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1.
Anticancer Res ; 40(4): 2117-2123, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234904

RESUMO

BACKGROUND/AIM: The incidence of human papilloma virus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has been increasing in the last decades. Analysis of oral brushing or rinsing samples for screening or stratification could potentially improve screening and prevention. PATIENTS AND METHODS: Oral brushes and mouthwashes were taken from 20 patients with HPV-associated HNSCC before definite therapy. HPV genotyping was performed for the detection of 14 high-risk HPV subtypes and correlated to DNA isolated from tumor tissue. RESULTS: Ten of 20 patients were tested HPV positive by using either method. There was a significant correlation between macroscopic visibility of tumor and positive HPV detection (p<0.001) and HPV detection and tumor size (p<0.001). HPV was detected in all macroscopically visible tumors. Half of the HPV cases who had macroscopically invisible tumors were missed by both methods. CONCLUSION: Both techniques are limited in the detection of macroscopically non-visible and small tumors. Therefore, the application of these techniques for screening or diagnosis of HNSCC is not recommended.


Assuntos
Neoplasias Orofaríngeas/genética , Papillomaviridae/genética , Infecções por Papillomavirus/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Idoso , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Genótipo , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 16/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Antissépticos Bucais/análise , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae/isolamento & purificação , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
2.
Cancer Invest ; 38(4): 228-239, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32208057

RESUMO

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


Assuntos
Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/citologia , Células-Tronco Neoplásicas/patologia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , ADP-Ribosil Ciclase 1/análise , ADP-Ribosil Ciclase 1/imunologia , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Biópsia , Neoplasia Intraepitelial Cervical/imunologia , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/imunologia , Colo do Útero/patologia , Colo do Útero/virologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe I/análise , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe II/análise , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Integrina beta1/análise , Integrina beta1/imunologia , Integrina beta1/metabolismo , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , Gradação de Tumores , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/virologia , Papillomaviridae/imunologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia
3.
Anticancer Res ; 40(3): 1513-1517, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132051

RESUMO

BACKGROUND/AIM: Cervical cancer is the most common cancer among women in Ethiopia. The objective was to evaluate the participation rate of a free of charge vaginal self-sample (Aptima multitest swab, Hologic) for the detection of human papillomavirus (HPV) in an Ethiopian cohort. PATIENTS AND METHODS: Specimens were collected from women employed by Ethiopian Airlines in Addis Abeba (N=5950). Samples were analysed for the presence of high-risk (HR) HPV mRNA by the Aptima HPV assay (Hologic) and HPV positive women were referred for cytology. Identification of HPV types among HPV positive samples was performed by Modified general primer-PCR and Luminex assay. RESULTS: Participation rate was 3.1% and the prevalence of HPV mRNA was 20.6% (37/180). CONCLUSION: Primary HPV mRNA screening with vaginal self-sampling may be an acceptable approach in Ethiopia. One out of five women harbor HPV in their vaginal self-sample in agreement with other similar studies from the region.


Assuntos
Papillomaviridae/genética , RNA Mensageiro/análise , RNA Viral/análise , Vagina/virologia , Adolescente , Adulto , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Etiópia/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prevalência , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Vagina/patologia , Esfregaço Vaginal , Adulto Jovem
4.
BMC Infect Dis ; 20(1): 144, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059635

RESUMO

BACKGROUND: The southeastern US is an epicenter for incident HIV in the US with high prevalence of human papillomavirus (HPV) co-infections. However, epidemiologies of HPV-associated clinical conditions (CC) among people living with HIV-1 infection (PLWH) are not fully known. METHODS: Electronic medical records (EMR) of PLWH attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analyzed. The retrospective study was nested within the University of Alabama at Birmingham HIV clinical cohort, which has electronically collected over 7000 PLWH's clinical and sociobehavioral data since 1999. Incidence rates of HPV-related CC including anogenital warts, penile, anal, cervical, and vaginal/vulvar low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) were estimated per 10,000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of incident CC. All rates and trends were stratified by gender and race. RESULTS: Of the 4484 PLWH included in the study (3429 men, 1031 women, and 24 transgender), we observed 1038 patients with HPV-related CC. The median nadir CD4 count (cells/uL) was higher in the HPV-condition free group than the case groups (P < 0.0001). Anogenital warts, anal LSIL, HSIL, and cancer were more likely to be diagnosed among HIV-infected men than women. White men presented more frequently with anal LSIL and anal and penile cancers than black men (P < 0.03). White women were also more likely to be diagnosed with cervical HSIL (P = 0.023) and cancer (P = 0.037) than black women. CONCLUSIONS: There were significant differences between gender and race with incidence of HPV-related CC among HIV patients. EMR-based studies provide insights on understudied HPV-related anogenital conditions in PLWH; however, large-scale studies in other regions are needed to generalize current findings and draw public health attention to co-infection induced non-AIDS defining comorbidities among PLWH.


