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1.
Acta Cytol ; 64(1-2): 63-70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30889579

RESUMO

The association between high-risk genotypes of human papillomavirus (hr-HPV) and cervical cancer is well established. As hr-HPV testing is rapidly becoming a part of routine cervical cancer screening, either in conjunction with cytology or as primary testing, the management of hr-HPV-positive women has to be tailored in a way that increases the detection of cervical abnormalities while decreasing unnecessary colposcopic biopsies or other invasive procedures. In this review, we discuss the overall utility and strategies of hr-HPV testing, as well as the advantages and limitations of potential triage strategies for hr-HPV-positive women, including HPV genotyping, p16/Ki-67 dual staining, and methylation assays.


Assuntos
Citodiagnóstico/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Detecção Precoce de Câncer/métodos , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/fisiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Triagem , Neoplasias do Colo do Útero/complicações
2.
Acta Cytol ; 64(1-2): 155-165, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30982025

RESUMO

The Papanicolaou (PAP) test is widely used to screen for cervical cancer. All high-grade lesions such as atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), and high-grade squamous intraepithelial lesion, identified on a PAP test should be followed-up by a confirmatory cervical biopsy. In this review, we discuss the challenges in interpreting cervical tissue specimens and the various ancillary techniques used in the evaluation of cervical dysplasia. Ancillary studies include deeper levels, p16 immunohistochemistry (IHC), human papillomavirus (HPV) testing, and, importantly, cyto-histologic correlation. Of these, p16 IHC is consistently sensitive and specific for detecting HSIL. HPV RNA in situ hybridization (ISH) is a newer technique with excellent sensitivity and specificity for detecting virally infected cells and it may be more broadly applicable to both low- and high-grade squamous intraepithelial lesions.


Assuntos
Células Escamosas Atípicas do Colo do Útero/patologia , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Biópsia , Neoplasia Intraepitelial Cervical/diagnóstico , Curetagem , Feminino , Humanos , Teste de Papanicolaou/métodos , Papillomaviridae/fisiologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/diagnóstico
3.
Acta Cytol ; 64(1-2): 30-39, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30783052

RESUMO

Human papilloma virus (HPV)-related squamous cell carcinoma (SCC) is biologically unique and has a better prognosis than conventional SCC of the head and neck. p16 immunohistochemistry emerged as a valuable surrogate marker for HPV in oropharyngeal SCC. The criteria for a positive p16 result in tissue specimens are well established. However, there is no consensus regarding interpreting p16 staining in cell blocks and other cytology specimens. This review discusses the current evidence on p16 testing in cytology specimens and also highlights other methods for HPV testing, including DNA and RNA in situ hybridization, as well as other molecular HPV tests.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Imuno-Histoquímica/métodos , Infecções por Papillomavirus/metabolismo , Biópsia por Agulha Fina/métodos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hibridização In Situ/métodos , Papillomaviridae/genética , Papillomaviridae/fisiologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Sensibilidade e Especificidade
4.
BJOG ; 127(2): 182-192, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31749298

RESUMO

OBJECTIVE: Characterise the vaginal metabolome of cervical HPV-infected and uninfected women. DESIGN: Cross-sectional. SETTING: The Center for Health Behavior Research at the University of Maryland School of Public Health. SAMPLE: Thirty-nine participants, 13 categorised as HPV-negative and 26 as HPV-positive (any genotype; HPV+ ), 14 of whom were positive with at least one high-risk HPV strain (hrHPV). METHOD: Self-collected mid-vaginal swabs were profiled for bacterial composition by 16S rRNA gene amplicon sequencing, metabolites by both gas and liquid chromatography mass spectrometry, and 37 types of HPV DNA. MAIN OUTCOME MEASURES: Metabolite abundances. RESULTS: Vaginal microbiota clustered into Community State Type (CST) I (Lactobacillus crispatus-dominated), CST III (Lactobacillus iners-dominated), and CST IV (low-Lactobacillus, 'molecular-BV'). HPV+ women had higher biogenic amine and phospholipid concentrations compared with HPV- women after adjustment for CST and cigarette smoking. Metabolomic profiles of HPV+ and HPV- women differed in strata of CST. In CST III, there were higher concentrations of biogenic amines and glycogen-related metabolites in HPV+ women than in HPV- women. In CST IV, there were lower concentrations of glutathione, glycogen, and phospholipid-related metabolites in HPV+ participants than in HPV- participants. Across all CSTs, women with hrHPV strains had lower concentrations of amino acids, lipids, and peptides compared with women who had only low-risk HPV (lrHPV). CONCLUSIONS: The vaginal metabolome of HPV+ women differed from HPV- women in terms of several metabolites, including biogenic amines, glutathione, and lipid-related metabolites. If the temporal relation between increased levels of reduced glutathione and oxidised glutathione and HPV incidence/persistence is confirmed in future studies, anti-oxidant therapies may be considered as a non-surgical HPV control intervention. TWEETABLE ABSTRACT: Metabolomics study: Vaginal microenvironment of HPV+ women may be informative for non-surgical interventions.


