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1.
Medicine (Baltimore) ; 99(38): e22320, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957398

RESUMO

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


Assuntos
Detecção Precoce de Câncer/métodos , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Distribuição por Idade , China , Feminino , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Neoplasias do Colo do Útero/virologia
2.
J Exp Clin Cancer Res ; 39(1): 200, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967703

RESUMO

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


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Neoplasias de Cabeça e Pescoço/patologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Pneumonia Viral/complicações , Serina Endopeptidases/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estudos de Casos e Controles , Infecções por Coronavirus/virologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pandemias , Infecções por Papillomavirus/virologia , Pneumonia Viral/virologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Taxa de Sobrevida
3.
PLoS Pathog ; 16(8): e1008792, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32813746

RESUMO

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


Assuntos
Proteínas de Transporte/antagonistas & inibidores , Proliferação de Células , Queratinócitos/patologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/complicações , Proteínas Repressoras/metabolismo , Neoplasias Cutâneas/etiologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Células Cultivadas , Regulação para Baixo , Humanos , Queratinócitos/imunologia , Queratinócitos/virologia , Camundongos , Camundongos Transgênicos , Proteínas Oncogênicas Virais/genética , Papillomaviridae/isolamento & purificação , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/virologia , Proteínas Repressoras/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Proteína Supressora de Tumor p53/genética
4.
PLoS One ; 15(8): e0237988, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853216

RESUMO

OBJECTIVE: To evaluate the 9-year incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and cumulative adherence to perform a next test in a cohort of women aged 40+ years with no cervical screening cytology within a window of 5 years (underscreened women), after baseline cervical cytology and HPV tests. METHODS: In Catalonia, Spain, co-testing with cytology and HPV test has been recommended in the Public Health system since 2006 for underscreened women. In 2007, 1,594 women with underscreened criteria were identified and followed through medical records form Pathological Department. 9-year cumulative incidence of histologically confirmed CIN2+ and cumulative adherence to perform a next test were estimated using Kaplan-Meier statistics. RESULTS: Follow-up was available for 1,009 women (63.3%) resulting in 23 women with. CIN2+ (2.3%). Of them, 4 women (17%) had both tests negative at baseline (3CIN2 and 1CIN3) with cumulative incidence of CIN2+ of 0.4% (95% CI: 0.1-1.4) at 5-years and 1.3% (95% CI: 0.4-3.7) at 9-years. During the first year, the prevalence among women with both tests positive was 27.0% (95% CI: 13.0-50.6) for CIN2+. Lost to follow-up was higher among women with both tests negative compared to those with both positive tests (38.7% vs 4.2%, p-value <0.001). 40.5% of the women HPV-/cyto- had a re-screening test during the 4 years following the baseline, increasing until 53.5% during the 6 years of follow-up. CONCLUSIONS: HPV detection shows a high longitudinal predictive value at 9-year to identify women at risk to develop CIN2+. The data validate a safe extension of the 3-year screening intervals (current screening interval) to 5-year intervals in underscreened women that had negative HPV result at baseline. It is necessary to establish mechanisms to ensure screening participation and adequate follow-up for these women.


Assuntos
Programas de Rastreamento , Papillomaviridae/isolamento & purificação , Neoplasias do Colo do Útero/virologia , Idoso , Estudos de Coortes , Detecção Precoce de Câncer , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Papillomaviridae/fisiologia , Risco , Fatores de Tempo , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia
5.
Medicine (Baltimore) ; 99(27): e21005, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629719