Assuntos
Infecções por HIV/epidemiologia , Infecções por Papillomavirus/epidemiologia , Adulto , Afro-Americanos/estatística & dados numéricos , Canal Anal/virologia , Contagem de Linfócito CD4 , Estudos de Coortes , Comorbidade , Condiloma Acuminado/epidemiologia , Condiloma Acuminado/virologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Infecções por HIV/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Prevalência , Estudos Retrospectivos , Sudeste dos Estados Unidos/epidemiologia
5.
Cancer Sci ; 111(4): 1407-1416, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32012407

RESUMO

Irradiation, or chemoradiotherapy, is a curative treatment for oropharyngeal squamous cell carcinoma (OPSCC). Its invasiveness, however, can often negate its efficacy. Therefore, developing methods to predict which patients would benefit from irradiation is urgent. Promoter DNA hypermethylation was recently reported to correlate with favorable OPSCC prognosis. It is still unclear, however, whether there is an association between promoter DNA methylation and response to irradiation. In this study, we analyzed DNA methylation in the specimens from 40 OPSCC patients who had undergone irradiation, using the Infinium assay. Our results showed significant correlation between high levels of promoter DNA methylation and better response to treatment (P < 0.01). We used the 10 most differentially-methylated genes between responders and non-responders to develop a panel of predictive markers for efficacy. Our panel had high sensitivity, specificity and accuracy (92%, 93% and 93%, respectively). We conducted pyrosequencing to quantitatively validate the methylation levels of 8 of the 10 marker genes (ROBO1, ULK4P3, MYOD1, LBX1, CACNA1A, IRX4, DPYSL3 and ELAVL2) obtained by Infinium. The validation by pyrosequencing showed that these 8 genes had a high prediction performance for the training set of 40 specimens and for a validation set of 35 OPSCC specimens, showing 96% sensitivity, 89% specificity and 94% accuracy. Methylation of these markers correlated significantly with better progression-free and overall survival rates, regardless of human papillomavirus status. These results indicate that increased DNA methylation is associated with better responses to irradiation therapy and that DNA methylation can help establish efficacy prediction markers in OPSCC.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA/efeitos da radiação , Neoplasias Orofaríngeas/radioterapia , Infecções por Papillomavirus/radioterapia , Idoso , Metilação de DNA/genética , Epigenômica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae/patogenicidade , Papillomaviridae/efeitos da radiação , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Regiões Promotoras Genéticas/efeitos da radiação
6.
DNA Cell Biol ; 39(4): 645-653, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32045269

RESUMO

Cervical cancer (CC) is a malignant tumor that could seriously endanger women's life and health, of which cervical squamous cell carcinoma (CESC) accounts for more than 80%. High-risk human papillomavirus (HR-HPV) infection is the primary cause of CC. The 5-year survival rate is low due to poor prognosis. We need to explore the pathogenesis of CC and seek effective biomarkers to improve prognosis. The purpose of this research is to construct an HR-HPV-related long non-coding RNA (lncRNA) signature for predicting the survival and finding the biomarkers related to CC prognosis. First, we downloaded the CESC data from The Cancer Genome Atlas (TCGA) database to find HR-HPV-related lncRNAs in CC. Then, the differentially expressed lncRNAs were analyzed by univariate and multivariate Cox regression. Six lncRNAs were found to be associated with the prognosis and can be used as independent prognostic factors. Next, based on these prognostic genes, we established a risk score model, which showed that patients with higher score had poorer prognosis and higher mortality. Moreover, the Kaplan-Meier curve of the model indicated that the model was statistically significant (p < 0.05). The survival-receiver operating characteristic curve showed that the model could also predict the survival of CC patients (the area under the curve, AUC = 0.65). More importantly, nomogram was drawn with clinical features and risk score, which verified the above conclusion, and its calibration curve and c-index index fully demonstrated that the prediction model could predict the progress of CC. We also validated the risk score model in head and neck cancer, and the results indicated that the model had obvious prognostic ability. Finally, we analyzed the correlation between clinical features and survival, and found that neoplasm cancer (p < 0.000) and risk score (p < 0.000) were independent prognostic factors for CC. In conclusion, the study established HR-HPV-related lncRNA signature, which provided a reliable prognostic tool, and was of great significance for finding the biomarkers related to HR-HPV infection in CC.