Assuntos
Metaboloma , Microbiota , Infecções por Papillomavirus/microbiologia , Vagina/microbiologia , Adulto , Estudos Transversais , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactobacillus , Microbiota/genética , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , RNA Ribossômico 16S/genética , Vagina/virologia
5.
J Clin Pathol ; 73(1): 30-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31315894

RESUMO

AIMS: The purpose of the present study was to elucidate the presence of human herpesvirus 6A (HHV-6A), HHV-6B and HHV-7 in samples of the uterine cervix through detection of viral DNA. We analysed normal tissues, samples with low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). We correlated the presence of HHV-6 and HHV-7 with the finding of human papillomavirus (HPV) in mucosal samples. METHODS: Cervical samples were examined and grouped as follows: group 1 (n=29), normal cytology; group 2 (n=61), samples with LSIL; group 3 (n=35), samples with HSIL. Molecular biology examinations were performed in all samples to detect HHV-6, HHV-7 and HPV DNA and to typify HHV-6 species. RESULTS: Group 1: normal cytology and HPV (-): HHV-6: 6.8% (2/29), HHV-7: 79.3% (23/29); group 2: LSIL and HPV (-): HHV-6: 93.1% (27/29), HHV-7: 96.5% (28/29); LSIL and HPV (+): HHV-6: 0% (0/32), HHV-7: 90.6% (29/32); group 3: HSIL and HPV (-): HHV-6: 20% (2/10), HHV-7: 70% (7/10); HSIL HPV (+): HHV-6: 12% (3/25), HHV-7: 68% (17/25). HHV-6A DNA was not detected in any samples. CONCLUSIONS: (1) Both HHV-6 and HHV-7 infect the mucosal cells of the cervix with higher prevalence of HHV-7. (2) The higher prevalence of HHV-6 in LSIL HPV (-) samples compared with those with normal cytology indicates that it constitutes a possible risk factor for atypia production. (3) The presence of HHV-7 in all samples questions its role in the production of atypia. (4) The finding of HHV-6 and HHV-7 suggests that the cervical mucosa is a possible transmission pathway for these viruses.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , DNA Viral/genética , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , Técnicas de Diagnóstico Molecular , Infecções por Roseolovirus/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Argentina , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/virologia , Feminino , Testes de DNA para Papilomavírus Humano , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Infecções por Roseolovirus/genética , Infecções por Roseolovirus/transmissão , Infecções por Roseolovirus/virologia , Lesões Intraepiteliais Escamosas Cervicais/genética , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Adulto Jovem
6.
Int J Cancer ; 146(3): 617-626, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30861114

RESUMO

US guidelines recommend that most women older than 65 years cease cervical screening after two consecutive negative cotests (concurrent HPV and cytology tests) in the previous 10 years, with one in the last 5 years. However, this recommendation was based on expert opinion and modeling rather than empirical data on cancer risk. We therefore estimated the 5-year risks of cervical precancer (cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ [CIN3]) after one, two and three negative cotests among 346,760 women aged 55-64 years undergoing routine cotesting at Kaiser Permanente Northern California (2003-2015). Women with a history of excisional treatment or CIN2+ were excluded. No woman with one or more negative cotests was diagnosed with cancer during follow-up. Five-year risks of CIN3 after one, two, and three consecutive negative cotests were 0.034% (95% CI: 0.023%-0.046%), 0.041% (95% CI: 0.007%-0.076%) and 0.016% (95% CI: 0.000%-0.052%), respectively (ptrend < 0.001). These risks did not appreciably differ by a positive cotest result prior to the one, two or three negative cotest(s). Since CIN3 risks after one or more negative cotests were significantly below a proposed 0.12% CIN3+ risk threshold for a 5-year screening interval, a longer screening interval in these women is justified. However, the choice of how many negative cotests provide sufficient safety against invasive cancer over a woman's remaining life represents a value judgment based on the harms versus benefits of continued screening. Ideally, this guideline should be informed by longer-term follow-up given that exiting is a long-term decision.


