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1.
Int J Cancer ; 146(6): 1667-1673, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31325316

RESUMO

Cervical cancer remains a significant cause of morbidity and mortality in women worldwide and is the leading cause of cancer-related death in Botswana. It is well established that women with HIV have a higher risk of persistent HPV infection leading to cervical cancer. We assessed HPV prevalence and genotype distribution in 126 tissue specimens from confirmed invasive cervical cancer cases using Abbott real-time PCR assay. Overall, 88 (69.8%) women were HIV-infected. Fifty-seven (64.8%) of the HIV-infected women had a baseline CD4+ count ≥350 cells/µl, and 82 (93.2%) were on antiretroviral therapy at the time of cervical cancer diagnosis. The median age of HIV-infected patients was significantly younger than that of HIV-uninfected patients (p < 0.001). HPV DNA was detected in all of 126 (100%) of tissues analyzed in our study. The HPV genotypes identified included the HPV-16 (75.4%), HPV-18 (28.6%) and other high-risk (hr) HPV genotypes (16.7%). HIV infection was positively associated with the presence of the HPV-16 genotype (p = 0.036), but not with HPV-18 or with other high-risk (hr)-HPV genotypes. Thirty-three percent of the patients had multiple hr-HPV genotypes, with higher rates in HIV-infected women. These results highlight the importance and potential impact of large-scale HPV vaccination programs covering HPV-16 and HPV-18 genotypes in countries like Botswana with high burden of HIV infection.


Assuntos
Infecções por HIV/virologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Fármacos Anti-HIV/uso terapêutico , Botsuana/epidemiologia , Colo do Útero/patologia , Colo do Útero/virologia , Efeitos Psicossociais da Doença , Estudos Transversais , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Genótipo , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Prevalência , Estudos Retrospectivos , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Vacinação
2.
BMC Infect Dis ; 19(1): 962, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711435

RESUMO

BACKGROUND: High-risk human papillomavirus (HR-HPV) testing is more sensitive than cytology for the detection of cervical cancer and its precursors. However, limited and inconsistent data are available about the efficacy of the combination of these two methods for screening cervical adenocarcinoma. This multicenter retrospective study investigated the screening results of a cohort of Chinese patients who were subsequently diagnosed with invasive cervical adenocarcinoma, with the goal of identifying the optimal cervical adenocarcinoma screening method. METHODS: We retrospectively retrieved and analyzed the data from patients with histologically confirmed primary invasive cervical adenocarcinoma from eight local pathology laboratories operated by KingMed Diagnostics, the largest independent operator of pathology laboratories in China, over a 2-year period. Only patients who underwent cytology and/or HR-HPV testing within 6 months before the adenocarcinoma diagnosis were included. HR-HPV DNA was detected using one of two HPV test kits: the Hybrid Capture 2 (HC2) assay (Qiagen, Hilden, Germany) and an HPV genotyping panel (Yaneng Bio, Shenzhen, China). RESULTS: Of the 311 patients, 136 underwent cytology alone, 106 underwent HR-HPV testing alone, and 69 underwent cytology and HR-HPV co-testing. The sensitivities of cytology alone (64.0, 95% confidence interval [CI]: 55.9-72.0) and HR-HPV testing alone (66.0, 95% CI: 57.0-75.1) were similar (P = 0.738). The sensitivity of cytology and HR-HPV co-testing (87.0, 95% CI: 79.0-94.9) was significantly higher than that of either cytology (P = 0.001) or HR-HPV testing alone (P = 0.002). CONCLUSIONS: Both cytology alone and HR-HPV testing alone showed poor screening efficiency, whereas the combination of the two clearly increased the efficiency of primary cervical adenocarcinoma screening. Thus, cytology and HR-HPV co-testing might be the most efficient cervical adenocarcinoma screening method.


Assuntos
Adenocarcinoma/diagnóstico , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colo do Útero/patologia , Colo do Útero/virologia , China , Feminino , Humanos , Laboratórios , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
3.
Virol J ; 16(1): 116, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590680

RESUMO

BACKGROUND: Finding new biomarkers for the early detection of cervical cancer is an essential requirement in this field. In this study, we aimed to evaluate the expression level of potential biomarkers in progression of cervical cancer in patients with cervical cancer compared to normal subjects. METHODS: The expression levels of tissue and serum miRNAs, including miR-9, miR-192 and miR-205, were investigated in 36 normal, 18 precancer, and 18 cervical cancer samples using real-time polymerase chain reaction. RESULTS: The results showed the higher significant expressions of miR-9, miR-192 and miR-205 in the tissue of cancer samples than those in the normal samples. Moreover, the miR-192 and miR-205 expression were significantly increased in the cancer group in comparison with the precancer group. Examination of serum samples revealed the increase in the expression level in the cancer groups than in the normal samples, for miR-9, miR-192 and miR-205 and the expressions of miR-9, miR-192 and miR-205 were significantly up-regulated in the precancer group in comparison with the normal group. Also the expression of miR-205 was remarkably increased in the cancer group in comparison with the precancer group. The receiver operating characteristic (ROC) analyses showed the highest area under the curve value for miR-192. CONCLUSIONS: Given the increased expression level of miR-192 in cancer and in precancerous tissue and serum compared with the normal tissue and serum validated by analysing the ROC curve, miR-192 can be used as potential biomarker for the early detection of cervical cancer.