Assuntos
Biomarcadores Tumorais/genética , Papillomaviridae/genética , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Adulto , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prognóstico , Taxa de Sobrevida
7.
Crit Rev Oncol Hematol ; 147: 102866, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32058913

RESUMO

The precursor lesion of vulvar squamous cell carcinoma (VSCC), namely vulvar intraepithelial neoplasia (VIN), is classified as: human papillomavirus (HPV)-related high grade squamous intraepithelial lesion (HSIL), and HPV-independent differentiated VIN (dVIN). Traditionally, histology and immunohistochemistry (IHC) have been the basis of diagnosis and classification of VIN. HSIL shows conspicuous histological atypia, and positivity on p16-IHC, whereas dVIN shows less obvious histological atypia, and overexpression or null-pattern on p53-IHC. For both types of VIN, other diagnostic immunohistochemical markers have also been evaluated. Molecular characterization of VIN has been attempted in few recent studies, and novel genotypic subtypes of HPV-independent VSCC and VIN have been identified. This systematic review appraises the VSCC precursors identified so far, focusing on histology and biomarkers (immunohistochemical and molecular). To gain further insights into the carcinogenesis and to identify additional potential biomarkers, gene expression omnibus (GEO) datasets on VSCC were analyzed; the results are presented.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Neoplasia Intraepitelial Cervical/patologia , Papillomaviridae/isolamento & purificação , Neoplasias Vulvares/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Neoplasias Vulvares/virologia
8.
Life Sci ; 245: 117383, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32007572

RESUMO

AIMS: The current article provides a detailed account of the current understanding of molecular and clinico-pathological aspects of Human papilloma virus (HPV) driven head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: The literature review included most of the landmark trials and clinical studies related to the HPV driven HNSCC. KEY FINDINGS: HPV positive HNSCC differ distinctly from HPV negative tobacco-related HNSCC, especially in oropharyngeal region. Therefore, the American joint committee on cancer`s latest manual for classification and staging of cancer suggests a separate staging system for HPV positive oropharyngeal cancers. Despite the younger patients being affected and the high propensity for cervical metastasis, the HPV positive oropharyngeal cancers respond much better to the treatment. The association with wild type TP53 and low EGFR expression confers the favorable prognosis in HPV driven HNSCC. Since the association is not universal, we suggest checking for p53 and EGFR expression status before considering de-intensification of therapy. In addition, the presence of matted lymph nodes and five or more nodes could mean relatively poorer prognosis, and are not suitable for de-intensification of therapy. The same is also true probably with higher T stage and co-existing tobacco use. The methods for the detection of p16, HPV DNA, HPV E6/E7 mRNA, anti-E6/E7 antibodies, in tissue, in serum and in saliva of patients, along with their clinical implications are also discussed. SIGNIFICANCE: This article provides latest developments on the HPV driven HNSCC. 'Diagnosis of transcriptionally active HPV infection,' 'Modalities for surveillance,' 'Implication of de-escalation of therapy' are some of the critical issues that could serve the medical, the research as well as the patient communities.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias de Cabeça e Pescoço/virologia , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas/etiologia , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Infecções por Papillomavirus/patologia
9.
An Bras Dermatol ; 95(1): 78-81, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31889590

RESUMO

The number of individuals with tattoos has been increasing worldwide, alongside with reports of complications varying from reactions to the injected pigments to infections caused by agents inoculated in the pigmentation process. The diagnosis of such unwanted events can be obtained through complementary non-invasive methods, preserving the maximum of the tattoo design. The authors present two cases of patients with warts on tattooing, and correlate their clinical aspects to in vivo and ex vivo dermoscopy, and to the findings in the histopathological examination, aiming to determine patterns that aid the diagnosis of these lesions without performing biopsy.


