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1.
Int J Gynecol Cancer ; 30(1): 35-40, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31792083

RESUMO

OBJECTIVE: Triage with HPV genotyping has some caveats and debates for HPV positive cases other than 16 and 18. The Swede score colposcopic scoring system has not previously been evaluated in this group of patients. OBJECTIVE: To use the Swede score colposcopic scoring system to compare scores and final histopathological results in women who have undergone colposcopy owing to infection with high risk-HPVs other than HPV16 and 18 and to establish new cut-off values to predict pre-malignant lesions in this group of patients. METHODS: This study was conducted in 613 women undergoing colposcopic evaluation because of abnormal cervical cytology together with high-risk HPV infection. All patients referred were evaluated by an expert colposcopist, given a Swede score (using the Swede score colposcopic scoring system) by using five variables (acetowhiteness, margins plus surface, vessel pattern, lesion size, and iodine staining), and had at least one biopsy procedure (either colposcopically directed or by a loop electrical excision procedure). Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio values, and receiver operating characteristic curves for each clinico-pathological variable to detect low-grade and high-grade squamous intra-epithelial lesions, and any squamous cell abnormality (low-grade + high-grade squamous intra-epithelial lesions) were evaluated individually. RESULTS: Final histopathological results of the patients were normal in 53.2% of cases, low-grade lesions in 32.5% of cases, and high-grade lesions in 14.4% of cases. Swede score was ≥8 (median 7.97) for high-grade lesions and ≥5 (median 5.06) for low-grade lesions. The area under the curve values (95% CI) of Swede scores for low-grade and high-grade squamous intra-epithelial lesions, and low-grade + high grade lesions were 0.92, 0.98, and 0.96, respectively. A Swede score cut-off value ≥6 had a sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios of 92%, 98%, 93%, 98%, and 50 (22.6 to 110.8), respectively, for high-grade lesions at the final pathology (P<0.001). One high-risk HPV type (except 16 and 18) was no better than another for calculating the median Swede score during colposcopy (P=0.43). CONCLUSIONS: The Swede score colposcopic scoring system appears to be a useful tool for evaluating atypical cervical cytology in women with high-risk HPV infection other than HPV types 16 and 18.


Assuntos
Alphapapillomavirus/isolamento & purificação , Células Escamosas Atípicas do Colo do Útero/patologia , Células Escamosas Atípicas do Colo do Útero/virologia , Neoplasia Intraepitelial Cervical/diagnóstico , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Alphapapillomavirus/classificação , Alphapapillomavirus/genética , Biópsia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Colposcopia , Feminino , Papillomavirus Humano 16/classificação , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/classificação , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/isolamento & purificação , Humanos , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
2.
Arch Virol ; 164(11): 2699-2706, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31435867

RESUMO

Recently, a clinical need for an improved human papilloma virus (HPV) test that covers a broad range of genotypes has emerged as a valuable primary screening tool for cervical lesions. The liquid bead microarray (LBMA) assay is a recently developed high-throughput platform covering a broad range of genotypes. Here, we compared the clinical performance of two recently developed LBMA assays, GeneFinderTM HPV Liquid Bead Microarray (GeneFinder) and CareGENETM HPV genotyping kit-O (CareGENE), in the Korean general population. A total of 3,148 cervical swabs were tested by the GeneFinder and CareGENE assays. Cases with discrepant results between the two assays were subjected to direct sequencing as a reference method for evaluating the performance of the two LBMA assays. Among all swabs tested, 12.6% showed HPV positivity, and the prevalent HPV genotypes were HPV53, 70, 16, 39, and 51, in that order. The concordance rates between the two assays for the detection of HPV and for genotyping were 96.6% (kappa = 0.836) and 94.5% (kappa = 0.779), respectively. The two LBMA assays showed comparable sensitivity and specificity for HPV detection (GeneFinder: sensitivity 94.4% and specificity 98.7%, CareGENE: sensitivity 89.8% and specificity 99.6%) and for genotyping (GeneFinder: sensitivity 91.0% and specificity 96.6%, CareGENE: sensitivity 90.2% and specificity 99.1%). This is the first demonstration that CareGENE has comparable clinical performance to GeneFinder, which has been established to show excellent performance for screening HPV in previous studies. Both LBMA platforms are thus considered to be valuable tools for HPV detection and genotyping to improve cervical screening in the general population.