RESUMO

INTRODUCTION: Mild local hyperthermia at 44°C has been proven efficacious in the treatment of cutaneous warts induced by human papillomavirus (HPV), while its effect on cervical intraepithelial neoplasia (CIN) caused by high risk type of HPVs has not been reported. PATIENT CONCERNS: Three patients with low grade CIN and positive high risk HPV types (HPV 16, 31, 52, 56, 58) are reported in this study. DIAGNOSIS: The diagnosis was based on identification of HPV types and abnormal cytological findings. INTERVENTIONS: The 3 patients were treated with local hyperthermia from ceramic heating (surface temperature, 44°C) to cervix. The treatment was delivered once a day for 3 consecutive days, plus two similar treatments 10 ± 3 days later, with each session lasting 30 minutes. HPV and cytology test were performed 3 months thereafter. OUTCOMES: All the 3 patients recovered to normal cytological findings. Two of the patients were negative for HPV, the remaining patient with pre-treatment HPV 56 and 58 positivity changed to HPV58 positive alone. CONCLUSION: This pilot observation inspires that mild local hyperthermia be recommended as a new method in the treatment of CIN patients with persistent HPV infection, once validated by qualified RCT.


Assuntos
Neoplasia Intraepitelial Cervical/terapia , Hipertermia Induzida/métodos , Neoplasias do Colo do Útero/terapia , Adulto , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/virologia
6.
J Laryngol Otol ; 134(6): 533-540, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32616096

RESUMO

OBJECTIVE: To evaluate the effect of definitive radiotherapy dose on survival in patients with human papillomavirus positive oropharyngeal carcinoma. METHODS: Human papillomavirus positive oropharyngeal carcinoma patients staged T1-3 and N0-2c, who received definitive radiotherapy (fraction sizes of 180 cGy to less than 220 cGy), were identified from the National Cancer Database 2010-2014 and stratified by radiation dose (50 Gy to less than 66 Gy, or 66 Gy or more). RESULTS: A total of 2173 patients were included, of whom 124 (6 per cent) received a radiation dose of 50 Gy to less than 66 Gy. With a median follow up of 33.8 months, patients had a 3-year overall survival rate of 88.6 per cent (95 per cent confidence interval = 87.1-90.1 per cent). On multivariate Cox analysis, a radiotherapy dose of 50 Gy to less than 66 Gy (hazard ratio = 0.95, 95 per cent confidence interval = 0.52-1.74, p = 0.86) was not a predictor of increased mortality risk. CONCLUSION: Human papillomavirus positive oropharyngeal carcinoma patients had excellent outcomes with definitive radiotherapy doses of 50 Gy to less than 66 Gy. These results further support patients enrolling into clinical trials for radiation dose de-escalation.


Assuntos
Carcinoma/radioterapia , Neoplasias Orofaríngeas/mortalidade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/virologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Radioterapia/métodos , Taxa de Sobrevida
7.
Cancer Invest ; 38(7): 394-405, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32643440

RESUMO

The study investigated the human cytomegalovirus (HCMV) and human papillomavirus (HPV) in gliomas. A retrospective study was conducted on 112 samples. HCMV was investigated by PCR, in situ hybridization (ISH) and immunohistochemistry. HPV was tested by PCR and DNA ISH. HCMV was identified in 60 gliomas, including 55 GBM. However, RNA ISH and immunohistochemistry failed to detect HCMV positivity. HPV was identified in 44 GBM. No significant relationship was identified between HCMV and HPV and tumour characteristics (p > 0.05). Our findings support the HCMV and HPV presence in gliomas. Further assays are required to more explore the potential efficient antiviral management.


Assuntos
Neoplasias Encefálicas/virologia , Citomegalovirus/isolamento & purificação , Glioma/virologia , Papillomaviridae/isolamento & purificação , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Citomegalovirus/genética , Infecções por Citomegalovirus/virologia , Feminino , Glioma/mortalidade , Glioma/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Tunísia , Adulto Jovem
8.
PLoS One ; 15(7): e0235264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32658921