Assuntos
Adenocarcinoma in Situ/epidemiologia , Neoplasia Intraepitelial Cervical/epidemiologia , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Adenocarcinoma in Situ/diagnóstico , Adenocarcinoma in Situ/patologia , California/epidemiologia , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , Detecção Precoce de Câncer/normas , Feminino , Humanos , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Guias de Prática Clínica como Assunto , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Estudos Prospectivos , Medição de Risco/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia
7.
Int J Cancer ; 146(3): 810-818, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30980692

RESUMO

Primary prevention through the use of human papillomavirus (HPV) vaccination is expected to impact both cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS). While CIN is well described, less is known about the epidemiology of AIS, a rare cervical precancer. We identified AIS and CIN grade 3 (CIN3) cases through population-based surveillance, and analyzed data on HPV types and incidence trends overall, and among women screened for cervical cancer. From 2008 to 2015, 470 AIS and 6,587 CIN3 cases were identified. The median age of women with AIS was older than those with CIN3 (35 vs. 31 years; p < 0.01). HPV16 was the most frequently detected type in both AIS and CIN3 (57% in AIS; 58% in CIN3), whereas HPV18 was the second most common type in AIS and less common in CIN3 (38% vs. 5%; p < 0.01). AIS lesions were more likely than CIN3 lesions to be positive for high-risk types targeted by the bivalent and quadrivalent vaccines (HPV16/18, 92% vs. 63%; p < 0.01), and 9-valent vaccine (HPV16/18/31/33/45/52/58, 95% vs. 87%; p < 0.01). AIS incidence rates decreased significantly in the 21-24 year age group (annual percent change [APC] overall: -22.1%, 95% CI: -33.9 to -8.2; APC among screened: -16.1%, 95% CI: -28.8 to -1.2), but did not decrease significantly in any older age group. This report on the largest number of genotyped AIS cases to date suggests an important opportunity for vaccine prevention of AIS, and is the first to document a decline in AIS incidence rates among young women during the vaccine era.


Assuntos
Adenocarcinoma in Situ/epidemiologia , Neoplasia Intraepitelial Cervical/epidemiologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Adenocarcinoma in Situ/prevenção & controle , Adenocarcinoma in Situ/virologia , Adolescente , Adulto , Fatores Etários , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , DNA Viral/isolamento & purificação , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Incidência , Programas de Rastreamento/estatística & dados numéricos , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/uso terapêutico , Lesões Pré-Cancerosas/prevenção & controle , Lesões Pré-Cancerosas/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem
8.
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
9.
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
10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(11): 1439-1444, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31838818