Assuntos
Alphapapillomavirus/genética , Detecção Precoce de Câncer/métodos , Ensaios de Triagem em Larga Escala/métodos , Análise em Microsséries/métodos , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alphapapillomavirus/classificação , Alphapapillomavirus/isolamento & purificação , Feminino , Técnicas de Genotipagem , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/virologia , Adulto Jovem
3.
Eur J Health Econ ; 20(6): 829-840, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30900047

RESUMO

INTRODUCTION: The objectives of this study were to estimate the economic burden of HPV in Italy, accounting for total direct medical costs associated with nine major HPV-related diseases, and to provide a measure of the burden attributable to HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 infections. METHODS: A cost-of-illness incidence-based model was developed to estimate the incidences and costs of invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, oropharyngeal, anogenital warts, and recurrent respiratory papillomatosis (RRP) in the context of the Italian National Health System (NHS). We used data from hospital discharge records (HDRs) of an Italian region and conducted a systematic literature review to estimate the lifetime cost per case, the number of incident cases, the prevalence of HPV9 types. Costs of therapeutic options not included in the diagnosis-related group (DRG) tariffs were estimated through a scenario analysis. RESULTS: In 2018, the total annual direct costs were €542.7 million, with a range of €346.7-€782.0 million. These costs could increase considering innovative therapies for cancer treatment (range €16.2-€37.5 million). The fraction attributable to the HPV9 genotypes without innovative cancers treatment was €329.5 million, accounting for 61% of the total annual burden of HPV-related diseases in Italy. Of this amount, €135.9 million (41%) was related to men, accounting for 64% of the costs associated with non-cervical conditions. CONCLUSIONS: The infections by HPV9 strains and the economic burden of non-cervical HPV-related diseases in men were found to be the main drivers of direct costs.


Assuntos
Efeitos Psicossociais da Doença , Infecções por Papillomavirus/economia , Doenças do Colo do Útero/economia , Alphapapillomavirus/genética , Alphapapillomavirus/isolamento & purificação , Antineoplásicos Imunológicos/economia , Antineoplásicos Imunológicos/uso terapêutico , Custos e Análise de Custo , Feminino , Hospitalização/economia , Humanos , Itália/epidemiologia , Programas Nacionais de Saúde , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/epidemiologia , Doenças do Colo do Útero/tratamento farmacológico , Doenças do Colo do Útero/epidemiologia , Doenças do Colo do Útero/virologia
4.
Biomark Med ; 13(6): 497-506, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30924676

RESUMO

Objective: This systematic review evaluates the accuracy of mRNA HPV biomarker for the identification of cervical intra-epithelial neoplasia (CIN) or cervical cancer during a follow-up after conization, taking histopathology as reference standard. Methods: A search of electronic databases was performed, for studies published until June 2018. As results, after screening, five studies including 1148 patients met the inclusion criteria. Dichotomization was performed by CIN2+ versus CIN1-. By analyzing all five studies, a sensitivity of 62.4% (95% CI: 54.8-69.7), specificity of 91.9% (95% CI: 90.0-93.5) and area under the curve of 0.5685 were revealed. Conclusion: mRNA HPV assay presents a high specificity and is an adequate tool for cervical cancer screening in the follow-up after conization.


Assuntos
Alphapapillomavirus/genética , Alphapapillomavirus/isolamento & purificação , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Alphapapillomavirus/fisiologia , Feminino , Humanos , RNA Mensageiro/genética , Recidiva , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia
5.
PLoS Pathog ; 15(2): e1007442, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30818369

RESUMO

Persistent expression of high-risk HPV oncogenes is necessary for the development of anogenital and oropharyngeal cancers. Here, we show that E6/E7 expressing cells are hypersensitive to DNA crosslinking agent cisplatin and have defects in repairing DNA interstrand crosslinks (ICL). Importantly, we elucidate how E6/E7 attenuate the Fanconi anemia (FA) DNA crosslink repair pathway. Though E6/E7 activated the pathway by increasing FancD2 monoubiquitination and foci formation, they inhibited the completion of the repair by multiple mechanisms. E6/E7 impaired FancD2 colocalization with double-strand breaks (DSB), which subsequently hindered the recruitment of the downstream protein Rad51 to DSB in E6 cells. Further, E6 expression caused delayed FancD2 de-ubiquitination, an important process for effective ICL repair. Delayed FancD2 de-ubiquitination was associated with the increased chromatin retention of FancD2 hindering USP1 de-ubiquitinating activity, and persistently activated ATR/CHK-1/pS565 FancI signaling. E6 mediated p53 degradation did not hamper the cell cycle specific process of FancD2 modifications but abrogated repair by disrupting FancD2 de-ubiquitination. Further, E6 reduced the expression and foci formation of Palb2, which is a repair protein downstream of FancD2. These findings uncover unique mechanisms by which HPV oncogenes contribute to genomic instability and the response to cisplatin therapies.


Assuntos
Alphapapillomavirus/genética , Reparo do DNA , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Alphapapillomavirus/metabolismo , Cisplatino/farmacologia , Dano ao DNA , Proteína do Grupo de Complementação N da Anemia de Fanconi/metabolismo , Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo , Instabilidade Genômica , Células HEK293 , Humanos , Proteínas Oncogênicas Virais/biossíntese , Proteínas Oncogênicas Virais/genética , Oncogenes , Proteínas E7 de Papillomavirus/biossíntese , Proteínas E7 de Papillomavirus/genética , Cultura Primária de Células , Proteínas Repressoras/biossíntese , Proteínas Repressoras/genética , Transdução de Sinais , Ubiquitinação
6.
J Eur Acad Dermatol Venereol ; 33(7): 1304-1311, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30835882