Assuntos
Infecções por Papillomavirus/diagnóstico por imagem , Infecções por Papillomavirus/patologia , Tatuagem/efeitos adversos , Verrugas/diagnóstico por imagem , Verrugas/patologia , Adulto , Biópsia , Corantes/efeitos adversos , Dermoscopia/métodos , Epiderme/patologia , Epiderme/virologia , Humanos , Masculino , Infecções por Papillomavirus/virologia , Verrugas/virologia
10.
Int J Cancer ; 146(6): 1514-1522, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31173641

RESUMO

The study aim was to describe human papillomavirus (HPV)-attributable cancer burden in Rwanda, according to anogenital cancer site, HPV type, age and HIV status. Tissue specimens of cervical, vulvar, vaginal, penile and anal cancer diagnosed in 2012-2018 were retrieved from three cancer referral hospitals and tested for high-risk (HR) HPV DNA. Cervical cancer represented the majority of cases (598 of 738), of which 96.0% were HR-HPV positive. HPV-attributable fractions in other cancer sites varied from 53.1% in 81 penile, through 76.7% in 30 vulvar, 83.3% in 24 vaginal, up to 100% in 5 anal cases. HPV16 was the predominant HR-HPV type in cervical cancer (55.0%), followed by HPV18 (16.6%) and HPV45 (13.4%). HPV16 also predominated in other cancer sites (60-80% of HR-HPV-attributable fraction). For cervical cancer, type-specific prevalence varied significantly by histology (higher alpha-9 type prevalence in 509 squamous cell carcinoma vs. higher alpha-7 type prevalence in 80 adenocarcinoma), but not between 501 HIV-negative and 97 HIV-positive cases. With respect to types targeted, and/or cross-protected, by HPV vaccines, HPV16/18 accounted for 73%, HPV31/33/45/52/58 for an additional 22% and other HR-HPV types for 5%, of HPV-attributable cancer burden, with no significant difference by HIV status nor age. These data highlight the preventive potential of the ongoing national HPV vaccination program in Rwanda, and in sub-Saharan Africa as a whole. Importantly for this region, the impact of HIV on the distribution of causal HPV types was relatively minor, confirming type-specific relevance of HPV vaccines, irrespective of HIV status.


Assuntos
Neoplasias do Ânus/virologia , Neoplasias dos Genitais Femininos/virologia , Infecções por HIV/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Neoplasias Penianas/virologia , Adulto , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/patologia , Estudos Transversais , Feminino , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/patologia , Genótipo , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Neoplasias Penianas/epidemiologia , Neoplasias Penianas/patologia , Prevalência , Ruanda/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Neoplasias Vaginais/epidemiologia , Neoplasias Vaginais/patologia , Neoplasias Vaginais/virologia , Neoplasias Vulvares/epidemiologia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/virologia
11.
Gynecol Oncol ; 156(1): 203-210, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31757465

RESUMO

OBJECTIVE: Cervical cancer is the fourth most common cause of cancer-related deaths in Asian women, due to its poor prognosis. This study aimed to decipher genomic alteration profiles of a cohort of Japanese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies and their prognostic significance. METHODS: During 2008-2018, 154 cervical cancer patients underwent a potentially curative resection procedure at the National Cancer Center Hospital. Genomic DNA samples were analyzed using Ion AmpliSeq™ Cancer Hotspot Panel v2. Alterations in the copy number of PIK3CA, ERBB2, PTEN, and STK11 were detected using the TaqMan assay. HPV-positive results were confirmed by genomic testing and in situ hybridization assay. RESULTS: The frequency of genomic alterations in PIK3CA (36%), STK11 (16%), PTEN (11%), TP53 (11%), and KRAS (8%) was >5%. KRAS mutations were preferentially detected in patients with adenocarcinomas, and the frequency of PIK3CA mutations in patients with squamous cell carcinomas was higher than that in patients with other histological cancer types. HPV-positive results were observed in 139/154 (90.3%) patients, and TP53 mutants were detected in HPV-negative specimens. In this study, the overall survival of patients with genomic alterations in STK11 was worse than in patients with wild-type STK11 (hazard ratio = 10.6, P = 0.0079) and TCGA dataset (hazard ratio = 2.46, P = 0.029). CONCLUSIONS: More than one-third of Japanese cervical cancer patients exhibit mutations targeted by molecular targeted therapies. We have proposed the prognostic value of STK11 genomic alterations.