Assuntos
Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer , MicroRNAs/sangue , MicroRNAs/genética , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Casos e Controles , Colo do Útero/patologia , Colo do Útero/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Curva ROC , Regulação para Cima , Adulto Jovem
4.
Nat Commun ; 10(1): 4739, 2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31628331

RESUMO

HIV viral reservoirs are established very early during infection. Resident memory T cells (TRM) are present in tissues such as the lower female genital tract, but the contribution of this subset of cells to the pathogenesis and persistence of HIV remains unclear. Here, we show that cervical CD4+TRM display a unique repertoire of clusters of differentiation, with enrichment of several molecules associated with HIV infection susceptibility, longevity and self-renewing capacities. These protein profiles are enriched in a fraction of CD4+TRM expressing CD32. Cervical explant models show that CD4+TRM preferentially support HIV infection and harbor more viral DNA and protein than non-TRM. Importantly, cervical tissue from ART-suppressed HIV+ women contain high levels of viral DNA and RNA, being the TRM fraction the principal contributor. These results recognize the lower female genital tract as an HIV sanctuary and identify CD4+TRM as primary targets of HIV infection and viral persistence. Thus, strategies towards an HIV cure will need to consider TRM phenotypes, which are widely distributed in tissues.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Memória Imunológica/imunologia , Adulto , Idoso , Antirretrovirais/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/virologia , Colo do Útero/efeitos dos fármacos , Colo do Útero/virologia , Reservatórios de Doenças/virologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Pessoa de Meia-Idade , Membrana Mucosa/efeitos dos fármacos , Membrana Mucosa/virologia , Carga Viral/efeitos dos fármacos , Carga Viral/genética , Carga Viral/imunologia
5.
BMC Cancer ; 19(1): 986, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646977

RESUMO

BACKGROUND: To examine differences in the plasma levels of miRNA-21, - 214, -34a, and -200a in patients with persistent high-risk human papillomavirus (hr-HPV) infection or with cervical lesions of different grades. METHODS: Venous blood was collected from 232 individuals to measure the plasma expression levels of miRNA-21, - 214, -34a, and -200a. The subjects included normal controls and patients with persistent hr-HPV infection, CIN1, CIN2, CIN3, or cervical cancer (n = 42, 31, 19, 54, 71, and 15 patients, respectively). Cervical conization specimens were collected from all the women. To ensure the accuracy of histopathology, three consecutive tissue sections with an identical diagnosis were selected, and dissection samples were taken from them for miRNA detection. Eligible cases met the inclusion criteria based on sample observation using the middle slice of sandwich tissue sections from the pathological tissue in accordance with the diagnosis of CIN1, CIN2 and CIN3 in 8, 29, and 26 cases, respectively. The miRNA-21, - 214, -34a, and -200a expression levels in the paraffin-embedded tissue samples were determined. The percentage of patients with a CIN2+ diagnosis at 30-49 years old was significantly different from that of those diagnosed with CIN1. The incidence of CIN2+ patients exposed to passive smoking was significantly different from that of CIN1- patients. The percentage of CIN2+ patients with three pregnancies was significantly different from that of those with CIN1, and the percentage of CIN2+ subjects with ≥4 pregnancies was significantly different from that of CIN1- patients. The number of CIN2+ patients with two or more induced abortions was significantly different from that of patients with CIN1. The percentage of CIN2+ patients who underwent a caesarean section was significantly different from that of patients with CIN. The percentage of CIN2+ patients with first-degree relatives with cancer was significantly different from that of those with CIN1. Among CIN2+ patients, the percentage with a first sexual encounter at ≤20 years old was significantly different from that of those with CIN1. The percentage of CIN2+ patients with ≥2 sexual partners was significantly different from that of CIN1- patients. RESULTS: The plasma miRNA-214, -34a, and -200a expression levels were decreased in patients with more severe cervical lesions. Plasma miRNA levels in CIN1- patients were significantly different from those in CIN2+ patients. The kappa values for miRNA-21, - 214, -34a and -200a in tissue versus plasma were 0.7122, 0.9998, 0.8986 and 0.7458, respectively. The sensitivity of each biomarker for detecting CIN2 was calculated, and ROC curves of the four miRNA biomarkers were drawn. The AUC of the four plasma miRNAs was greater than 0.5, with the AUC of miRNA-21 being the largest at 0.703. The plasma miRNA expression levels exhibited at least one tie between CIN1 and CIN2. The AUCs for miRNA-21, -34a, -200a and - 214 were 0.613, 0.508, 0.615 and 0.505, respectively. CONCLUSIONS: Changes in plasma miRNA-21, - 214, -34a and -200a levels were associated with cervical lesion severity. The plasma miRNA levels in CIN1- subjects were significantly different from those in CIN2+ subjects. This analysis may help in detection of high-grade cervical lesions.