RESUMO

Objective: To understand the infection rate and genotype distribution of high risk-human papillomavirus (HR-HPV) and the detection rate of different grades of cervical lesions in Han and Mongolian women in China and provide evidence for the development of screening and vaccination strategies for the prevention and control of cervical cancer in different ethnic groups. Methods: In June 2017, a multicenter, population-based study for cervical cancer screening in low-resource settings in China was conducted in three rural areas: Xiangyuan and Yangcheng counties in Shanxi province, and Etuoke county in Inner Mongolia Autonomous Region. A total of 9 517 women aged 30-65 years were included in the study, and two cervical and vaginal secretion samples were collected from them for HPV and PCR-based HPV DNA tests. The positive samples in any of two tests were used for PCR-based HPV genotyping test by using Sansure-pioneered One-Step Fast Release technology. Women with positive results in any the HPV tests were referred for colposcopy and punch biopsy was given if cervical intraepithelial neoplasia lesion (low-grade lesion or worse) was suspected in colposcopy evaluation. Endocervical curettage was performed if women had an unsatisfactory colposcopy exam (the squamocolumnar junction was not completely visible). Pathological detection result was used as the golden standard of diagnosis. Results: HR-HPV infection rates in Han and Mongolian women were 21.83% (1 842/8 438) and 24.93% (269/1 079), respectively. There were statistical differences in HPV infection rates between the two ethnic groups (χ(2)=5.328, P=0.021). The detection rate of cervical intraepithelial neoplasia grade 1 in Mongolian women (2.83%) was higher than that in Han women (0.87%), and the difference was statistically significant (χ(2)=33.509, P<0.001). There were no significant differences in cervical intraepithelial neoplasia grade 2 or worse detection rate between the two ethnic groups [Mongolian woman: 1.04% (11/1 059), Han Woman: 0.95% (80/8 378), χ(2)=0.069, P=0.793]. Among Han and Mongolian women with cervical intraepithelial neoplasia grade 2 or worse, the three most common HR-HPV types were HPV16, HPV52 and HPV58. There was no significant difference for multiple infection rate between Han and Mongolian women (41.37% vs. 44.35%, χ(2)=0.764, P=0.382). Conclusions: The results show that HPV infection rate in Mongolian women was higher than that in Han women. Close attention should be paid to HPV16, 52 and 58 in the prevention and control of cervical cancer in Han and Mongolian women.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , China/epidemiologia , Colposcopia , Detecção Precoce de Câncer , Feminino , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Papillomaviridae/classificação , Infecções por Papillomavirus/etnologia , Infecções por Papillomavirus/genética , Reação em Cadeia da Polimerase , Vigilância da População , Lesões Pré-Cancerosas/etnologia , Lesões Pré-Cancerosas/genética , Gravidez , Prevalência , Neoplasias do Colo do Útero/etnologia , Neoplasias do Colo do Útero/genética
11.
Emerg Microbes Infect ; 8(1): 1721-1733, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31769733

RESUMO

Human papillomavirus type 6 (HPV6) is the major etiologic agent of genital warts and recurrent respiratory papillomatosis. Although the commercial HPV vaccines cover HPV6, the neutralization sites and mode for HPV6 are poorly understood. Here, we identify the HPV6 neutralization sites and discriminate the inhibition of virus attachment and entry by three potent neutralizing antibodies (nAbs), 5D3, 17D5, and 15F7. Mutagenesis assays showed that these nAbs predominantly target surface loops BC, DE, and FG of HPV6 L1. Cryo-EM structures of the HPV6 pseudovirus (PsV) and its immune complexes revealed three distinct binding modalities - full-occupation-bound to capsid, top-center-bound-, and top-rim-bound to pentamers - and illustrated a structural atlas for three classes of antibody-bound footprints that are located at center-distal ring, center, and center-proximal ring of pentamer surface for 5D3, 17D5, and 15F7, respectively. Two modes of neutralization were identified: mAb 5D3 and 17D5 block HPV PsV from attaching to the extracellular matrix (ECM) and the cell surface, whereas 15F7 allows PsV attachment but prohibits PsV from entering the cell. These findings highlight three neutralization sites of HPV6 L1 and outline two antibody-mediated neutralization mechanisms against HPV6, which will be relevant for HPV virology and antiviral inhibitor design. HighlightsMajor neutralization sites of HPV6 were mapped on the pseudovirus cryo-EM structuremAb 15F7 binds HPV6 capsid with a novel top-rim binding modality and confers a post-attachment neutralizationmAb 17D5 binds capsid in top-centre manner but unexpectedly prevents virus from attachment to cell surface.


Assuntos
Papillomavirus Humano 6/fisiologia , Infecções por Papillomavirus/virologia , Ligação Viral , Internalização do Vírus , Animais , Anticorpos Neutralizantes/análise , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/análise , Anticorpos Antivirais/imunologia , Epitopos/genética , Epitopos/imunologia , Papillomavirus Humano 6/genética , Papillomavirus Humano 6/imunologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Infecções por Papillomavirus/imunologia
12.
BMC Infect Dis ; 19(1): 930, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684884