Assuntos
Proteínas Serina-Treonina Quinases/genética , Neoplasias do Colo do Útero/genética , Grupo com Ancestrais do Continente Asiático/genética , Análise Mutacional de DNA , DNA de Neoplasias/genética , DNA de Neoplasias/isolamento & purificação , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/enzimologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Proteínas Serina-Treonina Quinases/metabolismo , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
12.
Virchows Arch ; 476(2): 251-260, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31754816

RESUMO

In rare cases, equivocal histomorphology ('deceiving dysplasia') does not allow immediate diagnosis of cervical high-grade squamous intraepithelial lesion (HSIL). We studied whether these cases are correlated with specific high-risk human papillomavirus (hr HPV) types. During 2011-2017, 39 cases of p16-positive cervical tissue biopsies with unusual ('deceiving') dysplastic histomorphology were identified and matched with the same number of controls (typical HSIL samples). Histomorphological characteristics were reviewed blindly and HPV testing was performed using the clinically validated RealTime test (Abbott) and Anyplex HPV 28 (Seegene). HPV 16 and HPV 31 were the two most frequent HPV types in both groups, although minimum, proportional, hierarchical and any etiological attribution estimates for HPV 16 were significantly lower in the deceiving group (13.2%, 21.3%, 23.7% and 23.7%) than in the control group (32.4%, 48.1%, 48.6% and 48.6%). In addition, the distribution of other hr HPV types differed between the two study groups, with five HPV types (HPV 56, 58, 59, 73 and 82) detected only in the deceiving group. Histomorphologic review of both groups (regardless of HPV type) confirmed significant differences in nuclear atypia, maximum lesion thickness and cellularity, although these were diminished when cross-comparisons between HPV16/18 and non-HPV16/18 cases pooled from both study groups were evaluated. Different attribution estimates for HPV 16, HPV 16/18 and non-16/18 hr HPV types in deceiving and control groups were observed, in particular for HPV 16. However, an unusual (deceiving) histomorphology may also depend on unknown HPV-related molecular changes.


Assuntos
Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Papillomavirus Humano 16/patogenicidade , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/patologia , Detecção Precoce de Câncer/métodos , Feminino , Papillomavirus Humano 18/patogenicidade , Humanos , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , /virologia , Neoplasias do Colo do Útero/virologia
13.
BJOG ; 127(2): 171-180, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237400

RESUMO

BACKGROUND: Persistent infection with high-risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of the vaginal microbiota, infection with human papillomavirus (HPV) and progression to cervical dysplasia and cancer. OBJECTIVE: To assess how specific cervico-vaginal microbiota compositions are associated with HPV infection, cervical dysplasia and cancer, we conducted a systematic review and network meta-analysis (registered in PROSPERO: CRD42018112862). SEARCH STRATEGY: PubMed, Web of science, Embase and Cochrane database. SELECTION CRITERIA: All original studies describing at least two community state types of bacteria (CST), based on molecular techniques enabling identification of bacteria, and reporting the association with HPV infection, cervical dysplasia and/or cervical cancer. DATA COLLECTION AND ANALYSIS: For the meta-analysis, a network map was constructed to provide an overview of the network relationships and to assess how many studies provided direct evidence for the different vaginal microbiota compositions and HPV, cervical dysplasia or cancer. Thereafter, the consistency of the model was assessed, and forest plots were constructed to pool and summarise the available evidence, presenting odds ratios and 95% confidence intervals. MAIN RESULTS: Vaginal microbiota dominated by non-Lactobacilli species or Lactobacillus iners were associated with three to five times higher odds of any prevalent HPV and two to three times higher for high-risk HPV and dysplasia/cervical cancer compared with Lactobacillus crispatus. CONCLUSIONS: These findings suggest an association between certain bacterial community types of the vaginal microbiota and HPV infection and HPV-related disease. This may be useful for guiding treatment options or serve as biomarkers for HPV-related disease. TWEETABLE ABSTRACT: This network meta-analysis suggests an association between different vaginal bacterial community types and the risk of HPV.