RESUMO

OBJECTIVE: To identify health systems-level barriers to treatment for women who screened positive for high-risk human papillomavirus (hrHPV) in a cervical cancer prevention program in Kenya. METHODS: In a trial of implementation strategies for hrHPV-based cervical cancer screening in western Kenya in 2018-2019, women underwent hrHPV testing offered through community health campaigns, and women who tested positive were referred to government health facilities for cryotherapy. The current analysis draws on treatment data from this trial, as well as two observational studies that were conducted: 1) periodic assessments of the treatment sites to ascertain availability of resources for treatment and 2) surveys with treatment providers to elicit their views on barriers to care. Bivariate analyses were performed for the site assessment data, and the provider survey data were analyzed descriptively. RESULTS: Seventeen site assessments were performed across three treatment sites. All three sites reported instances of supply stockouts, two sites reported treatment delays due to lack of supplies, and two sites reported treatment delays due to provider factors. Of the 16 providers surveyed, ten (67%) perceived lack of knowledge of HPV and cervical cancer as the main barrier in women's decision to get treated, and seven (47%) perceived financial barriers for transportation and childcare as the main barrier to accessing treatment. Eight (50%) endorsed that providing treatment free of cost was the greatest facilitator of treatment. CONCLUSION: Patient education and financial support to reach treatment are potential areas for intervention to increase rates of hrHPV+ women presenting for treatment. It is also essential to eliminate barriers that prevent treatment of women who present, including ensuring adequate supplies and staff for treatment.


Assuntos
Crioterapia/estatística & dados numéricos , Detecção Precoce de Câncer/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Infecções por Papillomavirus/terapia , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Serviços de Saúde Comunitária/economia , Serviços de Saúde Comunitária/organização & administração , Serviços de Saúde Comunitária/estatística & dados numéricos , Crioterapia/economia , Detecção Precoce de Câncer/economia , Feminino , Alocação de Recursos para a Atenção à Saúde/economia , Alocação de Recursos para a Atenção à Saúde/organização & administração , Alocação de Recursos para a Atenção à Saúde/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Implementação de Plano de Saúde/economia , Implementação de Plano de Saúde/organização & administração , Implementação de Plano de Saúde/estatística & dados numéricos , Promoção da Saúde/economia , Promoção da Saúde/organização & administração , Promoção da Saúde/estatística & dados numéricos , Acesso aos Serviços de Saúde/economia , Acesso aos Serviços de Saúde/organização & administração , Acesso aos Serviços de Saúde/estatística & dados numéricos , Mão de Obra em Saúde/organização & administração , Mão de Obra em Saúde/estatística & dados numéricos , Humanos , Quênia/epidemiologia , Programas de Rastreamento/economia , Programas de Rastreamento/organização & administração , Estudos Observacionais como Assunto , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Educação de Pacientes como Assunto , Encaminhamento e Consulta/estatística & dados numéricos , População Rural/estatística & dados numéricos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
9.
BMC Bioinformatics ; 21(1): 233, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513098

RESUMO

BACKGROUND: The detection of known human papillomaviruses (PVs) from targeted wet-lab approaches has traditionally used PCR-based methods coupled with Sanger sequencing. With the introduction of next-generation sequencing (NGS), these approaches can be revisited to integrate the sequencing power of NGS. Although computational tools have been developed for metagenomic approaches to search for known or novel viruses in NGS data, no appropriate tool is available for the classification and identification of novel viral sequences from data produced by amplicon-based methods. RESULTS: We have developed PVAmpliconFinder, a data analysis workflow designed to rapidly identify and classify known and potentially new Papillomaviridae sequences from NGS amplicon sequencing with degenerate PV primers. Here, we describe the features of PVAmpliconFinder and its implementation using biological data obtained from amplicon sequencing of human skin swab specimens and oral rinses from healthy individuals. CONCLUSIONS: PVAmpliconFinder identified putative new HPV sequences, including one that was validated by wet-lab experiments. PVAmpliconFinder can be easily modified and applied to other viral families. PVAmpliconFinder addresses a gap by providing a solution for the analysis of NGS amplicon sequencing, increasingly used in clinical research. The PVAmpliconFinder workflow, along with its source code, is freely available on the GitHub platform: https://github.com/IARCbioinfo/PVAmpliconFinder.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Papillomaviridae/isolamento & purificação , Interface Usuário-Computador , DNA Viral/química , DNA Viral/metabolismo , Humanos , Papillomaviridae/genética , Fluxo de Trabalho
10.
PLoS One ; 15(6): e0233974, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542012