RESUMO

BACKGROUND: The potential HPV transmission route includes horizontal transmission "in utero" and vertical transmission from parents. Less is known about the role of child's father as a potential source of HPV infection and involved in the pathogen's epidemic chain. A possible consequence of perinatal infection includes HPV-related childhood diseases and carrying the risk of cervical cancer development in female offspring. In view of the evidence, studies of HPV co-occurrence in one or both parents and their offspring seem vital for the implementation of respective preventive measures. Consequently, the aim of this study was to determine the incidence of common HPV 16/18 infections in newborns and their parents, and to assess its role of the periconceptional transmission. METHODS: To determine the incidence of common HPV infections in newborns from single pregnancies and their parents. The study included 146 pregnant women, as well as their partners, and newborns. They were tested for the presence of HPV 16/18 DNA using the PCR method. HPV types 16 and/or 18 were identified using type-specific PCR primers. The quality of the extracted DNA was evaluated by PCR using PC03/PC04 ß-globin-specific primers. The relationship between the presence of neonatal and parental HPV infection was analyzed using a multivariable regression model. Calculations were carried out with the Statistica 10. RESULTS: The presence of HPV DNA was detected in 19 (13,01%) newborns, 28 (19,18%) mothers, and 20 (13,7%) fathers. The viral DNA was detected in 14 newborns delivered by HPV-positive mothers (OR = 26,08; CI: 8,07-84,31, p < 0.001), 12 descendants of HPV-positive fathers (OR = 22,13; CI: 6,97-70,27, p < 0.001), and 10 children originating from two infected parents (OR = 24,20; CI: 6,84-85,57 p < 0.001). Those findings points to a increase risk of an acquired infection in newborns with HPV-positive parents. CONCLUSION: Our findings suggest the possible role of the periconceptional transmission in the mode of acquired HPV 16/18 infections.


Assuntos
Infecções por Papillomavirus/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Adolescente , Adulto , DNA Viral/sangue , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Incidência , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Masculino , Mães , Infecções por Papillomavirus/virologia , Pais , Polônia/epidemiologia , Reação em Cadeia da Polimerase , Gravidez , Adulto Jovem
13.
BMC Public Health ; 19(1): 1514, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718611

RESUMO

BACKGROUND: Cervical cancer was the fourth most common cancer among women worldwide in 2012 and was the eighth most common cancer in 2014 and the eighth greatest cause of female cancer deaths in Hong Kong in 2015. Human papillomavirus (HPV) vaccination has been clinically documented to have a high efficacy in reducing HPV-related cervical intraepithelial neoplasia incidence. Therefore, receiving vaccination is a crucial public health measure to reduce disease burden. Significant others, such as schools and schoolteachers, have prominent influence in shaping adolescents' health perceptions and behavior. Therefore, the perspective of schools and schoolteachers regarding vaccination can significantly influence students' acceptance and accessibility of the vaccine. However, few studies have analyzed the perceptions of schoolteachers toward HPV vaccination, and even fewer have concerned how schoolteachers' perceptions influence their schools' motivation in implementing school-based HPV vaccination programs. This study was thus conducted to fill this literature gap. METHODS: With a Chinese community as the field site of this study, a qualitative approach of five focus group interviews was conducted with 35 schoolteachers from five primary and eight secondary schools in Hong Kong between July 2014 and January 2015. Thematic content analysis was used for data analysis. RESULTS: Perceptual, institutional, student and parental, and collaborator barriers interacted to discourage the sampled schoolteachers from organizing school-based HPV vaccination programs. Lack of knowledge regarding HPV vaccination, perception of HPV vaccination as inappropriate given the students' age, violation of traditional cultural values, lack of perceived needs and perceived risk, opposition from schools, low priority of HPV vaccination over other health education topics, lack of government support, lack of interest from parents and students, and lack of confidence in implementing organizations, all were the mentioned barriers. CONCLUSIONS: The sampled schoolteachers were demotivated to organize school-based HPV vaccination programs because of their perceptions and various social and cultural factors. As significant influencers of adolescent students, schoolteachers and schools should receive more support and information on organizing school-based HPV vaccination programs in the future.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Papillomaviridae , Infecções por Papillomavirus/prevenção & controle , Professores Escolares , Instituições Acadêmicas , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Neoplasia Intraepitelial Cervical/virologia , Criança , Feminino , Educação em Saúde , Hong Kong/epidemiologia , Humanos , Programas de Imunização , Masculino , Motivação , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus , Pais , Aceitação pelo Paciente de Cuidados de Saúde , Pesquisa Qualitativa , Serviços de Saúde Escolar , Estudantes , Neoplasias do Colo do Útero/virologia , Vacinação , Adulto Jovem
14.
Medicine (Baltimore) ; 98(44): e17800, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689859