Assuntos
Regulação da Expressão Gênica , MicroRNAs/sangue , MicroRNAs/genética , Infecções por Papillomavirus/sangue , Doenças do Colo do Útero/sangue , Adulto , Área Sob a Curva , Neoplasia Intraepitelial Cervical/sangue , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/metabolismo , Colo do Útero/patologia , Colo do Útero/virologia , Feminino , Humanos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Infecções por Papillomavirus/patologia , Curva ROC , Fatores de Risco , Doenças do Colo do Útero/patologia , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/patologia
6.
Virol J ; 16(1): 114, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31511025

RESUMO

BACKGROUND: Human papillomavirus type-6 (HPV6) is the major etiological agent of anogenital warts both men and women. The present study aimed to characterize the genetic diversity among HPV6 in Southwest China, and to investigate the origin of, selective pressure experienced by, and impact of the resultantly identified genetic variants on the HPV6 secondary structure. METHODS: Phylogenetic trees were constructed by Maximum-likelihood and the Kimura 2-parameters methods by Molecular Evolutionary Genetics Analysis version 6.0. The diversity of secondary structure was analyzed by PSIPred software. The selection pressures acting on the E6/E7 genes were estimated by Phylogenetic Analyses by Maximum Likelihood version 4.8 software. RESULTS: HPV6 was the most prevalent low risk HPV type in southwest China. In total, 143 E6 and E7 gene sequences of HPV6 isolated from patients were sequenced and compared to GenBank HPV6 reference sequence X00203. The results of these analyses revealed that both the HPV6 E6 and E7 were highly conserved within the analyzed patient samples, and comprised only 3 types of variant sequence, respectively. Furthermore, the analysis of HPV6 E6 and E7 sequences revealed seven/five single-nucleotide mutations, two/four and five/one of which were non-synonymous and synonymous, respectively. The phylogenetic analyses of the E6 and E7 sequences indicated that they belonged to sub-lineage A1 and sub-lineage B1, whereas the selective pressure analyses showed that only the E7 mutation sites 4R, 34E, and 52F were positive selection. CONCLUSIONS: HPV6 (detection rate = 13.10%) was very prevalent in southwest China, both the HPV6 E6 and E7 sequences were highly conserved within the analyzed patient samples in southwest China, indicating that the low risk HPV6 can adapt to the environment well without much evolution.


Assuntos
Papillomavirus Humano 6/genética , Proteínas Oncogênicas Virais/genética , Polimorfismo de Nucleotídeo Único , Adulto , Colo do Útero/virologia , China , Estudos Transversais , Feminino , Humanos , Proteínas Oncogênicas Virais/química , Infecções por Papillomavirus/virologia , Filogenia , Análise de Sequência de DNA , Adulto Jovem
7.
Biomed Pharmacother ; 118: 109359, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545243

RESUMO

As one of the highly contagious forms, herpes simplex virus type 2 (HSV-2) commonly caused severe genital diseases and closely referred to the HIV infection. The lack of effective vaccines and drug-resistance proclaimed the preoccupation for alternative antiviral agents against HSV-2. Molecules bearing indole nucleus presented diverse biological properties involving antiviral and anti-inflammatory activities. In this study, one of the indole molecules, arbidol derivative (ARD) was designed and synthesized prior to the evaluation of its anti-HSV-2 activity. Our data showed that the ARD effectively suppressed HSV-2-induced cytopathic effects and the generation of progeny virus, with 50% effective concentrations of 3.386 and 1.717 µg/mL, respectively. The results of the time-course assay suggested that the ARD operated in a dual antiviral way by interfering virus entry and impairing the earlier period of viral cycle during viral DNA synthesis. The ARD-mediated HSV-2 inhibition was partially attained by blocking NF-κB pathways and down-regulating the expressions of several inflammatory cytokines. Furthermore, in vivo studies showed that oral administration of ARD protected BALB/c mice from intravaginal HSV-2 challenge by alleviating serious vulval lesions and histopathological changes in the target organs. Besides, the treatment with ARD also made the levels of viral protein, NF-κB protein and inflammatory cytokines lower, in consistent with the in-vitro studies. Collectively, ARD unveiled therapeutic potential for the prevention and treatment of HSV-2 infections.