RESUMO

BACKGROUND: High-risk α-genus human papillomaviruses (α-HPVs) are linked to cervical and genital carcinomas; however, their correlation with cutaneous squamous cell carcinoma (cuSCC) or premalignant skin lesions remains controversial. OBJECTIVE: We evaluated the contribution of high-risk α-HPV to the occurrence of cuSCC, Bowen's disease and actinic keratosis (AK), and the distribution of high-risk α-HPV genotypes in these cutaneous tumours. METHODS: HPV genotypes were determined using a commercial PCR-based microarray on skin tissue samples collected from 76 [38 young (<60 years) and 38 elderly (>60 years)] cuSCC, 34 Bowen's disease, 48 AK patients and 10 young controls. Associations between α-HPV prevalence and relevant risk factors were analysed. RESULTS: High-risk α-HPV was more frequently detected in cuSCC patients (57.9%) than in the patients with Bowen's disease (38.2%), AK (0.0%) and control patients (10.0%). The high-risk α-HPV prevalence was higher in young than in elderly cuSCC patients (65.8% vs. 50.0%, P = 0.031). The most common HPV type was 16, present in 90.9% of all HPV-carrying cuSCC patients. Multiple infections with different high-risk α-HPV types were found in 20.5% of HPV-related cuSCC, whereas only single infection with type 16 was found in Bowen's disease. Although sun exposure is known as a major risk factor for cuSCC, high-risk α-HPVs were more frequently found in non-exposed sites rather than in sun-exposed sites of cuSCC. CONCLUSION: Multiple infections, as well as single infection with high-risk α-HPV may link to cuSCC. In spite of the involvement of high-risk α-HPV at high levels in cuSCC and Bowen's disease, no high-risk α-HPV was detected in AK patients, suggesting that Bowen's disease rather than AK might be involved in the development of HPV-related cuSCC as a precursor.


Assuntos
Alphapapillomavirus/isolamento & purificação , Doença de Bowen/complicações , Ceratose Actínica/complicações , Infecções por Papillomavirus/complicações , Lesões Pré-Cancerosas/complicações , Neoplasias Cutâneas/complicações , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alphapapillomavirus/genética , Face , Feminino , Genitália , Genótipo , Mãos , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Coxa da Perna , Tronco
7.
Sex Transm Infect ; 95(5): 368-373, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30723186

RESUMO

OBJECTIVES: In 2008, a national human papillomavirus (HPV) vaccination programme for females was introduced in England using the bivalent vaccine (HPV16 and 18 only). In 2012, the programme changed to offer the quadrivalent vaccine that includes protection against the two HPV types that cause the majority of anogenital warts (AGW; HPV6 and 11). We present data reporting AGW diagnoses in sexual health clinics (SHCs) in England to the end of 2017, including diagnoses among birth cohorts offered the quadrivalent vaccine. METHODS: Using data from all SHCs across England, we performed ecological analyses to consider rates of AGW diagnoses by age, gender and sexual orientation. We tested for trends over time of diagnoses of AGW in young females, heterosexual males, and men who have sex with men (MSM) between the ages of 15 and 24 years during both bivalent (2009 to 2013) and quadrivalent (2014 to 2017) vaccine time periods using Poisson regression. RESULTS: Between 2014 and 2017, there was strong evidence for a decreasing trend in the rate of AGW diagnoses at SHC among females aged 15-17 years from 257.5 to 45.7 per 100 000 population (82.3% decline) and same aged heterosexual males from 59.1 to 19.1 per 100 000 population (67.7% decline). The reductions in the incidence of AGW diagnoses in MSM aged 15-17 years were less clear (decreased by 13.6% between 2014 and 2017, from 129.9 to 112.2 per 100 000 population). CONCLUSIONS: The moderate, unexpected declines in AGW seen since the introduction of a high-coverage HPV vaccination programme using the bivalent vaccine are being followed, as expected, by much larger declines among females offered the quadrivalent vaccine and same-aged heterosexual males. Surveillance plans are in place to continue to monitor AGW diagnoses to evaluate the impact of both female and targeted MSM HPV vaccination on early disease outcomes.


Assuntos
Alphapapillomavirus/imunologia , Condiloma Acuminado/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Adolescente , Adulto , Alphapapillomavirus/genética , Criança , Condiloma Acuminado/epidemiologia , Condiloma Acuminado/virologia , Inglaterra/epidemiologia , Feminino , Homossexualidade Masculina , Humanos , Masculino , Minorias Sexuais e de Gênero/psicologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Vacinação , Adulto Jovem
8.
Int J Cancer ; 145(6): 1465-1474, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30698281