RESUMO

BACKGROUND: The surrogate immunohistochemical marker, p16INK4a, is used in clinical practice to determine the high-risk human papillomavirus (HPV) status of oropharyngeal squamous cell carcinomas (OPSCC). With a specificity of 83%, this will misclassify some patients compared with direct HPV testing. Patients who are p16INK4a-positive but HPV DNA-negative, or RNA-negative, may be unsuitable for treatment de-escalation aimed at reducing treatment-related side effects. We aimed to identify cost-effective serum markers to improve decision making for patients at risk of misclassification by p16INK4a alone. METHODS: Serum proteins from pre-treatment samples of 36 patients with OPSCC were identified and quantified using label-free mass spectrometry-based proteomics. HPV-status was determined using p16INK4a/HPV DNA and E6/E7 mRNA. Serum protein expressions were compared between groups of patients according to HPV status, using the unpaired t-test with a Benjamini-Hochberg correction. ROC curves (AUC) were calculated with SPSS (v25). RESULTS: Of 174 serum proteins identified, complement component C7 (C7), apolipoprotein F (ApoF) and galectin-3-Binding Protein (LGALS3BP) significantly differed between HPV-positive and -negative tumors (AUC ranging from 0.84-0.87). ApoF levels were more than twice as high in the E6/E7 mRNA HPV-positive group than HPV-negative. CONCLUSIONS: Serum C7, ApoF and LGALS3BP levels discriminate between HPV-positive and HPV-negative OPSCC. Further studies are needed to validate these host immunity-related proteins as markers for HPV-associated OPSCC.


Assuntos
Antígenos de Neoplasias/sangue , Apolipoproteínas/sangue , Biomarcadores Tumorais/sangue , Complemento C7/análise , Neoplasias Orofaríngeas/sangue , Neoplasias Orofaríngeas/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Inibidor p16 de Quinase Dependente de Ciclina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue
11.
APMIS ; 128(8): 497-505, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32562292

RESUMO

Primary high-risk human papillomavirus (hrHPV) DNA testing has been introduced in several countries worldwide, including The Netherlands. The objective of this study was to compare three automated workflow procedures for hrHPV testing of which the hrHPV detection assays meet the international guidelines for HPV testing. To mimic a realistic screening situation, we aimed to process 15 000 residual PreservCyt cervical samples in a period of 3 months. During a 3 months period, four technicians were involved in processing 5000 specimens per month on three automated platforms, (1) Qiagen Digene® HC2 HPV DNA test (HC2, signal amplification); (2) Roche Cobas® HPV test (DNA amplification), and (3) Hologic Aptima® HPV test (RNA amplification). We measured and scored general aspects (time-to-results, hands-on-time (HOT)), maintenance, pre-run, run and post-run aspects, inventory (orders, storage), and number of errors on a scale from 1 to 10. As determined for one complete workflow each, maximum processing capacity and HOT were 296 samples and 2 h:55 m, 282 samples and 3 h:20 m, and 264 samples and 4 h:15 m for Aptima, Cobas, and HC2, respectively. The mean throughput time per run was 5 h:51 m for Cobas in which 94 samples could be processed. For Aptima, the mean throughput time per run was 6 h:30 m for 60 samples. Mean throughput time for HC2 is longer since results were provided on day 2. In this study, the fully automated Aptima workflow scores best with a 7.2, followed by Cobas with a score of 7.1 and HC2 with a score of 5.8. Although all HPV tests used in this comparison meet the international test guidelines, the performance (workflow) characteristics of the assays vary widely. A specific choice of a laboratory for high-throughput testing can be different based on the laboratory's demands, but also hands-on-time, time-to-results/ # samples, maintenance, pre-run, run and post-run parameters, consumables, technical support, and number of errors are important operational factors for the selection of a fully automated workflow for hrHPV testing.


