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1.
BMC Infect Dis ; 21(1): 400, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931022

RESUMO

BACKGROUND: Self-sampling for human papillomavirus (HPV) testing is a feasible option to improve the cervical screening coverage. However, an ideal triage method for HPV-positive self-samples does not yet exist. The aim of this study was to explore the utility of HPV genotyping and p16INK4a immunostaining (p16) in triaging HPV-positive self-samples, focusing on HPV-positive, cytology-negative (HPCN) women. METHODS: A total of 73,699 women were screened in a cervical screening project in China via SeqHPV assay on self-samples. HPV-positive women were called-back and collected cervical sample for p16 immunostaining and liquid-based cytology, those who met any result of HPV16/18+ or visual inspection with acetic acid (VIA) + or p16+ were referred for colposcopy, and HPCN women with adequate data on p16 and pathology were analyzed. A triage strategy was considered acceptable if the negative predictive value (NPV) for cervical intraepithelial neoplasia 3 or worse (CIN3+) was 98% or more, combined with an improvement of sensitivity and specificity for CIN2+/CIN3+ in reference to the comparator, being HPV16/18 + . RESULTS: A total of 2731 HPCN women aged 30-64 years were enrolled, 136 (5.0%) CIN2+ and 53 (1.9%) CIN3+ were detected. Five triage strategies met the criteria: p16+; HPV16/33+; 'HPV16+ or HPV33/58/31/35+&p16+'; 'HPV16/33+ or HPV58/31/35+&p16+'; HPV16/18/31/33/45/52/58 + & p16+. These strategies required less or similar colposcopy referrals, and less colposcopies to detected one case of CIN2+/CIN3+, achieving favorable false positive (negative) rates to the comparator. Among them, p16 staining detected 83.1% (79.2%) of underlying CIN2 + (CIN3+) in HPCN women. Moreover, three triage strategies were favorable in sensitivity and/or specificity to the 'HPV16/33+' strategy: p16+; 'HPV16+ or HPV33/58/31/35 + &p16+'; HPV16/18/31/33/45/52/58 + &p16 + . CONCLUSIONS: Genotyping for HPV16/33 could be utilized to optimize the management of HPCN women. Moreover, p16 immunostaining, either alone or combined with extended genotypes, is more effective than HPV genotypes alone in the triage of HPCN women.


Assuntos
Alphapapillomavirus/genética , Neoplasia Intraepitelial Cervical/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/patologia , Adulto , Neoplasia Intraepitelial Cervical/virologia , China , Colposcopia , Citodiagnóstico , Detecção Precoce de Câncer/métodos , Feminino , Genótipo , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos
2.
BMC Cancer ; 21(1): 281, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726684

RESUMO

BACKGROUND: Cervical cancer is the fourth cancer worldwide. The Human Papilloma Virus is responsible for 99% of the cases but the distribution of its genotypes varies among populations. We aimed to identify HPV genotypes distribution in women with grade 2/3 cervical intraepithelial dysplasia or invasive cervical cancer in Guadeloupe, a French Caribbean territory with a population mainly of African descent. METHODS: We used paraffin-embedded tumors for viral DNA extraction from women diagnosed between 2014 and 2016 and identified by the population-based cancer registry. The HPV Genotyping was performed with the InnoLIPA HPV Genotyping Extra kit®. RESULTS: Overall, 213 samples out of the 321 eligible records were analyzed. The HPV status was positive for 94% of the cases. The five most common oncogenic HPV genotypes were HPV31 (47%), HPV33 (38%), HPV16 (32%), HPV44 (31%) and HPV26 (28%). HPV18 was found in only in 5% of the cases. Among the studied cases, 94% had multiple infections. More than 60% of single infections were HPV16-related, accounting for 35% of HPV16 infections. CONCLUSIONS: These results show a different distribution of oncogenic HPVs in Guadeloupe with "31 >  33 > 16" and a high frequency of multiple infections. Despite a lower coverage, the nine-valent vaccine is nevertheless adequate.


Assuntos
Neoplasia Intraepitelial Cervical/virologia , Coinfecção/epidemiologia , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/virologia , Adulto , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Colo do Útero/patologia , Colo do Útero/virologia , Coinfecção/diagnóstico , Coinfecção/prevenção & controle , Coinfecção/virologia , DNA Viral/isolamento & purificação , Feminino , Guadalupe/epidemiologia , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/isolamento & purificação , Humanos , Incidência , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/prevenção & controle
4.
Acta Obstet Gynecol Scand ; 100(3): 394-402, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33566361