RESUMO

The prevalence of human papillomavirus (HPV) in squamous cell carcinoma of unknown primary in the head and neck (SCCUPHN), and prognosis by HPV status of SCCUPHN patients has been difficult to estimate because of the rarity of this subtype. In MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, EMBASE, Cochrane library and Web of Science searches, observational studies and clinical trials that reported survival rates of patients with SCCUPHN by HPV status were identified. Meta-analysis estimated the prevalence and prognosis (overall survival, OS; progression-free survival, PFS) of SCCUPHN by HPV status, and compared them to studies of oropharyngeal squamous cell carcinoma (OPSCC) from the same institutions and across continents. In 17 SCCUPHN studies (n = 1,149) and 17 institution-matched OPSCC studies (n = 6,522), the pooled HPV prevalence of SCCUPHN was 49%, which was only 10% (95%CI: 1-19%) lower than OPSCC prevalence in the underlying population. Estimated 5-year OS for HPV-negative SCCUPHN was 44% (95%CI: 36-51%) vs. HPV-positive SCCUPHN of 91% (95%CI: 86-96%); hazard ratio (HR) for OS was 3.25 (95%CI: 2.45-4.31) and PFS was 4.49 (95%CI: 2.88-7.02). HRs by HPV status for OPSCC were similar to that in SCCUPHN. While North American SCCUPHNs had higher HPV prevalence than European SCCUPHNs (OR = 2.68 (95%CI: 1.3-5.6)), HR of OS for HPV-negative vs. HPV-positive patients were similar in both continents (HRs of 3.78-4.09). Prevalence of HPV among SCCUPHN patients were lower than in OPSCC. The survival benefit conferred by being HPV-positive was similar in SCCUPHN as in OPSCCs, independent of continent.


Assuntos
Alphapapillomavirus/isolamento & purificação , Genes p16 , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Primárias Desconhecidas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Alphapapillomavirus/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Neoplasias Primárias Desconhecidas/virologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Análise de Sobrevida
9.
PLoS One ; 14(1): e0211260, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30699172

RESUMO

BACKGROUND: High-risk human papillomavirus (HR-HPV) has been demonstrated to be the necessary cause of cervical carcinoma. High-risk HPV detection has a prognostic significance for the women who are at increased risk of disease progression. HPV genotyping in cervical cancer precursor lesions is crucial for prevention and management of cervical cancer. This study was designed to investigate the distribution of HR-HPV genotypes among a group of patients with high-grade squamous intraepithelial lesions and higher, of the cervix, in Botswana. MATERIALS AND METHODS: 185-archived residual formalin-fixed paraffin-embedded cervical biopsies collected between the years, 2006 and 2008 were studied. These tissues were diagnosed with HSIL (n = 146) and squamous cell carcinoma (n = 39). DNA was extracted using the Abbott m2000 analyser (Abbott Laboratories, Illinois) using reagents provided by the manufacturer. HPV genotyping was done using the Abbott RealTime HR-HPV PCR, which qualitatively detects 14 HR-HPV (reported as HPV 16, 18 & Other HR-HPV). RESULTS: DNA was successfully extracted from 162/185 (87.6%) tissues as indicated by a positive ß-globin test. 132/162 (82%) tested positive for HR-HPV The HPV 16 prevalence was 50% (66/132), HPV 18 at 15.2% (20/132) and other Group 1 HR-HPV plus HPV 66 and 68 had a prevalence of 56.1% (74/132). Other HR-HPV types were common in HSIL than in carcinoma, while HPV 16 was more prevalent in carcinomas than other HR-HPV genotypes. CONCLUSION: In this study, HPV 16 and other HR-HPV genotypes were commonly associated with HSIL but HPV 18 was uncommon among Botswana women. Our data highlights the need for multivalent HPV vaccines with cross coverage for other high risk HPV other than HPV 16 and 18.


Assuntos
Alphapapillomavirus/classificação , Carcinoma de Células Escamosas/virologia , Técnicas de Genotipagem/métodos , Infecções por Papillomavirus/epidemiologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Adulto , Alphapapillomavirus/genética , Biópsia , Botsuana , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Feminino , Humanos , Infecções por Papillomavirus/diagnóstico , Inclusão em Parafina , Prevalência , Prognóstico , Lesões Intraepiteliais Escamosas Cervicais/patologia , Fixação de Tecidos
10.
J Formos Med Assoc ; 118(1 Pt 1): 203-208, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29636296

RESUMO

BACKGROUND: The incidence of HPV positive oropharyngeal cancer is increasing in Taiwan. Given this, it is critical to understand the prevalence of oral HPV infection since this cancer is potentially preventable. A community-based study was conducted to evaluate the prevalence of oral HPV infection and sexual behavior changes. METHODS: Between January and December 2016, 100 subjects between 20 and 70 years-old with current/ever betel nut chewing or current cigarette smoking visited the Department of Health, New Taipei City. Subjects with cancer history or known HIV/AIDS were excluded. Sexual behavior information was collected through a questionnaire. Oral rinse samples and oropharyngeal swabs were obtained for HPV genotyping using the EasyChip HPV genotyping array (King-Car, Taiwan). RESULTS: 92 men and 8 women were recruited. The prevalence of oral HPV infection was 3%, present between 60 and 70 (11%) and between 30 and 40 years old (4%). The prevalence of the first sexual contact at younger than 20 years old were 71.4%, 53.6%, 15.4% and 44% in <40, 40-49, 50-59 and 60+ years old, respectively (p for trend = 0.0036). The prevalence of 3 or more lifetime sexual partners were 60.7%, 57.1%, 23.1% and 16.7%, respectively for <40, 40-49, 50-59 and 60+ years old (p for trend = 0.0005). CONCLUSION: The prevalence of oral HPV infection is 3%, in current/ever betel nut chewers or current cigarette smokers in Northern Taiwan. Younger generation have more lifetime sexual partners and younger first sexual contact. This could explain the rising incidence of HPV positive oropharyngeal cancer in Taiwan.