Assuntos
Automação Laboratorial/métodos , Ensaios de Triagem em Larga Escala , Testes de DNA para Papilomavírus Humano/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Fluxo de Trabalho , Feminino , Humanos , Países Baixos , Papillomaviridae/classificação , Papillomaviridae/genética , Estudos Retrospectivos , Fatores de Tempo
12.
Acta Cytol ; 64(5): 442-451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32599588

RESUMO

INTRODUCTION: Persistent infection with high-risk human papillomavirus (HPV) types is associated with high-grade intraepithelial lesions (HSILs) and invasive cervical cancer. The host immune response plays a key role in whether HPV clears or persists. Most studies on local immune response to HPV collect cervical mucus in order to quantify secreted cytokines; however, cells located inside the tissue can release different cytokines associated with HPV infection. OBJECTIVE: This study compared the cytokine levels in cervical biopsy specimens of women with abnormal colposcopic findings according to the histopathological results: low-grade intraepithelial lesion (LSIL), HSIL, and no intraepithelial lesion (NSIL). METHODS: A cross-sectional study enrolling 141 cervical biopsy specimens examined the cytokine profile for interleukin (IL-) 2, IL-4, IL-10, IL-12, IL-17, and IL-23 and interferon-γ, using the Luminex assay/ELISA. Differences in cytokine levels among the cervical lesion groups were assessed using the Kruskal-Wallis test. RESULTS: The 141 specimens included 90 HSILs, 22 LSILs, and 29 NSILs. IL-2 levels were significantly higher in NSIL samples than in LSIL or in HSIL samples (p = 0.0001) and IL-23 levels were significantly higher in NSIL than in HSIL samples (p = 0.003). CONCLUSIONS: Our study shows that in samples from the lesion site point, 2 important pro-inflammatory cytokines, IL-2 and IL-23, are downregulated in HPV lesions.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasia Intraepitelial Cervical/patologia , Interleucina-23/metabolismo , Interleucina-2/metabolismo , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/patologia , Adulto , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/virologia , Estudos Transversais , Regulação para Baixo , Feminino , Humanos , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia
13.
J Cancer Res Ther ; 16(1): 170-172, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362631

RESUMO

With the discovery of v-Raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors, new treatment possibilities arose against metastatic melanoma. A frequent adverse effect of BRAF inhibitor therapy is the induction of epithelial proliferations such as cutaneous squamous cell carcinoma and verrucous papilloma. Here, we describe a case in which a patient developed extensive anal epithelial proliferations resembling condylomata acuminata, after starting vemurafenib treatment. This adverse effect has rarely been reported in the literature. Interestingly, the lesions in our patient were negative for human papillomavirus, and mutations in BRAF, Neuroblastoma rat sarcoma viral oncogene homolog (NRAS), Kirsten rat sarcoma viral oncogene homolog (KRAS), and Harvey rat sarcoma viral oncogene homolog (HRAS) were not detected. Different pathways can contribute to these epithelial proliferations resembling condylomata acuminata. We show the relevance of a detailed history at the beginning and during treatment, instructions, education, and dermatological follow-up (including the genital area) for patients treated with BRAF inhibitors. Condylomata acuminata can influence the quality of life and are treated, in an early stage, with cryotherapy, coagulation, imiquimod, and/or CO2 laser therapy.


Assuntos
Neoplasias do Ânus/diagnóstico , Proliferação de Células , Condiloma Acuminado/diagnóstico , Melanoma/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Vemurafenib/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias do Ânus/induzido quimicamente , Neoplasias do Ânus/genética , Condiloma Acuminado/induzido quimicamente , Diagnóstico Diferencial , GTP Fosfo-Hidrolases/genética , Humanos , Masculino , Melanoma/genética , Melanoma/patologia , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Neoplasias Epiteliais e Glandulares/induzido quimicamente , Neoplasias Epiteliais e Glandulares/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
14.
PLoS One ; 15(5): e0232871, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407339