RESUMO

RATIONALE: Human papillomavirus (HPV)-related oropharyngeal cancer is becoming more common, the primary cancer AQ4 usually occult and appearing only as cystic cervical lymph node (LN) metastasis. Distinguishing between a benign cystic lesion and cystic LN metastasis is challenging given their similar radiologic and histologic appearances. PATIENT CONCERNS: A 54-year-old man presented with a bulging cystic mass measuring 6.4cm on the right side of neck. DIAGNOSES: Postexcision diagnosis was second branchial cleft cyst. After 2 years, the cystic mass recurred, and HPV-related tonsillar squamous cell carcinoma with cystic metastatic LNs was confirmed after wide tonsillectomy and neck dissection. The previous cystic lesion proved to be a cystic metastatic LN from the same malignancy with additional p16 immunostain. INTERVENTIONS: The patient was treated with adjuvant concurrent chemoradiation therapy. OUTCOMES: The patient was followed up in the outpatient department with no evidence of recurrence after 1 year. LESSONS: When an adult has a cystic mass in the upper neck, we must rigorously exclude it as a cystic metastatic LN of occult HPV-related oropharyngeal cancer. Additional p16 staining might be helpful.


Assuntos
Branquioma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Metástase Linfática/diagnóstico , Neoplasias Císticas, Mucinosas e Serosas/diagnóstico , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Orofaríngeas/diagnóstico , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/virologia , Diagnóstico Diferencial , Humanos , Linfonodos/patologia , Linfonodos/virologia , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Pescoço/virologia , Esvaziamento Cervical , Neoplasias Císticas, Mucinosas e Serosas/secundário , Neoplasias Císticas, Mucinosas e Serosas/virologia , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/virologia , Neoplasias Orofaríngeas/secundário , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Neoplasias Tonsilares/diagnóstico , Neoplasias Tonsilares/patologia , Neoplasias Tonsilares/virologia
15.
Pan Afr Med J ; 33: 284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692869

RESUMO

Introduction: Cervical cancer is the commonest gynaecological malignancy and the second most common cancer among women worldwide. Several epidemiological, clinical and molecular studies have strongly implicated oncogenic high-risk human papillomavirus infection in the aetiopathogenesis of cervical cancer. The objectives of this study were to determine the cervical HPV prevalence and genotype distribution in cervical cancer in Maiduguri, Nigeria. Methods: This was a descriptive and retrospective study. Sixty-three archived paraffin-embedded tissue blocks with confirmed diagnoses of cervical cancer during the study period (2013-2015) were retrieved and examined. The procedure included deparaffinization of tissue samples, DNA extraction, PCR, gel electrophoresis, and HPV genotyping by reverse hybridization line probe assay. Results: Sixty-three cervical cancer cases were subjected to genomic DNA extraction and HPV-DNA detection by PCR. Fifty-eight samples showed PCR positivity while 5 samples were PCR negative. HPV-specific DNA was detected in 44 of the 58 PCR-positive samples and thus the prevalence was 69.8%. Ten different high-risk HPV genotypes were detected. Both single and multiple high-risk HPV infections were observed. The most prevalent type of the human papillomavirus detected was HPV16. Conclusion: HPV-DNA was prevalent in majority of the examined cervical cancer tissues and that HPV16, HPV18, HPV45, HPV51 and HPV52 were the predominant HPVs detected in both single and multiple HPV infections. The results of this study and further studies will provide more detailed information about HPV and may contribute significantly to the prevention of cervical cancer through primary high-risk HPV testing and HPV vaccination against the oncogenic viruses.


Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/patologia , DNA Viral , Feminino , Genótipo , Humanos , Nigéria/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Prevalência , Estudos Retrospectivos , Neoplasias do Colo do Útero/virologia
16.
BMC Public Health ; 19(1): 1529, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729969