Assuntos
Neoplasia Intraepitelial Cervical/patologia , Lactobacillus/fisiologia , Microbiota/fisiologia , Papillomaviridae/fisiologia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , Vagina/patologia , Neoplasia Intraepitelial Cervical/microbiologia , Feminino , Humanos , Metanálise em Rede , Infecções por Papillomavirus/microbiologia , RNA Ribossômico 16S , Neoplasias do Colo do Útero/microbiologia , Neoplasias do Colo do Útero/virologia , Vagina/microbiologia , Vagina/virologia
14.
Int J Cancer ; 146(2): 305-320, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31566705

RESUMO

Cervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well controlled; however, if the inflammation is excessive or it becomes of chronic duration, it can produce detrimental effects. HPV proteins are involved, both directly and indirectly, in the development of chronic inflammation, which is a causal factor in the development of CC. However, other factors may also have a potential role in stimulating chronic inflammation. MicroRNAs (miRNAs) (a class of noncoding RNAs) are strong regulators of gene expression. They have emerged as key players in several biological processes, including inflammatory pathways. Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC. Exosomes are a subset of extracellular vesicles shed by almost all types of cells, which can function as cargo transfer vehicles. Exosomes contain proteins and genetic material (including miRNAs) derived from their parent cells and can potentially affect recipient cells. Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC.


Assuntos
Exossomos/imunologia , Inflamação/imunologia , MicroRNAs/metabolismo , Infecções por Papillomavirus/imunologia , Neoplasias do Colo do Útero/imunologia , Feminino , Regulação da Expressão Gênica/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inflamação/patologia , Inflamação/virologia , Papillomaviridae/imunologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Proteínas Virais/imunologia , Proteínas Virais/metabolismo
15.
Int J Cancer ; 146(2): 461-474, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31603527

RESUMO

The malignant growth of human papillomavirus (HPV)-positive cancer cells is dependent on the continuous expression of the viral E6/E7 oncogenes. Here, we examined the effects of iron deprivation on the phenotype of HPV-positive cervical cancer cells. We found that iron chelators, such as the topical antifungal agent ciclopirox (CPX), strongly repress HPV E6/E7 oncogene expression, both at the transcript and protein level. CPX efficiently blocks the proliferation of HPV-positive cancer cells by inducing cellular senescence. Although active mTOR signaling is considered to be critical for the cellular senescence response towards a variety of prosenescent agents, CPX-induced senescence occurs under conditions of severely impaired mTOR signaling. Prolonged CPX treatment leads to p53-independent Caspase-3/7 activation and induction of apoptosis. CPX also eliminates HPV-positive cancer cells under hypoxic conditions through induction of apoptosis. Taken together, these results show that iron deprivation exerts profound antiviral and antiproliferative effects in HPV-positive cancer cells and suggest that iron chelators, such as CPX, possess therapeutic potential as HPV-inhibitory, prosenescent and proapoptotic agents in both normoxic and hypoxic environments.


Assuntos
Ciclopirox/farmacologia , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas Oncogênicas Virais/antagonistas & inibidores , Proteínas E7 de Papillomavirus/antagonistas & inibidores , Infecções por Papillomavirus/tratamento farmacológico , Proteínas Repressoras/antagonistas & inibidores , Neoplasias do Colo do Útero/tratamento farmacológico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Apoptose/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Ciclopirox/uso terapêutico , Proteínas de Ligação a DNA/metabolismo , Feminino , Células HCT116 , Células HeLa , Humanos , Quelantes de Ferro/farmacologia , Quelantes de Ferro/uso terapêutico , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Proteínas Repressoras/metabolismo , Esferoides Celulares , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
16.
J Cancer Res Clin Oncol ; 146(4): 925-933, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31858242