RESUMO

Human papillomavirus (HPV) is responsible for the rise in the incidence of cancer in the oropharynx, tonsils, and base of the tongue (i.e., HPV-related subsites). HPV triggered the changes in the epidemiology of oropharyngeal and oral cavity cancer (OPC/OCC) in Asia, Europe, North America, and Oceania. Hence, the incidence of cancer in HPV-related subsites is augmenting, while that in other HPV-unrelated subsites is decreasing. In South America, although the incidence of HPV-positive tumors has gradually increased, there is an atypically low prevalence of HPV in people with OPC/OCC. To clarify whether this dramatic shift in incidence trends also occurred in this population, we estimated the burden of HPV on the incidence trends of OPCs/OCCs in São Paulo city in Brazil. In this population-based study, we categorized OPCs/OCCs by HPV-related and HPV-unrelated subsites. We used Poisson regression to assess the age-standardized incidence rates (ASRs) stratified by sex and age groups, as well as to examine the age-period-cohort effects. There were 15,391 cases of OPCs/OCCs diagnosed in HPV-related (n = 5,898; 38.3%) and HPV-unrelated (n = 9,493; 61.7%) subsites. Overall, the ASRs decreased for most subsites, for both sexes and for all age groups, except for HPV-related OPC/OCC in young males and females, which increased by 3.8% and 8.6% per year, respectively. In the birth-cohort-effect analysis, we identified an increasing risk for HPV-related OPC/OCC in both sexes in recent birth cohorts; however, this risk was sharply decreased in HPV-unrelated subsites. Our data demonstrate an emerging risk for HPV-related OPC/OCC in young people, which supports prophylactic HPV vaccination in this group.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Neoplasias Bucais/epidemiologia , Neoplasias Orofaríngeas/epidemiologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Brasil/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Fatores Sexuais , Adulto Jovem
15.
BMC Infect Dis ; 20(1): 375, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460721

RESUMO

BACKGROUND: Sexually transmitted infections (STIs) cause a major public health problem that affect both men and women in developing and developed countries. The aim of the study was to estimate the prevalence of 11 STIs among women who voluntarily participated in the study, while seeking gynecological checkup. The existence of an association between the presence of pathogens and symptoms and various sociodemographic risk factors was assessed. METHODS: A total of 505 vaginal and cervical specimens were collected from women above 18 years of age, with or without symptoms related to gynecological infections. Nucleic acid was extracted and samples were tested by real-time PCR for the following pathogens: Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum, Urealplasma parvum, Trichomonas vaginalis, Mycoplasma hominis, Mycoplasma girerdii, Gardnerella vaginalis, Candida albicans and Human Papillomavirus (HPV). Positive HPV samples underwent genotyping using a microarray system. RESULTS: Of the 505 samples, 312 (62%) were screened positive for at least one pathogen. Of these, 36% were positive for Gardnerella vaginalis, 35% for Ureaplasma parvum, 8% for Candida albicans, 6.7% for HPV, 4.6% for Ureaplasma urealyticum, 3.6% for Mycoplasma hominis, 2% for Trichomonas vaginalis, 0.8% for Chlamydia trachomatis, 0.4% for Mycoplasma girerdii, 0.2% for Mycoplasma genitalium and 0.2% for Neisseria gonorrhoeae. Lack of symptoms was reported in 187 women (37%), among whom 61% were infected. Thirty-four samples were HPV positive, with 17 high risk HPV genotypes (HR-HPV); the highest rates being recorded for types 16 (38%), 18 (21%) and 51 (18%). Out of the 34 HPV positives, 29 participants had HR-HPV. Association with various risk factors were reported. CONCLUSIONS: This is the first study that presents data about the presence of STIs among women in Lebanon and the MENA region by simultaneous detection of 11 pathogens. In the absence of systematic STI surveillance in Lebanon, concurrent screening for HPV and PAP smear is warranted.