Assuntos
Areca/efeitos adversos , Fumar Cigarros/efeitos adversos , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/epidemiologia , Adulto , Fatores Etários , Idoso , Alphapapillomavirus/genética , Diagnóstico Bucal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/epidemiologia , Prevalência , Fatores de Risco , Amostragem , Taiwan/epidemiologia , Adulto Jovem
11.
Gene ; 686: 171-176, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30471332

RESUMO

It is well recognized that the association of human papillomavirus (HPV) and cervical carcinogenesis is based on the presence of HPV DNA sequence. The E6 and E7 oncoproteins encoded by high-risk HPV types play a key role in carcinogenesis. HPV58 type accounts for a larger share of cervical disease in China, whereas data on HPV58 genetic variability in China is limited. We aimed to evaluate the diversity of HPV58 genetic variants by sequencing the entire E6 and E7 genes. Phylogenetic trees were constructed by Maximum likelihood method by MEGA 5.05 software. In this study, the overall HPV infection rate was 22.6% (2891/12780) in Southeast China and the prevalence of HPV58 infection rate was 2.6% (335/12780). 26 nucleotides substitutions were observed in E6 and E7 genes with 10 novel substitutions and 17 non-synonymous substitutions. We obtained 25 distinct variation patterns which the accession GenBank numbers as MH348918-MH348942. All of HPV58 variants belong to lineage A, while no lineage B, C and D were detected in Taizhou area, Southeast China. The sublineage A1, A2, and A3 variants were found in 136 (68.3%), 39 (19.6%), and 24 (12.1%) of HPV58 isolates, respectively. The sublineage A3 variants with T20I/G63S substitutions at E7 oncoprotein carried a significantly higher risk for high-grade cervical intraepithelial neoplasia (CIN2 or worse, CIN2+) when compared with other HPV58 variants (odds ratio = 4.41, P < 0.05). Nevertheless, there was no association between HPV58 (sub) lineages and cervical lesions. These data provide the critical characteristics of HPV58 variants to assist further investigation of carcinogenic association and the development of next generation vaccines and diagnostic assays in China.


Assuntos
Alphapapillomavirus , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/genética , Filogenia , Neoplasias do Colo do Útero/genética , Adolescente , Adulto , Idoso , Alphapapillomavirus/classificação , Alphapapillomavirus/genética , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia
12.
Infect Genet Evol ; 67: 210-221, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30458293

RESUMO

Members of the Alphapapillomavirus genus are causative agents for cervix cancer and benign lesions in humans. These viruses are classified according to sequence similarities in their L1 region. Yet, viral carcinogenicity has been associated with variations in the proteins encoded by the E6 and E7 genes. In order to relate evolutionary history with origin of carcinogenicity, we performed phylogenetic reconstructions using both nucleotide and predicted amino acid sequences of the L1, E6 and E7 genes. Whilst phylogenetic analysis of L1 reconstructed genus evolutionary history, phylogenies based on E6 and E7 proteins support the idea that mutations at amino acids S/Tx [V/L] (E6) and LxCxE (E7) might be responsible for carcinogenic potential. These findings indicate that virulence within Alphapapillomavirus have appeared multiple times during evolution. Our results reveal that oncogenic potential is not a monophyletic clade-specific adaptation but might be the result of positive selection on random mutations occurring on proteins involved in host infection during viral diversification.


Assuntos
Alphapapillomavirus/classificação , Alphapapillomavirus/genética , Transformação Celular Viral , Evolução Molecular , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus/genética , Filogenia , Tropismo Viral , Sequência de Aminoácidos , Sequência de Bases , Biologia Computacional/métodos , Sequência Conservada , Feminino , Genótipo , Humanos , Mutação , Proteínas Oncogênicas Virais/química , Proteínas E7 de Papillomavirus/química , Neoplasias do Colo do Útero/etiologia
13.
Expert Rev Mol Diagn ; 19(1): 63-70, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30575409

RESUMO

Introduction: The majority of squamous cell carcinoma (SCC) of the oropharynx, one of the sites within the head and neck region, is now associated with high-risk human papillomavirus (HPV) in North America. Several modalities are available to determine the HPV status, however, the understanding of each assay in its application and limitations is essential for accurate interpretation and appropriate utilization of results in management of these patients. Areas covered: This expert review will cover the role of HPV in head and neck squamous cell carcinoma (HNSCC), indications for HPV testing, HPV detection methods in tumors, saliva and serum, and exploiting HPV status as a prognostic biomarker of clinical outcome in HNSCC. Expert commentary: The HPV status is the most significant diagnostic and prognostic biomarker in HNSCC, specifically in the oropharynx. Research underway is currently delineating the role of HPV and p16 testing in non-oropharyngeal sites. While the feasibility of non-invasive serum and saliva testing for HPV detection has been established, the clinical application of these assays is still evolving.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Testes de DNA para Papilomavírus Humano/métodos , Alphapapillomavirus/genética , Alphapapillomavirus/patogenicidade , Carcinoma de Células Escamosas/virologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos
14.
Medicine (Baltimore) ; 97(45): e13206, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30407360