Assuntos
Colo do Útero/patologia , Colo do Útero/virologia , Células Epiteliais/virologia , Herpesvirus Humano 2/efeitos dos fármacos , Indóis/farmacologia , Animais , Antivirais/química , Antivirais/farmacologia , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Humanos , Indóis/química , Indóis/toxicidade , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Receptores Toll-Like/metabolismo , Vagina/efeitos dos fármacos , Vagina/patologia , Vagina/virologia , Replicação Viral/efeitos dos fármacos
8.
Nat Commun ; 10(1): 3753, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434895

RESUMO

Semen is the vehicle for virion dissemination in the female reproductive tract (FRT) in male-to-female HIV transmission. Recent data suggests that higher frequency semen exposure is associated with activation of anti-HIV mechanisms in HIV negative sex workers. Here, we use a non-human primate (NHP) model to show that repeated vaginal exposure to semen significantly reduces subsequent infection by repeated low-dose vaginal SIVmac251 challenge. Repeated semen exposures result in lower CCR5 expression in circulating CD4+ T-cells, as well as higher expression of Mx1 (in correlation with IFNε expression) and FoxP3 in the cervicovaginal mucosa, and increased infiltration of CD4+ T-cells. Establishing in vivo evidence of competing effects of semen on transmission impacts our basic understanding of what factors may determine HIV infectivity in humans. Our results clearly indicate that repeated semen exposure can profoundly modulate the FRT microenvironment, paradoxically promoting host resistance against HIV acquisition.


Assuntos
Colo do Útero/imunologia , Membrana Mucosa/imunologia , Sêmen/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/imunologia , Vagina/imunologia , Animais , Linfócitos T CD4-Positivos , Colo do Útero/virologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Fatores de Transcrição Forkhead/metabolismo , Infecções por HIV/imunologia , Infecções por HIV/transmissão , Humanos , Macaca mulatta , Membrana Mucosa/metabolismo , Proteínas de Resistência a Myxovirus/metabolismo , Receptores CCR5/metabolismo , Vagina/virologia
9.
BMC Infect Dis ; 19(1): 740, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438877

RESUMO

BACKGROUND: Women living with HIV (WLWH) have high rates of persistent high-risk human papillomavirus (hrHPV) infections and cervical cancer. We aimed to assess the distribution of hrHPV genotypes, risk factors of type-specific hrHPV persistence, and high-grade squamous intraepithelial lesions or worse (≥HSIL) in WLWH in Denmark. METHODS: From the prospective Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) we identified WLWH with a positive hrHPV test during the study period; 2011-2014. HIV demographics were retrieved from the Danish HIV Cohort Study and pathology results from the The Danish Pathology Data Bank. Logistic regression was used to identify risk factors associated with persistent hrHPV infection (positivity of the same hrHPV type in two samples one-two years after the first hrHPV positive date) and ≥ HSIL. RESULTS: Of 71 WLWH, 31 (43.7%) had persistent hrHPV infection. Predominant hrHPV genotypes were HPV58, 52, 51, and 35 and most frequently observed persistent genotypes were HPV52, 33 and 31. CD4 < 350 cells/µL predicted genotype-specific hrHPV persistence (adjusted OR 4.36 (95%CI: 1.18-16.04)) and ≥ HSIL was predicted by prior AIDS (adjusted OR 8.55 (95% CI 1.21-60.28)). CONCLUSIONS: This prospective cohort study of well-treated WLWH in Denmark found a high rate of persistent hrHPV infections with predominantly non-16/18 hrHPV genotypes. CD4 count < 350 cells/µL predicted hrHPV persistence, while prior AIDS predicted ≥HSIL.


Assuntos
Colo do Útero/virologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Adulto , Contagem de Linfócito CD4 , Colo do Útero/patologia , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Genótipo , HIV , Infecções por HIV/virologia , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Sistema de Registros , Fatores de Risco , Lesões Intraepiteliais Escamosas Cervicais/complicações , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/epidemiologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia
10.
Virol J ; 16(1): 107, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438976

RESUMO

BACKGROUND: The indicating FTA card is a dry medium used for collection of cervical samples. HPVIR is a multiplex real-time PCR test that detects 12 high-risk human papillomavirus types (hrHPV) and provides single genotype information for HPV16, - 31, - 35, - 39, - 51, - 56, and - 59 and pooled type information for HPV18/45 and HPV33/52/58. The aim of this study was to evaluate whether a strategy with cervical samples collected on the FTA card and subsequently analysed with the HPVIR test complies with the criteria of the international guidelines for a clinically validated method for cervical screening. METHODS: We performed a non-inferiority test comparing the clinical sensitivity and specificity of the candidate test (FTA card and HPVIR) with a clinically validated reference test (Cobas® HPV test) based on liquid-based cytology (LBC) samples. Two clinical samples (LBC and FTA) were collected from 896 participants in population-based screening. For evaluation of the specificity we used 799 women without ≥ CIN2, and for clinical sensitivity we used 67 women with histologically confirmed ≥ CIN2. The reproducibility was studied by performing inter- and intra-laboratory tests of 558 additional clinical samples. RESULTS: The clinical sensitivity and specificity for samples collected on the FTA card and analysed using the HPVIR test were non-inferior to samples analysed with the Cobas® HPV test based on LBC samples (non-inferiority test score, p = 1.0 × 10- 2 and p = 1.89 × 10- 9, respectively). Adequate agreement of > 87% was seen in both the intra- and inter-laboratory comparisons. CONCLUSIONS: Samples collected on the indicating FTA card and analysed with HPVIR test fulfil the requirements of the international guidelines and can therefore be used in primary cervical cancer screening.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Detecção Precoce de Câncer/normas , Testes de DNA para Papilomavírus Humano/normas , Programas de Rastreamento/normas , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Alphapapillomavirus/classificação , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/virologia , DNA Viral/genética , Feminino , Genótipo , Testes de DNA para Papilomavírus Humano/instrumentação , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Guias de Prática Clínica como Assunto , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Manejo de Espécimes/instrumentação , Manejo de Espécimes/métodos , Neoplasias do Colo do Útero/virologia
11.
Intervirology ; 62(2): 90-95, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31412350