Assuntos
Doenças Sexualmente Transmissíveis/epidemiologia , Adulto , Colo do Útero/microbiologia , Colo do Útero/parasitologia , Colo do Útero/virologia , Chlamydia trachomatis/genética , Chlamydia trachomatis/isolamento & purificação , Estudos Transversais , Feminino , Gardnerella vaginalis/genética , Gardnerella vaginalis/isolamento & purificação , Humanos , Líbano/epidemiologia , Masculino , Epidemiologia Molecular , Infecções por Mycoplasma/epidemiologia , Mycoplasma genitalium/genética , Mycoplasma genitalium/isolamento & purificação , Mycoplasma hominis/genética , Mycoplasma hominis/isolamento & purificação , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/isolamento & purificação , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Fatores de Risco , Doenças Sexualmente Transmissíveis/microbiologia , Doenças Sexualmente Transmissíveis/parasitologia , Doenças Sexualmente Transmissíveis/virologia , Trichomonas vaginalis/genética , Trichomonas vaginalis/isolamento & purificação , Ureaplasma/genética , Ureaplasma/isolamento & purificação , Vagina/microbiologia , Vagina/parasitologia , Vagina/virologia , Esfregaço Vaginal , Adulto Jovem
16.
Acta Cytol ; 64(5): 433-441, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32396902

RESUMO

OBJECTIVE: The objective of this study was to calculate the positive rate and overall concordance rate of high-risk human papillomavirus (hrHPV) test and cytology using self-sampled and physician-sampled cervicovaginal tests and to compare both specimens. METHODS: In collaboration with 3 private hospitals in Sapporo city, 300 women visiting these organizations were enrolled in the study by previously signing an informed consent. From these women, both types of samples (self-obtained and physician-sampled) were obtained at the same time. HrHPV test and cytology were performed on both specimens, and the positive rate and overall concordance rate were calculated to compare both specimens. RESULTS: HrHPV-positive women were 13.7% in physician-sampled specimens and 14.7% in self-sampled specimens, with an overall concordance rate of 96.3% (95% confidence interval [CI]: 94-98%). On the other hand, the positive rate of the cases higher than or equal to atypical squamous cells of undetermined significance (ASCUS) on cytology was different between both groups, that is, 12.3% in physician-obtained and 5.3% in self-sampled specimens; the overall concordance rate was 90.7% (95% CI: 87-94%), indicating an apparent decrease in the positive rate of cytology in self-obtained specimens. CONCLUSION: HrHPV test and cytology were performed on parallel samples obtained by the patients with a self-sampling tool and by the physician. The positive rate of cytology was considerably different between these specimens, while almost equivalent results were obtained for hrHPV test in both specimens. It was concluded that hrHPV test may be safely and accurately performed on self-obtained cervicovaginal samples by the help of a self-sampling device in the Japanese population as a first screening tool, with equivalent results to physician-obtained specimens.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Citodiagnóstico/métodos , Detecção Precoce de Câncer/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Manejo de Espécimes/métodos , Neoplasias do Colo do Útero/epidemiologia , Adulto , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Manejo de Espécimes/normas , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/normas , Esfregaço Vaginal/estatística & dados numéricos , Adulto Jovem
17.
Hum Genet ; 139(6-7): 919-939, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32435828

RESUMO

Human papillomaviruses (HPVs) infect mucosal or cutaneous stratified epithelia. There are 5 genera and more than 200 types of HPV, each with a specific tropism and virulence. HPV infections are typically asymptomatic or result in benign tumors, which may be disseminated or persistent in rare cases, but a few oncogenic HPVs can cause cancers. This review deals with the human genetic and immunological basis of interindividual clinical variability in the course of HPV infections of the skin and mucosae. Typical epidermodysplasia verruciformis (EV) is characterized by ß-HPV-driven flat wart-like and pityriasis-like cutaneous lesions and non-melanoma skin cancers in patients with inborn errors of EVER1-EVER2-CIB1-dependent skin-intrinsic immunity. Atypical EV is associated with other infectious diseases in patients with inborn errors of T cells. Severe cutaneous or anogenital warts, including anogenital cancers, are also driven by certain α-, γ-, µ or ν-HPVs in patients with inborn errors of T lymphocytes and antigen-presenting cells. The genetic basis of HPV diseases at other mucosal sites, such as oral multifocal epithelial hyperplasia or juvenile recurrent respiratory papillomatosis (JRRP), remains poorly understood. The human genetic dissection of HPV-driven lesions will clarify the molecular and cellular basis of protective immunity to HPVs, and should lead to novel diagnostic, preventive, and curative approaches in patients.