RESUMO

This study is to investigate the cervical human papillomavirus (HPV) infection rate in women of Urumqi, China.The epidemiological questionnaire survey was used to study 2300 women in Urumqi with a prospective research method. The second-generation hybrid capture assay, cervical liquid-based cytology test, colposcopy, and cervical biopsy were used to screen CC.In 2300 cases, HPV was detected in 385 cases with infection rate of 16.74%. The infection rates of Uygur and Han women were 20.08% and 13.39%, respectively, with significant differences (P <.05). Among all age groups, the infection rate was highest in the age group of 20 to 25 years (with infection rate of 22.22%), followed by the age group of 45 to 49 years (with infection rate of 18.78%). In 8 districts, the highest positive rate was in Saybagh District with infection rate of 24.79%, followed by Urumqi County with infection rate of 19.05%, and the lowest was in Toutunhe District with infection rate of 10.86%. There was no significant difference in HPV infection among all age groups or among 8 districts of Urumqi. HPV infection rates were 10.48%, 84.52%, 92.94%, 100% in chronic cervicitis, low grade and high-grade intraepithelial neoplasia and CC group, respectively. The difference was statistically significant (P <.05).The HPV infection rate of Uygur is higher than that in Han ethnic in Urumqi. The infection rate of HPV increases with the severity of cervical lesions.


Assuntos
Alphapapillomavirus/genética , Colo do Útero/virologia , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/virologia , Adulto , Colo do Útero/patologia , China/epidemiologia , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Adulto Jovem
15.
Biomed Res Int ; 2018: 2897937, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402468

RESUMO

Cervical cancer is one of the leading causes of cancer-related deaths among women and it is caused by the human papillomavirus (HPV). High variation has been reported in the attribution of specific HPV genotypes to cervical neoplasia among various geographic regions. For effective control of cervical cancer through HPV vaccination, it is essential to estimate the cost-effectiveness of vaccination, to monitor the potential transition into other HPV genotypes, and to understand the distribution of specific HPV genotypes across a specific geographic region. In this study, the distribution of HPV genotypes was investigated in southeast China, from 2011 to 2016. The 12,816 cervical swabs collected from women (age 18-78 years, median 43.6 years) outpatients were analyzed. HPV prevalence among 12,816 cervical swabs analyzed was 22.3% (2,856/12,816). Among these positive cases, 2,216 had only one HPV genotype while 640 had multiple HPV genotypes. The cases with multiple types revealed 23 different HPV genotypes with the five most prevalent being HPV18 (18.2%), HPV52 (14.1%), HPV16 (11.9%), HPV58 (10.6%), and HPV33 (5.5%). The rates of HPV infection in patients with cervical inflammation, CIN-1, CIN-2, CIN-3, squamous carcinoma, and adenocarcinoma were 38.4%, 80.5%, 82.6%, 92.3%, 97.5%, and 93.4%, respectively. Four HPV genotypes, HPV18, HPV16, HPV52, and HPV58, were more prevalent in patients with CIN-2-CIN-3 and invasive cervical cancer. A comparison of HPV genotypes attribution to cervical cancer between southeast China and global incidences revealed distinct differences. Due to this unique prevalence, it is essential to streamline the vaccination development protocol prior to administering vaccines based on global data.


Assuntos
Alphapapillomavirus/genética , Genótipo , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/genética , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Prevalência , Neoplasias do Colo do Útero/virologia
16.
F1000Res ; 7: 606, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30345020

RESUMO

Background: Toll-like receptor 9 (TLR9) plays a key role in the elimination of viral pathogens by recognising their CpG DNA. Polymorphisms in the TLR9 gene may influence their recognition and subsequent elimination. Therefore, the present study was designed to elucidate the role of a rare unexplored TLR9 gene polymorphism C296T/ Pro99Leu (rs5743844) in cervical cancer susceptibility among Indian women. Methods: The genotyping of TLR9 Pro99Leu polymorphism in 110 cervical cancer patients and 141 healthy controls was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The genotype frequency detected in both cervical cancer and control populations was 1.0 (CC), 0.0 (CT) and 0.0 (TT); while the allele frequency was found to be 1.0 (C) and 0.0 (T). Conclusions: The present study results demonstrate no involvement of TLR9 C296T/ Pro99Leu polymorphism in cervical cancer susceptibility and supports worldwide minor allele frequency (MAF) (0.0002) status of the same as no nucleotide variation was detected in any of the study participants.