RESUMO

BACKGROUND: Human papillomavirus (HPV) has been associated with certain types of oropharyngeal cancers and yet, the level of knowledge that dental professionals and the lay public have in terms of HPV transmission, oral sexual activities, and oral cancer development needs exploration. The aim of this study was to assess the knowledge held by practicing dental professionals as well as the lay public regarding Human Papillomavirus (HPV) transmission through oral sex and subsequent oropharyngeal cancer development. METHODS: Textual data were collected from a public forum with dental professionals in. Vancouver, who discussed the HPV-oral sex-oral cancer triad, and from survey data gathered from 212 lay public participants (also in Vancouver) who answered a 13-item questionnaire on the perceived risks of oral sex in terms of HPV infection and oropharyngeal cancer development. The data were analyzed statistically by age group, gender, and sexual orientation using descriptive statistics, while an ANOVA test was used to compare variation in the responses to the survey (p-value = 0.05). RESULTS: The forum engaged 46 health care professionals, many of whom were aware of the potential risks for head and neck cancer development due to HPV infection, while also questioning "how to effectively talk about HPV with patients." The survey revealed that 34.5% of the participants believed that oral sex is an activity with no or low risk for the transmission of HPV, while 84% of participants believed the same sexual practices were of low or no-risk for HIV (Human Immunodeficiency Virus) transmission. Most participants (82%) never discussed oral sexual activities with their physicians or dentists/dental hygienists. CONCLUSIONS: The general public remains mostly unaware of the potential links between HPV infection and oropharyngeal cancer. Physicians and dental providers should discuss oral sexual practice with their patients to raise awareness.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Neoplasias Bucais/psicologia , Neoplasias Orofaríngeas/psicologia , Infecções por Papillomavirus/psicologia , Comportamento Sexual/psicologia , Adulto , Recursos Humanos em Odontologia/psicologia , Feminino , Infecções por HIV/psicologia , Infecções por HIV/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/virologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Infecções por Papillomavirus/transmissão , Infecções por Papillomavirus/virologia , Inquéritos e Questionários
17.
Braz Oral Res ; 33: e091, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778470

RESUMO

Human Papillomavirus (HPV) has considerable tropism for epithelial and mucosal tissues and can therefore be found in several anatomical sites, including the oral cavity. This study aimed to investigate the presence of HPV-DNA and the most frequent viral types in patients using full dentures, compare to patients not using full dentures and to associate its presence with socio-epidemiological and behavioral factors. The study consisted of 90 patients with or without full dentures at the time of collection, treated at a public dental clinic. The samples were obtained by exfoliating the oral cavity, and analyzed for HPV-DNA using the nested PCR with PGMY09/11 (450-bp), and general primers GP5+/GP6+ (150-bp). Genotyping was performed by specific-type PCR to HPV 6, 11, 16, 18, 31, 33, and 45; and Restriction Fragment Length Polymorphism (RFLP). Pearson's Chi-square test (x 2 ) or Fisher's exact test were applied and significant variables in these tests were analyzed by multinomial logistic regression analysis to estimate odds ratio (OR). HPV-DNA was detected in 27.7% of samples and, among those obtained from patients using full dentures, positivity for HPV-DNA was 41.9% (p = 0.025). The most frequent viral types were low-risk HPV 6 and 11, and high-risk HPV 31 and 45. Patients who used full dentures had an odds ratio of 2.1 to be positive for HPV DNA. Our results indicate the need for periodic dental follow-up of patients with full dentures in order to preserve the basic conditions of oral health, and also to monitor the appearance of lesions with malignant potential.


Assuntos
Prótese Total/virologia , Vírus Oncogênicos/isolamento & purificação , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Carcinogênese , Estudos Transversais , DNA Viral/isolamento & purificação , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/virologia , Infecções por Papillomavirus/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Fatores de Risco , Fatores Socioeconômicos
18.
Artigo em Inglês | MEDLINE | ID: mdl-31738865

RESUMO

This eleventh national annual immunisation coverage report focuses on data for the calendar year 2017 derived from the Australian Immunisation Register (AIR) and the National Human Papillomavirus (HPV) Vaccination Program Register. This is the first report to include data on HPV vaccine course completion in Aboriginal and Torres Strait Islander (Indigenous) adolescents. 'Fully immunised' vaccination coverage in 2017 increased at the 12-month assessment age reaching 93.8% in December 2017, and at the 60-month assessment age reaching 94.5%. 'Fully immunised' coverage at the 24-month assessment age decreased slightly to 89.8% in December 2017, following amendment in December 2016 to require the fourth DTPa vaccine dose at 18 months. 'Fully immunised' coverage at 12 and 60 months of age in Indigenous children reached the highest ever recorded levels of 93.2% and 96.9% in December 2017. Catch-up vaccination activity for the second dose of measles-mumps-rubella-containing vaccine was considerably higher in 2017 for Indigenous compared to non-Indigenous adolescents aged 10-19 years (20.3% vs. 6.4%, respectively, of those who had not previously received that dose). In 2017, 80.2% of females and 75.9% of males aged 15 years had received a full course of three doses of human papillomavirus (HPV) vaccine. Of those who received dose one, 79% and 77% respectively of Indigenous girls and boys aged 15 years in 2017 completed three doses, compared to 91% and 90% of non-Indigenous girls and boys, respectively. A separate future report is planned to present adult AIR data and to assess completeness of reporting.


