 22 vs 32; p = 0.04). In addition, HIV and HPV infection, and especially HPV-associated cervical lesions were linked to significantly higher frequencies of HLA-DR+ CD4 and CD8 T cells (p-values < 0.05). Interestingly, HPV infection did not significantly alter frequencies of CCR5+ or α4ß7+ CD4 T cells. CONCLUSION: The increased proportion of activated cervical T cells associated with HPV and HIV infection, as well as HPV-associated lesions, together with the HIV-induced depletion of cervical CD4 T cells, may increase the risk for HPV infection, associated premalignant lesions and cancer in HIV+ women. Further, high levels of activated CD4 T cells associated with HPV and HPV-associated lesions could contribute to a higher susceptibility to HIV in HPV infected women.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Colo do Útero/patologia , Infecções por HIV/imunologia , Linfócitos Intraepiteliais/imunologia , Ativação Linfocitária/imunologia , Depleção Linfocítica , Infecções por Papillomavirus/imunologia , Adulto , Colo do Útero/imunologia , Feminino , Infecções por HIV/sangue , Antígenos HLA-DR/metabolismo , Humanos , Integrinas/metabolismo , Contagem de Linfócitos , Pessoa de Meia-Idade , Infecções por Papillomavirus/sangue , Fenótipo , Receptores CCR5/metabolismo
6.
Obstet Gynecol ; 136(2): 435-436, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32732765

RESUMO

Human papillomavirus (HPV) causes significant morbidity and mortality in women and men. The HPV vaccine significantly reduces the incidence of anogenital cancer and genital warts in women and in men. Human papillomavirus vaccines are among the most effective vaccines available worldwide, with unequivocal data demonstrating greater than 99% efficacy when administered to women who have not been exposed to that particular type of HPV. Obstetrician-gynecologists and other health care professionals should strongly recommend HPV vaccination to eligible patients and stress the benefits and safety of the HPV vaccine. Further, obstetrician-gynecologists are encouraged to stock and administer HPV vaccines in their offices when feasible. Ideally, the HPV vaccine should be given in early adolescence because vaccination is most effective before exposure to HPV through sexual activity. Unvaccinated women age 26 years and younger should receive the HPV vaccine series regardless of sexual activity, prior exposure to HPV or sexual orientation. The HPV vaccine is now licensed in the United States for women and men through age 45 years. For some women aged 27-45 years who are previously unvaccinated, obstetrician-gynecologists and other health care professionals may use shared clinical decision making regarding HPV vaccination, considering the patient's risk for acquisition of a new HPV infection and whether the HPV vaccine may provide benefit.


Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Vacinação/normas , Adolescente , Adulto , Comitês Consultivos , Criança , DNA Viral , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/imunologia , Guias de Prática Clínica como Assunto , Sociedades Médicas , Estados Unidos , Adulto Jovem
7.
Autoimmun Rev ; 19(9): 102603, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32659478

RESUMO

More than one-fourth of all Persian gulf war coalition soldiers remain seriously ill. Several epidemiological studies suggest a link between multiple vaccinations at the time of the military operation and the illness development. Macrophagic Myofasciitis and post-HPV vaccination syndrome are two newer controversial vaccine-related disabling ailments. OBJECTIVES: 1) To systematically review all original articles investigating the association of vaccines with gulf war illness, 2) To discuss gulf war illness, Macrophagic Myofasciitis, and post-HPV vaccination syndrome clinical similarities, 3) To discuss emergent pathogenetic mechanisms proposed for post-HPV vaccination syndrome that may be also relevant to gulf war illness and Macrophagic Myofasciitis. RESULTS: All original epidemiological studies (n = 11) found a positive association between vaccination and gulf war illness development. Chronic fatigue, widespread pain and cognitive impairment characterize the three syndromes under discussion. Anti-adrenergic receptor antibodies, dysautonomia and small fiber neuropathy have been recently described in patients with post-HPV vaccination syndrome. CONCLUSION: post-HPV vaccination syndrome, Macrophagic Myofasciitis, and gulf war illness analogy suggests that some vaccines or multiple vaccinations in a very short period of time may induce, in susceptible individuals, chronic pain, fatigue and dyscognition. Vaccine-induced autoimmune dysautonomia is hypothesized as the common pathogenetic mechanism for this symptom cluster. Further research on the presence of small fiber neuropathy, adrenergic receptor antibodies, and abnormal autonomic function tests in the three syndromes under discussion may help to elucidate this hypothesis.