Assuntos
Polimorfismo de Nucleotídeo Único , Receptor Toll-Like 9/genética , Neoplasias do Colo do Útero/genética , Adulto , Alphapapillomavirus/genética , Estudos de Casos e Controles , Feminino , Genes Virais , Humanos , Pessoa de Meia-Idade , Receptor Toll-Like 9/química , Neoplasias do Colo do Útero/virologia
17.
Int J Mol Sci ; 19(9)2018 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-30208597

RESUMO

In this diagnostic test validation study, we assessed the clinical accuracy and HPV genotyping performance of the INNO-LiPA HPV Genotyping Extra II (INNO-LiPA) within the VALGENT-3 framework. VALGENT is designed to assess the analytical and clinical performance of HPV tests with genotyping capacity. The VALGENT-3 panel comprised 1300 consecutive cervical cell specimens enriched with 300 samples with abnormal cytology obtained from women attending the Slovenian cervical cancer screening programme. The INNO-LiPA allows type-specific detection of 32 HPV types; however, for the clinical accuracy assessment, we considered it as high-risk (hr)HPV positive when at least one of the following HPV types was present: HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58, HPV59, and HPV68. Clinical accuracy for detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was compared between INNO-LiPA and Hybrid Capture 2 (HC2), which is a standard comparator test for HPV tests used in cervical cancer screening. In addition, hrHPV and type-specific detection HPV types were compared between INNO-LiPA and Linear Array HPV Genotyping Test (Linear Array). The prevalence of hrHPV determined by INNO-LiPA was 17.1% (95% CI, 15.0⁻19.2%) in the screening population. HrHPV testing with INNO-LiPA had a sensitivity for CIN2+ of 96.9% (95% CI, 92.1⁻99.1%) which was non-inferior to HC2 (relative sensitivity of 1.01; 95% CI, 0.97⁻1.04; pn.inf = 0.0002) and a specificity for ≤CIN1 of 85.3% (95% CI, 83.2⁻87.3%) which was inferior to HC2 (relative specificity of 0.95; 95% CI, 0.93⁻0.97; pn.inf = 0.9998). Genotyping agreement between INNO-LiPA and Linear Array was excellent for hrHPV, HPV16, HPV18, HPV35, HPV45, HPV58 and HPV59, but good or fair for other HPV types. To conclude, INNO-LiPA demonstrated non-inferior clinical sensitivity but lower specificity compared to HC2 in addition to excellent concordance compared to Linear Array for hrHPV and some genotypes.


Assuntos
Alphapapillomavirus/genética , Técnicas de Genotipagem/métodos , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Alphapapillomavirus/isolamento & purificação , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/virologia , DNA Viral/genética , Testes Diagnósticos de Rotina , Detecção Precoce de Câncer , Feminino , Humanos , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico
18.
Zhonghua Yu Fang Yi Xue Za Zhi ; 52(9): 946-950, 2018 Sep 06.
Artigo em Chinês | MEDLINE | ID: mdl-30196644

RESUMO

Objective: To investigate the infection status and genotype distribution of cervical human papillomavirus (HPV) in women of different ethnic groups and different ages in Yili, Xinjiang Uygur Autonomous Region (Xinjiang). Methods: By using the convenient sampling method, 54 760 women from November 2015 to May 2017 seeking for service in gynecological clinics in a general hospital in Yili, Xinjiang, were selected as the research subjects, and 3 445 samples of cervical mucous exfoliative cells were collected, and the social information of their ethnic and age was collected at the same time. The inclusion criteria were those with sexual life, cervical integrity, and ethnic groups for Han or Uygur or Kazak. PCR-reverse dot blot hybridization was used to detect HPV genotyping in exfoliated cells, and chi-square test was used to compare the difference of HPV positive rate among different ethnic groups. Then, according to ethnicity and age, the differences in positive rates of different ages and ethnic groups were compared in each layer. Results: The positive rate of HPV was 25.6% (882 cases), of which the Han, Uygur and Kazakh were 27.9% (564 cases), 22.9% (196 cases) and 21.6% (122 cases), and the difference was statistically significant (χ(2)=13.80, P=0.001). The most prevalent high-risk genotypes of Han women were HPV16/52/58, accounting for 24.8% (140 cases), 17.7% (100 cases) and 9.8% (55 cases), respectively. The most prevalent high-risk genotypes of Uygur women were HPV16/52/53, accounting for 34.2% (67 cases), 12.8% (25 cases), 9.2% (18 cases), respectively. The most prevalent high-risk genotypes of Kazak were HPV16/52/53, accounting for 37.7% (46 cases), 17.2% (21 cases), 12.3% (15 cases), respectively. The highest rate of HPV in Uygur patients aged ≥61 years was 41.5% (22 cases), and the lowest in group 36-40 years old, 15.9% (21 cases), the difference between different age groups was statistically significant (χ(2)=35.01, P<0.001). Conclusion: The positive rate of HPV infection among Han, Uygur and Kazak in Yili Prefecture of Xinjiang was different, and the HPV positive genotype differs among different ethnic groups.