RESUMO

BACKGROUND/AIMS: In Zimbabwe, cervical cancer is screened through cytology and visual inspection with acetic acid and cervicography (VIAC). The effectiveness of these methods can be increased if complemented by a human papillomavirus DNA detection tool since most cervical cancer cases are caused by persistent infection with high-risk human papillomavirus (HR-HPV) genotypes. Moreover, the possibility of multiple-genotype HR-HPV infections warrants the need for HPV detection tools with the capacity to detect both single and multiple infections. The aim of this study was to detect HR-HPV genotypes (HPV 16, 18, 31, 33, 35, 45, 51, 52, 56, and 58), using multiplex polymerase chain reaction (PCR), in stored cervicovaginal swabs from both HIV-positive and HIV-negative women reporting for routine cervical cancer screening. METHODOLOGY: Stored cervicovaginal swabs from sexually active women who underwent VIAC at the Parirenyatwa Referral Hospital in Harare, Zimbabwe, between February and April 2015 and had received HIV counselling and testing were genotyped for the selected 10 HR-HPV genotypes using in-house multiplex PCR. The results from the multiplex PCR were compared to those previously obtained when the same samples were HPV genotyped with next-generation sequencing (NGS) on an MiSeq platform (Illumina; USA). RESULTS: A total of 136 women were recruited and all 10 HR-HPV genotypes were detected. Quality control failed in 3 of the 136 swabs during the multiplex PCR reactions. The prevalence of HR-HPV genotypes in the study subjects was 53% (70/133). HIV-infected women were 1.67 times more likely to be infected with HR-HPV than were HIV-negative women (OR 1.67; p = 0.17). Of the 70 HR-HPV-positive cases, 37% (26/70) had multiple HR-HPV infections, and the majority of them were HIV infected. HIV-infected women were 1.86 times more likely to have multiple HR-HPV infections than HIV-negative women (OR 1.86; p = 0.20). Multiplex PCR and NGS had an almost perfect concordance rate in -HR-HPV detection (κ = 0.960), with only 3 discordant cases (negative with NGS and positive for HPV16 with multiplex PCR). CONCLUSION: Multiplex PCR can detect HR-HPV genotypes that are common in Zimbabwe and could be used to detect HR-HPV genotypes from women attending cervical cancer screening programs at the Parirenyatwa VIAC clinic in Harare.


Assuntos
Detecção Precoce de Câncer/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colo do Útero/virologia , Estudos Transversais , DNA Viral/genética , Feminino , Genótipo , Infecções por HIV/virologia , Papillomavirus Humano 16/genética , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Infecções por Papillomavirus/virologia , Fatores de Risco , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Zimbábue
13.
BMC Womens Health ; 19(1): 103, 2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340789

RESUMO

BACKGROUND: Probiotics has been shown to be effective in reducing vaginal colonization of pathogenic organisms. The aim of this study was to investigate the influence of probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on genital high-risk human papilloma virus (HR-HPV) clearance and quality of cervical smear. METHODS: This was a randomized, double-blinded, placebo-controlled trial. Women with genital HR-HPV infection were randomized into study and control groups. A probiotic or placebo preparation was administered orally (one capsule daily) until negative HR-HPV testing. A cervical smear and HR-HPV tests were performed at the beginning of the study and every 3 months thereafter until a negative result was obtained. RESULTS: A total of 121 women with genital HR-HPV infection were enrolled (62 in the study group and 59 in the control group). There was no significant difference in HR-HPV clearance rate between the two groups (58.1% vs. 54.2%). The only factor predicting HR-HPV clearance was a lower initial viral load (HR 3.214; 95% CI: 1.398, 7.392; p = 0.006). Twenty-two women had a mildly abnormal initial cervical smear and nine had an unsatisfactory smear. At 6 months follow-up, both mildly abnormal cervical smear and unsatisfactory smear rates had decreased significantly in the study group compared to the control group (p = 0.017 and 0.027). CONCLUSIONS: The application of probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 did not influence genital HR-HPV clearance, but may have decreased the rates of mildly abnormal and unsatisfactory cervical smears. TRIAL REGISTRATION: Clinicaltrials.gov NCT01599416 , May, 2012. Retrospectively registered.