Assuntos
Fasciite/etiologia , Guerra do Golfo , Miosite/etiologia , Infecções por Papillomavirus/prevenção & controle , Disautonomias Primárias/etiologia , Vacinação/efeitos adversos , Vacinas/efeitos adversos , Fasciite/epidemiologia , Humanos , Miosite/epidemiologia , Infecções por Papillomavirus/imunologia , Disautonomias Primárias/epidemiologia , Disautonomias Primárias/imunologia , Vacinação/estatística & dados numéricos
8.
J Med Microbiol ; 69(7): 960-970, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32510304

RESUMO

Introduction. Persistent human papillomavirus (HPV) type 16 infection is the main causal agent of cervical cancer. Most HPV infections clear spontaneously within 1-2 years. Although not all infected women develop detectable HPV antibodies, about 60-70 % seroconvert and retain their antibodies at low levels.Aim. We investigated if cervical HPV16 DNA positivity was associated with HPV16 seroreactivity measured with two different antigen formulations. We assessed if associations were influenced by co-infection with other HPV types and HPV16 viral load.Methodology. We used baseline data for women participating in the Ludwig-McGill cohort, a longitudinal investigation of the natural history of HPV infection and cervical neoplasia. The study enrolled 2462 Brazilian women from 1993 to 1997 (pre-vaccination). ELISA assays were based on L1-only or L1+L2 virus-like particles (VLPs). Seroreactivity was expressed as normalized absorbance ratios. HPV genotyping and viral load were evaluated by PCR protocols. Pearson's r was used to measure correlations between interval-scaled variables. Serological accuracy in HPV16 DNA detection was assessed using receiver operating characteristic (ROC) curves. We analysed the association between HPV DNA positivity and HPV16 seroreactivity by linear regression.Results. Correlations between L1+L2 and L1-only VLPs for detection of HPV16 were poor (r=0.43 and 0.44 for dilutions 1 : 10 and 1 : 50, respectively). The protocol with the best accuracy was L1+L2 VLPs at serum dilution 1 : 10 (ROC area=0.73, 95 % CI: 0.65-0.85). HPV16 DNA positivity was correlated with HPV16 seroreactivity and was not influenced by co-infection or viral load. To a lesser degree, HPV16 seroreactivity was correlated with infection by other Alpha-9 papillomavirus species.Conclusion. HPV16 DNA positivity and HPV16 seroreactivity are strongly correlated. L1+L2 VLPs perform better than L1-only VLPs for detecting IgG antibodies to HPV16 in women infected with HPV16 or other Alpha-9 HPV species. This study advances our understanding of humoral immune responses against HPV16 by providing insights about the influence of VLP antigen composition to measure humoral immune response against naturally acquired HPV infection.


Assuntos
Papillomavirus Humano 16/genética , Papillomavirus Humano 16/imunologia , Infecções por Papillomavirus/diagnóstico , Adulto , Anticorpos Antivirais/sangue , Brasil , Capsídeo/imunologia , Proteínas do Capsídeo/genética , Colo do Útero/virologia , Estudos de Coortes , Feminino , Papillomavirus Humano 16/patogenicidade , Humanos , Complexo Antígeno L1 Leucocitário/imunologia , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/imunologia , Papillomaviridae/genética , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/imunologia , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Carga Viral/métodos , Vírion/imunologia
9.
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
10.
Sci Rep ; 10(1): 7306, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350356