Assuntos
Alphapapillomavirus/genética , Neoplasia Intraepitelial Cervical/etnologia , Neoplasia Intraepitelial Cervical/virologia , Grupos Étnicos/estatística & dados numéricos , Infecções por Papillomavirus/etnologia , Infecções por Papillomavirus/virologia , Adulto , Distribuição por Idade , China/epidemiologia , Feminino , Genótipo , Papillomavirus Humano 16/genética , Humanos , Pessoa de Meia-Idade
19.
PLoS One ; 13(8): e0201653, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30075010

RESUMO

Bivalent human papillomavirus (HPV) vaccine was incorporated into the childhood vaccination calendar in Galicia, Spain in 2008. The objectives of this study were to estimate direct, indirect and total effectiveness of HPV vaccine and to identify sexual habits changes in the post-vaccination period in Galicia, Spain.Endocervical scrapings of 745 women attending 7 Health Areas of the Galician Public Health Service were collected in the post-vaccination period, from 2014-2017. Two groups were studied: women born between 1989 and 1993 (n = 397) and women born in 1994 or later (n = 348). Twelve high-risk human papillomavirus (HR-HPV) genotypes were detected by Cobas® 4800 HPV test (Roche Diagnostics, Mannheim, Germany). The Linear Array® HPV Genotyping Test (Roche Diagnostics) was used for HR-HPV genotype detection other than HPV 16/18. Information about sexual habits was collected by a self-filled questionnaire. Post-vaccination data were compared to previously published pre-vaccination data obtained between 2008 and 2010 in Galicia from women of the same age (18-26 years old, n = 523). The Stata 14.2 software was employed for statistical analyses.Data from 392 unvaccinated and 353 vaccinated women were compared. For unvaccinated and vaccinated women, HPV 16/18 prevalence was 9.2% and 0.8%, respectively, and HPV 31/33/45 prevalence was 8.4% and 1.1%, respectively. Direct, indirect and total effectiveness of the HPV vaccine were (%, 95% CI): 94 (72-99), 30 (-11-56) and 95 (79-99), respectively, for HPV 16/18 and 83 (46-94), -10 (-88-33) and 84 (54-94), respectively, for HPV 31/33/45. The number of women with first intercourse before 17 years old and 3 or more sexual partners along life was higher in the post-vaccination period (p < 0.05). A positive impact of bivalent HPV vaccine was observed, both on direct and cross protection. Sexual habits could have changed in the post-vaccination period.


Assuntos
Alphapapillomavirus/classificação , Técnicas de Genotipagem/métodos , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/administração & dosagem , Avaliação de Programas e Projetos de Saúde/métodos , Adulto , Alphapapillomavirus/genética , Alphapapillomavirus/isolamento & purificação , Estudos de Casos e Controles , Feminino , Humanos , Vacinação em Massa , Infecções por Papillomavirus/prevenção & controle , Gravidez , Prevalência , Kit de Reagentes para Diagnóstico , Comportamento Sexual , Espanha , Inquéritos e Questionários , Adulto Jovem
20.
J Infect Dis ; 218(11): 1746-1752, 2018 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-30053247

RESUMO

Background: High-risk human papillomavirus (hrHPV)-induced anal low-grade squamous intraepithelial lesions (LSILs) have the potential to progress to high-grade squamous intraepithelial lesions (HSILs). We investigated whether anal hrHPV infections, particularly types 16 and 18, predict LSIL-to-HSIL progression. Methods: One hundred forty-six human immunodeficiency virus (HIV)-infected and 22 HIV-uninfected patients with anal LSILs underwent cytology, HPV genotyping (16, 18, and pooled 12 hrHPV types), and high-resolution anoscopy-guided biopsy at baseline and surveillance. The associations between the rate of LSIL-to-HSIL progression and HPV types as well as longitudinal HPV-16/18 status were assessed by fitting separate Cox regression models. Results: At baseline, 91% of patients harbored hrHPV: HPV-16/18 (44%) and non-16/18 (86%). Upon follow-up (median, 20 [range, 6-36] months), 41% developed HSIL (84% at the same anatomic location as the initial LSIL and 16% at a different location). Baseline HPV-16/18-positive patients had greater probability of progression than patients with non-16/18 types or negative (67%, 25%, and 7%, respectively; P < .001). Persistent HPV-16/18 conferred the highest probability of progression (70%), followed by intermittent HPV-16/18 positivity (52%). In unadjusted and adjusted analyses, baseline and persistent HPV-16/18 were significantly associated with LSIL-to-HSIL progression. Conclusions: Anal LSIL patients who are positive for hrHPV, especially HPV-16/18, have an increased risk of developing HSIL. Type-specific HPV testing could serve as a risk stratification tool, providing prognostic information.


Assuntos
Alphapapillomavirus/genética , Doenças do Ânus , Infecções por Papillomavirus , Lesões Intraepiteliais Escamosas Cervicais , Adulto , Idoso , Doenças do Ânus/epidemiologia , Doenças do Ânus/patologia , Doenças do Ânus/virologia , DNA Viral/análise , DNA Viral/genética , Progressão da Doença , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Lesões Intraepiteliais Escamosas Cervicais/epidemiologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Adulto Jovem
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