Assuntos
Colo do Útero/patologia , Colo do Útero/virologia , Papillomaviridae , Infecções por Papillomavirus/terapia , Probióticos/uso terapêutico , Vagina/virologia , Adulto , Método Duplo-Cego , Feminino , Genótipo , Humanos , Lactobacillus reuteri , Lactobacillus rhamnosus , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Esfregaço Vaginal , Carga Viral
14.
Virol J ; 16(1): 92, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337408

RESUMO

BACKGROUND: HPV DNA Array is an E1-targeting PCR genotyping test, with capability of distinguishing 18 high-risk (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) and 11 low-risk HPV types (6, 11, 40, 42, 44, 54, 67, 69, 70, 85, 97). HPV DNA Array uses multiplex PCR for E1-gene sequence amplification. The amplicons are detected and genotyped by reverse hybridization to immobilized DNA probes spotted as triplets in single 96 well-plate wells and read by AID ELISPOT reader. METHODS: Aim of the study was to evaluate the clinical performance of the assay against internationally accepted and FDA approved Cobas 4800 HPV test (Roche Diagnostics). Study population comprised of 500 cervical samples. RESULTS: HPV DNA Array demonstrated a very high sensitivity of 100% for CIN2+ and 100% for CIN3+ detection, same as Cobas 4800. HPV DNA Array showed greater sensitivity for CIN2+ detection than cytology (100% vs. 13.6%). The agreement to Cobas 4800 for HPV detection, irrespective of type, was 81.4% with κ = 0.613. The agreement for HPV 16 was 92.8% (κ = 0.929), and for HPV 18 54.2% (κ = 0.681). CONCLUSION: HPV DNA Array demonstrated good clinical performance for detection of high-grade lesions, and may be considered for usage in a screening setting.


Assuntos
DNA Viral/genética , Técnicas de Genotipagem/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Adulto , Idoso , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/patologia , Colo do Útero/virologia , Técnicas Citológicas , Detecção Precoce de Câncer , Feminino , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Infecções por Papillomavirus/virologia , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem
15.
Int J Med Sci ; 16(7): 1042-1049, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341418

RESUMO

Human papillomavirus type 16 (HPV16) is a high-risk HPV type and a potent carcinogen. HPV E1 is one of the most highly conserved proteins and it plays a central role in initiating HPV DNA replication. In current study, we enrolled 161 HPV16-positive cervical cancer patients (case group) and 171 HPV16-positive asymptomatic individuals (control group) in a study to analyse the association between HPV16 E1 genetic mutations and cervical cancer. The samples of case group were cervical cancer tissues and the samples of control group were cervical exfoliated cells. Three variants (A4, A1-A3 and D3) were found in the case group, 68.3% of the HPV16 E1 sequences belonged to the A4 (As) sub-lineage, 29.2% belonged to the A1-A3 (EUR) sub-lineage, and 2.5% belonged to the D3 (AA1) sub-lineage. Two variants (A4 and A1-A3) occurred in the control group. The A4 (As) sub-lineage was predominant in this group as well (66.1%), followed by the A1-A3 (EUR) sub-lineage (33.9%), but the D3 (AA1) sub-lineage was not found in the control group. The distribution of the HPV16 variants between the case and control groups was significantly different (P<0.05). When the distribution of the HPV16 E1 gene mutations was compared, the distribution of twenty-seven mutations was significantly different between the case and control groups (P<0.05), and twenty-two mutations occurred only in the D3 (AA1) sub-lineage, two were found only in the A4 (As) sub-lineage, one was found in the A1-A3 (EUR) sub-lineage, two was found in both the A4 (As) and A1-A3 (EUR) sub-lineages. In the sub-lineage analysis, the differences in the T933A (A23A), T1014G (D50E) and G2160A (R432R) mutations were statistically significant between the case and control groups for the A4 (As) sub-lineage (P<0.05), and the differences in the T2232C (F456F), G2337A (M491I) and A2547G (P561P) mutations were statistically significant between the case and control groups for the A1-A3 (EUR) sub-lineage (P<0.05). In the current study, we describe specific mutations in the HPV16 E1 gene associated with cervical cancer, and our study will provide a good reference for further functional studies of the relationship between cervical cancer carcinogenesis and HPV genes.


Assuntos
Papillomavirus Humano 16/genética , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Substituição de Aminoácidos , Grupo com Ancestrais do Continente Asiático , Carcinogênese , Estudos de Casos e Controles , Colo do Útero/patologia , Colo do Útero/virologia , DNA Viral/genética , Feminino , Genoma Viral/genética , Genótipo , Papillomavirus Humano 16/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Mutação , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia
16.
Przegl Epidemiol ; 73(1): 31-37, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31134772

RESUMO

INTRODUCTION: The human papilloma virus (HPV) belongs to double-stranded, DNA circular viruses which infect the epithelial cells. The highest incidence of HPV is identified in malignant processes which affect the uterine cervix, as well as vulvar, penile, rectal and pharyngeal regions. GOAL OF STUDY: An attempt to find correlations between HPV incidence rates in urine sediment cells and in desquamated epithelial cells of the uterine cervix in a group of patients with frequent, recurrent cystitis. MATERIALS AND METHODS: HPV presence was studied, both in urine sediment cells and in uterine cervix epithelial cells of 77 patients. RESULTS: An analysis of urinary sediments brought a total of twenty (25.97%) positive and 57 (74.03%) negative results. In turn, an evaluation of uterine cervix material samples revealed 17 (22.08%) positive and 60 (77.92%) negative results. CONCLUSIONS: The study enabled a comparison between HPV prevalence rates in urine sediment cells and in uterine cervix epithelial cells of an examined patient. The performed observations are likely to trigger a further analysis of the studied issue; however, the obtained results provide arguments for different natural histories of the infection processes.