RESUMO

Several determining factors are involved in HPV infection outcomes; human leukocyte antigen (HLA) polymorphisms have been described as related factors. This study has ascertained the effect of genetic variation on HLA-DRB1 and DQB1 genes on HPV-16/-18/-31/-33/-45 and -58 clearance and redetection in Colombian women. PCR and qPCR were used for viral identification and the Illumina MiSeq system was used for HLA-typing of cervical samples (n = 276). Survival models were adjusted for identifying alleles/haplotypes related to HPV clearance/redetection; L1/L2 protein-epitope binding to MHC-II molecules was also predicted. Significant associations suggested effects favouring or hampering clearance/redetection events depending on the viral type involved in infection, e.g. just DRB1*12:01:01G favoured HPV-16 (coeff: 4.8) and HPV-45 clearance (coeff: 12.65) whilst HPV-18 (coeff: 2E-15), HPV-31 (coeff: 8E-17) and HPV-58 hindered elimination (coeff: 1E-14). An effect was only observed for some alelles when configured as haplotypes, e.g. DRB1*04:07:01G (having the greatest frequency in the target population) was associated with DQB1*02:01:1G or *03:02:03. Epitope prediction identified 23 clearance-related peptides and 29 were redetection-related; eight might have been related to HPV-16/-18 and -58 persistence and one to HPV-18 elimination. HLA allele/haplotype relationship with the course of HPV infection (clearance/redetection) depended on the infecting HPV type, in line with the specific viral epitopes displayed.


Assuntos
Alelos , Alphapapillomavirus , Epitopos , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Haplótipos , Infecções por Papillomavirus , Adulto , Alphapapillomavirus/genética , Alphapapillomavirus/imunologia , Intervalo Livre de Doença , Epitopos/genética , Epitopos/imunologia , Feminino , Seguimentos , Cadeias beta de HLA-DQ/genética , Cadeias beta de HLA-DQ/imunologia , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/mortalidade , Taxa de Sobrevida
11.
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
12.
PLoS One ; 15(5): e0233084, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32421735

RESUMO

BACKGROUND: Cervical cancer associated with high risk-human papillomavirus (HR-HPV) infection is becoming the one of the most common female cancer in many sub-Saharan African countries. First-generation immigrant African women living in Europe are at-risk for cervical cancer, in a context of social vulnerability, with frequent lack of cervical cancer screening and HPV vaccination. OBJECTIVE: Our objective was to address immunologically the issue of catch-up prophylactic HPV vaccination in first-generation African immigrant women living in France. METHODS: IgG immune responses and cross-reactivities to α7 (HPV-18, -45 and -68) and α9 (HPV-16, -31, -33, -35, -52 and -58) HPV types, including 7 HR-HPV targeted by the Gardasil-9® prophylactic vaccine, were evaluated in paired serum and cervicovaginal secretions (CVS) by HPV L1-virus-like particles-based ELISA. Genital HPV were detected by multiplex real time PCR (Seegene, Seoul, South Korea). RESULTS: Fifty-one immigrant women (mean age, 41.7 years; 72.5% HIV-infected) were prospectively included. More than two-third (68.6%) of them carried genital HPV (group I) while 31.4% were negative (group II). The majority (90.2%) exhibited serum IgG to at least one α7/α9 HR-HPV. Serum HPV-specific IgG were more frequently detected in group I than group II (100% versus 68.7%; P = 0.002). The distribution of serum and genital HPV-specific IgG was similar, but mean number of IgG reactivities to α7/α9 HR-HPV was higher in serum than CVS (5.6 IgG per woman in serum versus 3.2 in CVS; P<0.001). Rates of IgG cross-reactivities against HPV different from detected cervicovaginal HPV were higher in serum and CVS in group I than group II. Finally, the majority of groups I and II women (68.6% and 68.7%, respectively) exhibited serum or cervicovaginal IgG to Gardasil-9® HR-HPV, with higher mean rates in group I than group II (6.1 Gardasil-9® HR-HPV per woman versus 1.4; P<0.01). One-third (31.2%) of group II women did not show any serum and genital HPV-specific IgG. CONCLUSIONS: Around two-third of first-generation African immigrant women living in France showed frequent ongoing genital HPV infection and high rates of circulating and genital IgG to α7/α9 HPV, generally cross-reacting, avoiding the possibility of catch-up vaccination. Nevertheless, about one-third of women had no evidence of previous HPV infection, or showed only low levels of genital and circulating HR-HPV-specific IgG and could therefore be eligible for catch-up vaccination.