Assuntos
Programas de Imunização , Imunização , Grupo com Ancestrais Oceânicos/estatística & dados numéricos , Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Cobertura Vacinal , Adolescente , Algoritmos , Relatórios Anuais como Assunto , Austrália/epidemiologia , Pré-Escolar , Estudos de Coortes , Feminino , Serviços de Saúde do Indígena , Humanos , Lactente , Masculino , Infecções por Papillomavirus/virologia , Sistema de Registros
19.
BMC Infect Dis ; 19(1): 842, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615443

RESUMO

BACKGROUND: HPV test implementation as a primary screening tool has the potential to decrease cervical cancer incidence as shown by several studies around the world. However, in many low-resource settings, the HPV test introduction has been backed down mainly due to its price. In this study, we present a novel low-cost strategy involving simple devices and techniques for high-risk human papillomavirus (HR-HPV) detection. The analytical performance to detect HR-HPV infections of this novel strategy was assessed by comparing it with the Hybrid Capture 2 system (HC2), which is used as gold standard. METHODS: Paired-cervical samples were collected from 541 women assisting to gynecological services in an outpatient clinic. One sample was transported in the Hybrid Capture Standard Transport Medium for HR-HPV detection by the HC2. The second sample was transported on glass slide for detection by PCR-based techniques (GP-EIA, BSGP-EIA and pU 1 M-L/2R). RESULTS: The level of agreement between the PCR-based techniques and HC2 system was determined with the Cohen's kappa value. The kappa values between HC2 and GP-EIA, BSGP-EIA and pU 1 M-L/2R were 0.71 (CI 95% 0.63-0.78), 0.78 (CI 95% 0.71-0.84) and 0.63 (CI 95% 0.55-0.72), respectively. However, when the results from both BSGP-EIA and pU 1 M-L/2R were combined, the level of agreement with HC2 was increased to 0.82 (CI 95% 0.76-0.88), reflecting a very good agreement between the two HR-HPV detection strategies. Furthermore, the sensitivity of both techniques combined was also increased compared to the BSGP-EIA (88.7% vs 77.4%) and the pU (88.7 vs 60.9%) without penalizing the specificity obtained with the BSGP-EIA (95.1% vs 96.9%) and the pU (95.1% vs 96.5%). CONCLUSIONS: This novel strategy, combining two PCR-based techniques for HR-HPV detection, could be useful for cervical cancer screening in self-collected samples in low-income countries.


Assuntos
DNA Viral/análise , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da Polimerase/métodos , Neoplasias do Colo do Útero/diagnóstico , Colo do Útero/patologia , DNA Viral/metabolismo , Detecção Precoce de Câncer , Feminino , Genótipo , Humanos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase/economia , Kit de Reagentes para Diagnóstico , Risco , Sensibilidade e Especificidade , Análise de Sequência de DNA , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia
20.
Anal Bioanal Chem ; 411(28): 7451-7460, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31588523

RESUMO

Cervical cancer is the second most common cancer in the world's woman population with a high incidence in developing countries where diagnostic conditions for the cancer are poor. The main culprit causing the cancer is the human papillomavirus (HPV). HPV is divided into three major groups, i.e., high-risk (HR) group, probable high-risk (pHR) group, and low-risk (LR) group according to their potential of causing cervical cancer. Therefore, developing a sensitive, reliable, and cost-effective point-of-care diagnostic method for the virus genotypes in developing countries even worldwide is of high importance for the cancer prevention and control strategies. Here we present a combined method of isothermal recombinase polymerase amplification (RPA), lateral flow dipstick (LFD), and reverse dot blot (RDB), in quick point-of-care identification of HPV genotypes. The combined method is highly specific to HPV when the conserved L1 genes are used as targeted genes for amplification. The method can be used in identification of HPV genotypes at point-of-care within 1 h with a sensitivity of low to 100 fg of the virus genomic DNA. We have demonstrated that it is an excellent diagnostic point-of-care assay in monitoring the disease without time-consuming and expensive procedures and devices.


Assuntos
Southern Blotting/métodos , Genes Virais , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sequência de Aminoácidos , DNA Viral/análise , DNA Viral/normas , Humanos , Limite de Detecção , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Reprodutibilidade dos Testes
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