Assuntos
Colo do Útero/virologia , Cistite/virologia , Genoma Viral , Genótipo , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Adulto , Idoso , Cistite/complicações , DNA Viral , Células Epiteliais/virologia , Feminino , Técnicas de Genotipagem , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Polônia
17.
J Acquir Immune Defic Syndr ; 81(2): 163-165, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31095006

RESUMO

BACKGROUND: Progestin contraception has been linked to higher risk of female to male sexual HIV transmission. SETTING: A clinical trial among HIV-infected women in Lilongwe, Malawi, randomized to initiation of depomedroxyprogesterone acetate injectable or levonorgestrel implant, and followed for up to 33 months, with the outcome of HIV shedding in the genital tract. METHODS: We compared the frequency and magnitude of HIV genital shedding before and after initiation of contraception and between study arms among women receiving antiretroviral therapy (ART). Genital HIV RNA was measured in TearFlo Strips using the Abbott RealTime HIV-1 assay. RESULTS: Among 68 HIV-infected Malawian women on ART, randomization to depot medroxyprogesterone acetate compared with the levonorgestrel implant was not associated with genital shedding and neither progestin contraceptive was associated with increased HIV genital shedding, for up to 33 months after contraceptive initiation. Having detectable plasma HIV [adjusted risk ratio (RR) 10.5; 95% confidence interval (CI): 3.18 to 34.7] and detectable genital shedding before contraceptive initiation (adjusted RR 3.53; 95% CI: 1.31 to 9.47) were associated with a higher risk of detectable genital shedding after contraceptive initiation. Higher plasma efavirenz concentrations were associated with a lower risk of detectable genital shedding (adjusted RR 0.85; 95% CI: 0.73 to 0.99, per increase of 1000 ng/mL). CONCLUSION: Among HIV-infected women receiving ART, our results provide evidence that progestin contraception does not impact women's risk of transmission of HIV to partners. Our finding that detectable genital shedding before contraceptive initiation independently predicts shedding suggests that there may be other individual-level biological or behavioral factors that increase the risk for shedding.


Assuntos
Antirretrovirais/uso terapêutico , Anticoncepção , Infecções por HIV/tratamento farmacológico , Progestinas , Eliminação de Partículas Virais/efeitos dos fármacos , Adulto , Antirretrovirais/farmacologia , Benzoxazinas/sangue , Benzoxazinas/farmacologia , Colo do Útero/virologia , Anticoncepcionais Femininos/farmacologia , Implantes de Medicamento , Feminino , Seguimentos , Genitália Feminina , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Levanogestrel/farmacologia , Levanogestrel/uso terapêutico , Malaui , Acetato de Medroxiprogesterona/farmacologia , Acetato de Medroxiprogesterona/uso terapêutico , Resultado do Tratamento
18.
Virol J ; 16(1): 67, 2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109361

RESUMO

BACKGROUND: Human papillomavirus (HPV) infection may lead to a series of lesions in the cervix. Distributions of HPV genotypes reveal that an increased prevalence of high-risk HPV (HR-HPV) is positively correlated with the severity of cervical lesions. Furthermore, persistent infection of HR-HPV is associated with a risk of cervical cancer. Considering the newly approval of the HPV vaccine in China and the prevalence of HPV distribution, which is meaningful for directing efforts for HPV vaccination, a more detailed understanding of HPV distribution is critical. This study aimed to investigate the overall prevalence of HPV and the age-specific features related to HPV distribution in the Jiangsu population. METHODS: We collected a total of 62,317 cervical cytological specimens from Xuzhou, Nanjing and Suzhou, which represent the northern, middle and southern regions of Jiangsu Province, respectively. All these samples were assigned to 6 groups based on participant age. HPV genotypes tests were performed by using a commercial kit which is designed for the detection of 17 high-risk HPV genotypes and 6 low-risk HPV genotypes. RESULTS: The overall prevalence of HPV was up to 26.92% in Jiangsu Province. The most common high-risk genotype was HPV52 (5.09%), followed by HPV16, HPV58, HPV53, HPV51 and HPV68. The most prevalent low-risk genotype was HPV81 (2.70%), followed by HPV43, HPV42, HPV6, HPV11 and HPV83. Most infections were caused by HR-HPV, while single-genotype infection occurred more frequently than multiple-genotype infection. Regarding participant age, the overall infection rate of HPV was distributed in a U-shaped manner, with the highest peak in the younger than 20-year-old cohort. Additionally, significant variations were found between different cities, representing different regions of Jiangsu. CONCLUSIONS: HPV prevalence is high in Jiangsu Province. The prevention of HPV-related diseases is challenging. Given the variation in HPV prevalence between ages groups and regions, a flexible HPV vaccination program, adjusted base on regional infection features, could have a beneficial effect in Jiangsu Province.