Assuntos
Predisposição Genética para Doença , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Dermatopatias Infecciosas/patologia , Infecções Tumorais por Vírus/patologia , Humanos , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Dermatopatias Infecciosas/genética , Dermatopatias Infecciosas/virologia , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/virologia
18.
Adv Cancer Res ; 146: 115-137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32241386

RESUMO

Human papillomavirus (HPV) infection is the primary risk factor for cervical cancer. While the HPV vaccine significantly reduces the risk of HPV infection and subsequent cervical cancer diagnosis, underuse is linked to lack of knowledge of its effectiveness in preventing cervical cancer. The purpose of this study was to evaluate a cancer educational intervention (titled "MOVENUP") to improve knowledge of cervical cancer, HPV, and the HPV vaccine among predominantly African American communities in South Carolina. The MOVENUP cancer educational intervention was conducted among participants residing in nine South Carolina counties who were recruited by community partners. The 4.5-h MOVENUP cancer educational intervention included a 30-min module on cervical cancer, HPV, and HPV vaccination. A six-item investigator-developed instrument was used to evaluate pre- and post-intervention changes in knowledge related to these content areas. Ninety-three percent of the 276 participants were African American. Most participants reporting age and gender were 50+ years (73%) and female (91%). Nearly half of participants (46%) reported an annual household income <$40,000 and 49% had not graduated from college. Statistically significant changes were observed at post-test for four of six items on the knowledge scale (P<0.05), as compared to pre-test scores. For the two items on the scale in which statistically significant changes were not observed, this was due primarily due to a baseline ceiling effect.


Assuntos
Intervenção Educacional Precoce/métodos , Grupos Étnicos/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/prevenção & controle , Vacinação/psicologia , Feminino , Educação em Saúde , Humanos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia
19.
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
20.
Acta Cytol ; 64(5): 420-424, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32235115

RESUMO

BACKGROUND: Nearly 500,000 new cases of cervical cancer are estimated annually worldwide. Three vaccines are currently licensed to prevent cervical cancer. The success of vaccination depends mainly on the prevalence of HPV genotypes, and many cases of HPV infection have been diagnosed after vaccination. Our aim was to search for HPV genotyping in cervical samples to verify the proportion of women that remain susceptible to infection even after vaccination. METHODS: 21,017 liquid-based cervical (LBC) specimens were received for cytology and HPV detection from 2015 to 2018. Before slide preparations for cytology, a 1,000-µL aliquot was taken from the LBC fixative and subjected to automated DNA extraction and multiplex PCR followed by capillary electrophoresis to detect and classify HPV. RESULTS: HPV was detected in 895 (4.3%) specimens. The most prevalent genotype was HPV-16, followed by HPV-58 and HPV-66. A total of 258 (28.8%) cases were positive for high-risk (HR)-HPV types (66, 59, 39, 56, 30, 35, 53, 51, 68, 82, and 70) that are not covered by the HPV vaccines. CONCLUSION: A significant proportion of HPV types detected in cytological specimens are representative of HR-HPV not covered by the available vaccines. The health system should be aware of the considerable percentage of women who are not being immunized and will continue to need cervical cancer screening.


Assuntos
Citodiagnóstico/métodos , Detecção Precoce de Câncer/métodos , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Brasil/epidemiologia , DNA Viral/análise , DNA Viral/genética , Feminino , Genótipo , Humanos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Prevalência , Lesões Intraepiteliais Escamosas Cervicais/prevenção & controle , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação
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