Assuntos
Anticorpos Antivirais/metabolismo , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/virologia , Adulto , África ao Sul do Saara/etnologia , Anticorpos Antivirais/sangue , Colo do Útero/imunologia , Detecção Precoce de Câncer , Emigrantes e Imigrantes/estatística & dados numéricos , Feminino , França/etnologia , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/imunologia , Neoplasias do Colo do Útero/imunologia , Vagina/imunologia
13.
J Virol ; 94(15)2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32404527

RESUMO

Orf virus (ORFV) represents a suitable vector for the generation of efficient, prophylactic antiviral vaccines against different pathogens. The present study investigated for the first time the therapeutic application of ORFV vector-based vaccines against tumors induced by cottontail rabbit papillomavirus (CRPV). ORFV-CRPV recombinants were constructed expressing the early CRPV gene E1, E2, E7, or LE6. In two independent experiments we used in total 23 rabbits which were immunized with a mixture of the four ORFV-CRPV recombinants or empty ORFV vector as a control 5 weeks after the appearance of skin tumors. For the determination of the therapeutic efficacy, the subsequent growth of the tumors was recorded. In the first experiment, we could demonstrate that three immunizations of rabbits with high tumor burden with the combined four ORFV-CRPV recombinants resulted in significant growth retardation of the tumors compared to the control. A second experiment was performed to test the therapeutic effect of 5 doses of the combined vaccine in rabbits with a lower tumor burden than in nonimmunized rabbits. Tumor growth was significantly reduced after immunization, and one vaccinated rabbit even displayed complete tumor regression until the end of the observation period at 26 weeks. Results of delayed-type hypersensitivity (DTH) skin tests suggest the induction of a cellular immune response mediated by the ORFV-CRPV vaccine. The data presented show for the first time a therapeutic potential of the ORFV vector platform and encourage further studies for the development of a therapeutic vaccine against virus-induced tumors.IMPORTANCE Viral vectors are widely used for the development of therapeutic vaccines for the treatment of tumors. In our study we have used Orf virus (ORFV) strain D1701-V for the generation of recombinant vaccines expressing cottontail rabbit papillomavirus (CRPV) early proteins E1, E2, LE6, and E7. The therapeutic efficacy of the ORFV-CRPV vaccines was evaluated in two independent experiments using the outbred CRPV rabbit model. In both experiments the immunization achieved significant suppression of tumor growth. In total, 84.6% of all outbred animals benefited from the ORFV-CRPV vaccination, showing reduction in tumor size and significant tumor growth inhibition, including one animal with complete tumor regression without recurrence.


Assuntos
Vacinas Anticâncer/imunologia , Papillomavirus de Coelho Cottontail/imunologia , Neoplasias/terapia , Vírus do Orf/imunologia , Infecções por Papillomavirus/terapia , Vacinas Virais/imunologia , Animais , Vacinas Anticâncer/genética , Chlorocebus aethiops , Papillomavirus de Coelho Cottontail/genética , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/virologia , Vírus do Orf/genética , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/imunologia , Coelhos , Células Vero , Proteínas Virais/genética , Proteínas Virais/imunologia , Vacinas Virais/genética
14.
Crit Rev Oncol Hematol ; 150: 102966, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32371338

RESUMO

BACKGROUND: Despite multiple modalities used to management of head and neck squamous cell carcinoma (HNSCC), disease control remains unsatisfactory. Immunotherapy is emerging as a novel therapeutic approach. This systematic review assesses clinical data regarding immunotherapy efficacy and safety. METHODS: Data from 11 clinical trials testing immunotherapy in HNSCC were assessed. We performed the meta-analysis to correlate the overall survival (OS), response rate (RR), adverse effects, HPV status, and PD-L1 expression. RESULTS: Immunotherapy extended OS (hazard ratio = 0.77, p < 0.0001) and RR significantly (risk ratio = 1.41, p = 0.02). Patients with HPV-positive HNSCC exhibited a better RR (risk ratio = 1.29, p = 0.24) and OS (11.5 vs. 6.3 months). PD-L1 positive tumors showed a higher OS (9.9 vs. 6.5 months). Moreover, immunotherapy caused less adverse effects than standard therapy. CONCLUSION: Our results indicate the benefit of immunotherapy for improving RR and OS of HNSCC patients. The benefit is higher in patients with HPV and PD-L1 positive tumors.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Imunoterapia/métodos , Infecções por Papillomavirus/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Imuno-Histoquímica , Fatores Imunológicos , Terapia de Alvo Molecular , Papillomaviridae , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Resultado do Tratamento
15.
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
16.
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
17.
PLoS One ; 15(3): e0230106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160246