Assuntos
Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasia Intraepitelial Cervical/epidemiologia , China/epidemiologia , DNA Viral/genética , Detecção Precoce de Câncer , Feminino , Genótipo , Papillomavirus Humano 11/genética , Papillomavirus Humano 16/genética , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Prevalência , Neoplasias do Colo do Útero/epidemiologia , Adulto Jovem
19.
PLoS One ; 14(5): e0214152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31095572

RESUMO

Progestin-only long-acting reversible contraceptives (LARCs) are increasingly popular among women seeking contraception; however, recent epidemiological studies suggest that systemically administered medroxyprogesterone acetate (MPA) may increase HIV acquisition. In order to determine the exact mechanisms underlying increases in transmission specific to MPA use and to test safer, alternative contraceptive progestin types and delivery methods, in vitro modeling studies must be performed. To achieve this, it is imperative that accurate hormone concentrations be utilized when modeling progestin-mediated outcomes, as the down-stream effects are dose-dependent. The local concentrations of progestins to which the lower female genital tract tissues are exposed after initiation of LARCs are unknown, but they likely differ from peripheral concentrations, dependent upon the progestin type and delivery method. Here, we measured in vivo endocervical and plasma concentrations of (1) systemically-delivered depo MPA (DMPA), (2) levonorgestrel (LNG) delivered via intrauterine system (IUS) and (3) etonogestrel (ETG) delivered via vaginal ring in women who recently initiated contraception treatment. Levels of ETG and LNG in cervical secretions were 100-200 fold higher than plasma levels. In contrast, measurable MPA levels were approximately 10-fold higher in plasma compared to cervical secretions. These results will inform the design of accurate in vitro studies on the influence of progestins on epithelial cells, tissue explants, and peripheral blood cells, to be able to better predict in vivo outcomes. Subsequent observations will aid in determining how MPA might influence HIV acquisition and may facilitate identification of optimal progestin-containing LARC alternatives for women at high risk for HIV infection.


Assuntos
Anticoncepcionais Femininos/administração & dosagem , Infecções por HIV/prevenção & controle , Progestinas/administração & dosagem , Adolescente , Adulto , Colo do Útero/efeitos dos fármacos , Colo do Útero/virologia , Anticoncepção/efeitos adversos , Anticoncepcionais Femininos/efeitos adversos , Desogestrel/administração & dosagem , Feminino , Humanos , Levanogestrel/administração & dosagem , Acetato de Medroxiprogesterona/administração & dosagem , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-30949454

RESUMO

Aim: This study aimed to follow the impact of human papillomavirus (HPV) catch-up and vaccination on the very high cervical HPV-prevalence in women at a youth clinic in central Stockholm during the period 2008-2018. Background: 2008-2010, cervical HPV-prevalence (69.5%) and HPV16 prevalence (34.7%) were high in non-vaccinated women at a youth clinic in Stockholm. 2013-2015, after the introduction of the quadrivalent-Gardasil® HPV-vaccine, HPV16 and HPV6 prevalence had decreased. Here, cervical HPV-prevalence was investigated 10 years after primary sampling. Material and Methods: 2017-2018, 178 cervical swabs, from women aged 15-23 years old, were tested for 27 HPV types by a bead-based multiplex method. HPV-prevalence data were then related to vaccination status and age and compared to HPV-prevalence in 615 samples from 2008 to 2010 and 338 samples from 2013 to 2015 from the same clinic, and to HPV types in 143 cervical cancer cases during 2003-2008 in Stockholm. Results: The proportion of vaccinated women increased from 10.7% (2008-2010) to 82.1% (2017-2018). The prevalence of all 27 HPVs, all high-risk HPVs (HR-HPVs) and the combined presence of the quadrivalent-Gardasil® types HPV16, 18, 6, and 11, was lower in vaccinated compared to unvaccinated women (67.4 vs. 93.3%, p = 0.0031, 60.1 vs. 86.7%, p = 0.0057 and 5.8 vs. 26.7%, p = 0.002, respectively). Furthermore, HPV16 prevalence in non-vaccinated women 2017-2018 was lower than that in 2008-2010 (16.7 and 34.7%, respectively, p = 0.0471) and similar trends were observed for HPV18 and 11. In both vaccinated and non-vaccinated women, the most common non-quadrivalent-Gardasil® vaccine HR-HPV types were HPV39, 51, 52, 56, and 59. Together they accounted for around 9.8% of cervical cancer cases in Stockholm during 2003-2008, and their prevalence tended to have increased during 2017-2018 compared to 2008-2010. Conclusion: Quadrivalent-Gardasil® vaccination has decreased HPV-vaccine type prevalence significantly. However, non-vaccine HR-HPV types remain high in potentially high-risk women at a youth clinic in Stockholm.


Assuntos
Colo do Útero/virologia , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Adulto , Feminino , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Humanos , Epidemiologia Molecular , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Prevalência , Suécia/epidemiologia , Adulto Jovem
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