RESUMO

PURPOSE: Cervical metastasis from unknown primary (CUP) is commonly classified as an advanced overall stage. P16 or human papillomavirus (HPV) positivity in metastatic lymph nodes (LN) might be associated with a favorable survival outcome of CUP. Therefore, we evaluated the prognostic values of p16 immuno-positivity in LN and other clinicopathological factors in patients with squamous cell carcinoma CUP (SCCUP). METHODS: This study involved 83 patients who underwent therapeutic neck dissection and panendoscopic examination and biopsy for suspected CUP. P16 immunostaining and HPV typing in LN were performed in 56 patients. Cox proportional hazard regression analyses were used to identify factors associated with overall survival (OS) and disease-free survival (DFS). RESULTS: Postoperatively, primary tumors (PT) were found in 32 (38.6%) patients, mainly (90.6%) in the oropharynx, and not found in 51 (61.4%) patients. The clinicopathological data (except for histological grade) and 5-year OS and DFS rates did not significantly differ between patients with and without PT identification (all P > 0.05). P16 positivity was associated with favorable OS and DFS outcomes in the patients with PT (P < 0.05) but not in those without PT (P > 0.1). Multivariate analyses showed that age (> 60 years) and LN ratio (≥ 0.1) were the independent predictors of OS and DFS outcomes (all P < 0.05). P16 positivity or other factors were not independent factors. CONCLUSION: Age and LN ratio are significant risk factors of survival and recurrence after primary surgery for SCCUP. Prognostic significance of LN p16 positivity should be further studied.


Assuntos
Neoplasias de Cabeça e Pescoço/secundário , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Imuno-Histoquímica , Linfonodos/patologia , Linfonodos/virologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Recidiva Local de Neoplasia , Neoplasias Primárias Desconhecidas/metabolismo , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prognóstico , Estudos Retrospectivos
17.
Int J Gynecol Pathol ; 39(1): 93-96, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30480645

RESUMO

Epidermolytic acanthoma is a rare benign lesion that most often presents as a solitary or multiple small papular lesions on the trunk, face, limbs or external male genitalia. Only a small number of cases have been reported occurring on the vulva and clinically and histologically they may mimic and be misdiagnosed as viral warts. We report 2 cases of multiple epidermolytic acanthomas localized to the vulva. Molecular tests (in situ hybridization and polymerase chain reaction) showed no evidence of human papillomavirus infection and p16 staining was negative. We stress the need for pathologists to consider epidermolytic acanthoma in the differential diagnosis of multiple vulval lesions resembling viral warts.


Assuntos
Acantoma/diagnóstico por imagem , Hiperceratose Epidermolítica/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Vulvares/diagnóstico por imagem , Verrugas/diagnóstico por imagem , Acantoma/genética , Acantoma/patologia , Diagnóstico Diferencial , Feminino , Genótipo , Humanos , Hiperceratose Epidermolítica/genética , Hiperceratose Epidermolítica/patologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico por imagem , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Vulvares/genética , Neoplasias Vulvares/patologia , Verrugas/genética , Verrugas/patologia
18.
PLoS One ; 14(12): e0226261, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31841543

RESUMO

BACKGROUND: After the early detection of cervical intraepithelial neoplasia (CIN), medical surveillance of the precancerous lesions is carried out to control risk factors to avoid the development of cervical cancer. OBJECTIVE: To explore the effects of medical surveillance on the personal and social lives of women undergoing CIN follow-up and treatment. METHODOLOGY: A generic qualitative study using a poststructuralist perspective of risk management was carried out in a gynecology clinic in a public hospital of the Galician Health Care System (Spain). Participants were selected through purposive sampling. The sample consisted of 21 women with a confirmed diagnosis of CIN. Semistructured interviews were recorded and transcribed, and a thematic analysis was carried out, including researcher triangulation to verify the results of the analysis. FINDINGS: Two main themes emerged from the participants' experiences: CIN medical surveillance encounters and risk management strategies are shaped by the biomedical discourse, and the effects of "risk treatment" for patients include (a) profound changes expected of patients, (b) increased patient risk management, and (c) resistance to risk management. While doctors' surveillance aimed to prevent the development of cervical cancer, women felt they were sick because they had to follow strict recommendations over an unspecified period of time and live with the possibility of a life-threatening disease. Clinical risk management resulted in the medicalization of women's personal and social lives and produced great uncertainty. CONCLUSIONS: This study is the first to conceptualize CIN medical surveillance as an illness experience for patients. It also problematizes the effects of preventative practices in women's lives. Patients deal with great uncertainty, as CIN medical surveillance performed by gynecologists simultaneously trivializes the changes expected of patients and underestimates the effects of medical recommendations on patients' personal wellbeing and social relations.