RESUMO

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is characterized by repeated formation of papillomas in the respiratory tract and is caused by human papillomavirus (HPV) types 6 and 11. Women with genital HPV infection are slow to develop weak humoral immunity, but respond robustly to the HPV vaccine. We wondered if people with RRP had a similar immune response. METHODS: A convenience cross-sectional sample of patients with RRP were recruited into one of four groups: 1) adults and adolescents with active RRP, 2) children with active RRP, 3) RRP patients who had undergone HPV vaccination prior to enrollment and, 4) people with RRP who were in remission. Anti-HPV6 and HPV11 serology was determined by cLIA on a single blood draw. RESULTS: Of the 70 subjects enrolled, 36, 16, 8, and 10, were in groups 1, 2, 3, and 4, respectively. 47% of participants aged >11 years and 81% aged ≤11 years possessed no antibodies against HPV6 or HPV11 (ie. double seronegative). 61% of patients in remission were double seronegative. All participants who had received HPV vaccine previously were seropositive to at least one of these low risk HPV types (ie none of them were double seronegative). Among patients who had active RRP and never had HPV vaccination (n = 52) there was an association between duration of symptoms and seropositivity. Of those who were seropositive, the geometric mean duration of symptoms was 11 years compared to 4.7 years for those who were seronegative (p = 0.001). CONCLUSION: People with RRP are capable of developing a humoral response to HPV6 and HPV11. That response appears to be robust when initiated by the HPV vaccine, but either nonexistent or slow to develop in response to infection. Most in remission do not have demonstrable antibody levels against HPV6 or HPV11.


Assuntos
Papillomavirus Humano 11/imunologia , Papillomavirus Humano 6/imunologia , Infecções por Papillomavirus/patologia , Infecções Respiratórias/patologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Infecções Respiratórias/imunologia , 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
20.
Cancer ; 126(8): 1656-1667, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32037524

RESUMO

BACKGROUND: Human papillomavirus (HPV)-related disease remains a significant source of morbidity and mortality, and this underscores the need to increase HPV vaccination to reduce the burden of the disease. The objective of this study was to examine the association between the number of HPV vaccine doses and the risk of histologically confirmed preinvasive cervical disease and high-grade cytology. METHODS: This retrospective matched cohort study used administrative data from Optum's Clinformatics DataMart Database to identify females aged 9 to 26 years who received 1 or more quadrivalent HPV vaccine doses between January 2006 and June 2015. Cases and controls were matched on region, age, sexually transmitted disease history, and pregnancy. All had a Papanicolaou test ≥1 year after the date of the matched case's final dose. Cox proportional hazards models were used to examine the association between the number of HPV vaccine doses and the incidence of preinvasive cervical disease and high-grade cytology. The Kaplan-Meier method was used to estimate the cumulative incidence rate at the 5-year follow-up. RESULTS: The study included 133,082 females (66,541 vaccinated and 66,541 unvaccinated) stratified by the number of HPV vaccine doses and the vaccine initiation age. Among those aged 15 to 19 years, the hazard ratio (HR) for high-grade cytology for the 3-dose group was 0.84 (95% confidence interval [CI], 0.73-0.97), whereas the HRs for histologically confirmed preinvasive cervical disease for 1, 2, and 3 doses were 0.64 (95% CI, 0.47-0.88), 0.72 (95% CI, 0.54-0.95), and 0.66 (95% CI, 0.55-0.80), respectively. CONCLUSIONS: The receipt of 1, 2, or 3 doses of an HPV vaccine by females aged 15 to 19 years was associated with a lower incidence of preinvasive cervical disease in comparison with unvaccinated females, and this supports the use of any HPV vaccination in reducing the burden of the disease.


Assuntos
Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/imunologia , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/imunologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Criança , Gerenciamento de Dados , Feminino , Humanos , Estudos Retrospectivos , Estados Unidos , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação/métodos , Adulto Jovem
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