Assuntos
Neoplasia Intraepitelial Cervical , Medicalização , Aceitação pelo Paciente de Cuidados de Saúde , Percepção , Vigilância da População , Neoplasias do Colo do Útero , Adulto , Idoso , Atitude Frente a Saúde , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/psicologia , Neoplasia Intraepitelial Cervical/terapia , Continuidade da Assistência ao Paciente/normas , Progressão da Doença , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/psicologia , Feminino , Seguimentos , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/psicologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Padrões de Prática Médica/normas , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/psicologia , Lesões Pré-Cancerosas/terapia , Fatores de Risco , Gestão de Riscos/métodos , Gestão de Riscos/normas , Comportamento Social , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/psicologia , Neoplasias do Colo do Útero/terapia , Adulto Jovem
19.
Acta Med Port ; 32(12): 776-781, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31851887

RESUMO

Over the last few decades, behavioral changes in sexual practices have made oral transmission of traditional sexually transmissible infections increasingly recognized. Patients harboring a sexually transmissible infection may first present lesions on the oral cavity, as these may be visible and interfere with basic functions such as speech or swallowing. Moreover, the oral cavity may function as a reservoir for future spread of these infections. In order to successfully control this problem, a greater focus on oral sex should be persued, along with promotion of the use of condom and education on safe oral sex practices. Furthermore, examination of the oral cavity should is essential when evaluating any patient suspected of harboring a sexually transmissible infection. In this article, oral transmission of several viral and bacterial infections is reviewed, including human papillomavirus infection, genital herpes, syphilis and gonorrhea, among others.


Assuntos
Doenças da Boca/complicações , Sexo Seguro , Comportamento Sexual , Doenças Sexualmente Transmissíveis/transmissão , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/transmissão , Chlamydia trachomatis , Gonorreia/diagnóstico , Gonorreia/transmissão , Infecções por HIV/diagnóstico , Infecções por HIV/patologia , Infecções por HIV/transmissão , Herpes Simples/diagnóstico , Herpes Simples/transmissão , Humanos , Doenças da Boca/diagnóstico , Doenças da Boca/patologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/transmissão , Doenças Sexualmente Transmissíveis/diagnóstico , Doenças Sexualmente Transmissíveis/patologia , Sífilis/diagnóstico , Sífilis/patologia , Sífilis/transmissão
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 666-671, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762235

RESUMO

OBJECTIVE: To explore the dynamic changes of human papillomavirus (HPV) type 16 E5 gene in the development of cervical cancer and the significance of E5 mRNA in early screening of cervical cancer. METHODS: Paraffin specimens of cervical lesions were collected from 49 cases (HPV positive) during September 2015 to December 2017 According to the standard of FIGO, all cervical lesions were diagnosed as: 13 cases of cervicitis, cervical intraepithelial neoplasia disorders (CIN) Ⅰ in 5 cases, CIN Ⅱ in 18 cases, CIN Ⅲ in 5 cases, 8 cases of cervical cancer. Real-time fluorescence quantitative PCR was used to detect the integrity of E5 gene and the mRNA expression levels of E5, E6 and E 7in cervical tissues. RESULTS: All the 49 cases showed positive HPV16 infection. E5 genetic integrity in CINⅠwas higher than that in cervical inflammation, CIN Ⅱand cervical cancer (P < 0.05), which was also higher than that in CIN Ⅲ, but without statistically significance (P>0.05). The mRNA levels of E5, E6, E7 were the highest in CIN Ⅲ. Compared with E6 and E7, E5 presented superior expression in all types of cervical lesions (P < 0.05), while E 6and E7 mRNA expressions only increased in CIN Ⅲ and cervical cancer. CONCLUSION: In the patients with HPV16 infection, the integrity of E5 gene in cervical tissues may be related to the occurrence and development of cervical diseases. E5 gene is expected to be the target gene for early screening of cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/virologia , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia , Neoplasia Intraepitelial Cervical/patologia , Feminino , Papillomavirus Humano 16 , Humanos , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia
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