RESUMO

INTRODUCTION: Human papillomavirus (HPV) testing as the primary cervical cancer screening method is implemented in several countries. We report data from the first round of a large Danish pilot implementation of HPV-based screening. Our aim was to compare colposcopy referrals, detection of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer, and positive predictive value (PPV) of colposcopy referral in HPV vs cytology-based screening. MATERIAL AND METHODS: From May 2017 to October 2018, women aged 30-59 years attending cervical cancer screening in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark were screened by primary HPV testing (n = 16 067) or primary cytology (n = 23 981) depending on municipality of residence. In the HPV group, women with HPV16/18, or other high-risk HPV types and abnormal cytology, were referred to immediate colposcopy. Women with other high-risk HPV types and normal cytology were invited for repeat screening with HPV test and cytology after 12 months. From a nationwide pathology register, we obtained information on screening results and subsequent histological diagnoses during up to 2.9 years after the first screen. PPVs included diagnoses within 1 year after referral. RESULTS: In the HPV group, 3.7% were referred to immediate colposcopy and 2.8% were referred at the 12-month repeat screening. The total referral to colposcopy was higher in the HPV (6.6%) than cytology group (2.1%) (age-adjusted relative referral = 3.05, 95% confidence interval [CI] 2.75-3.38). The detection of CIN3+ was higher in the HPV (1.5%) than the cytology group (0.8%) (age-adjusted relative detection = 1.88, 95% CI 1.56-2.28). The probability of CIN3+ among women referred to colposcopy (= PPV) was lower in the HPV (21.1%; 95% CI 18.7%-23.7%) than the cytology group (34.6%; 95% CI 30.7%-38.9%). In the HPV group, the PPV was lower among women referred at repeat screening (12.1%) than among women referred immediately (27.8%). CONCLUSIONS: Compared with cytology-based screening, HPV-based screening provided a 90% increased CIN3+ detection at the cost of a threefold increase in colposcopy referrals, when considering complete data from the prevalence round. Our findings support implementation of HPV-based screening in Denmark, but modifications of screening algorithms may be warranted to decrease unnecessary colposcopy referrals.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Técnicas Citológicas , Programas de Rastreamento/métodos , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Neoplasia Intraepitelial Cervical/virologia , Colposcopia , Dinamarca , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Encaminhamento e Consulta , Sistema de Registros , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
5.
BMC Cancer ; 21(1): 39, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413211

RESUMO

BACKGROUND: To improve the efficiency of early diagnosis systems for cervical cancer, the use of cellular and viral markers for identifying precancerous lesions with a greater probability to progress to cancer has been proposed. Several cellular proteins and markers of oxidative DNA damage have been suggested as possible biomarkers of cervical carcinogenesis; however, they have not been evaluated together. In this study, we analyzed the expression of the cellular markers p16INK4a, Ki-67, CyclinE1, TOP2A/MCM2, and telomerase, as well as the DNA oxidative damage markers ROS and 8-OHdG. The analyses were performed in liquid-based cervical cytology samples or biopsies with premalignant lesions or cervical cancer diagnosis, with the purpose of selecting a panel of biomarkers that allow the identification of precursor lesions with greater risk of progression to cervical cancer. METHODS: We analyzed 1485 liquid-based cytology samples, including 239 non-squamous intraepithelial lesions (NSIL), 901 low-grade squamous intraepithelial lesions (LSIL), 54 high-grade squamous intraepithelial lesions (HSIL), and 291 cervical cancers (CC). The biomarkers were analyzed by immunocytochemistry and Human Papilloma Virus (HPV) genotyping with the INNO-LiPA genotyping Extra kit. RESULTS: We found that all tested cellular biomarkers were overexpressed in samples with high risk-HPV infection, and the expression levels increased with the severity of the lesion. TOP2A/MCM2 was the best biomarker for discriminating between LSIL and HSIL, followed by p16INK4a and cyclinE1. Statistical analysis showed that TOP2A/MCM2 provided the largest explanation of HSIL and CC cases (93.8%), followed by p16INK4a (91%), cyclin E1 (91%), Ki-67 (89.3%), and telomerase (88.9%). CONCLUSIONS: We propose that the detection of TOP2A/MCM2, p16INK4a and cyclin E1 expression levels is useful as a panel of biomarkers that allow identification of cervical lesions with a higher risk for progression to CC with high sensitivity and precision; this can be done inexpensively, in a single and non-invasive liquid-based cytology sample.


Assuntos
Ciclina E/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Biópsia Líquida/métodos , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Proteínas Oncogênicas/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Lesões Pré-Cancerosas/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/cirurgia , Neoplasia Intraepitelial Cervical/virologia , Citodiagnóstico/métodos , Progressão da Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/cirurgia , Lesões Pré-Cancerosas/virologia , Prognóstico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/virologia
6.
Acta Obstet Gynecol Scand ; 100(4): 786-793, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33497480

RESUMO

INTRODUCTION: Visual inspection of the cervix with acetic acid is used to control the burden of cervical cancer in low- and middle-income countries. This method has some limitations and HPV DNA testing may be an alternative, but it is expensive and requires a laboratory setup. Cheaper and faster HPV tests have been developed. This study describe the agreement between a fast HPV test (careHPV) and hybrid capture 2 (HC2) in detection of high-risk HPV among Tanzanian women. MATERIAL AND METHODS: The study involved women attending routine cervical cancer screening at the Ocean Road Cancer Institute and Kilimanjaro Christian Medical Centre in Tanzania. The women were offered HIV testing. Two cervical samples were subsequently obtained; the first sample was processed at the clinics using careHPV and the second sample was transported to Denmark and Germany for cytology and HC2 analysis. Kappa statistic was calculated to assess the agreement between careHPV and HC2. The sensitivity, specificity and predictive values of careHPV were calculated using HC2 as reference. The analyses were done for the overall study population and stratified by testing site and HIV status. RESULTS: A total of 4080 women were enrolled, with 437 being excluded due to invalid information, lack of careHPV or HC2 results. Overall agreement between the tests was substantial with a kappa value of 0.69 (95% confidence interval [CI] 0.66-0.72). The sensitivity and specificity of careHPV was 90.7% (95% CI 89.6-91.8) and 84.2% (95% CI 81.2-86.8), respectively. The agreement was similar in the stratified analyses where the kappa values were 0.75 (95% CI 0.70-0.79) in women aged 25-34, 0.66 (95% CI 0.62-0.70) in women aged 35-60, 0.73 (95% CI 0.70-0.77) at the Ocean Road Cancer Institute, 0.64 (95% CI 0.60-0.69) at the Kilimanjaro Christian Medical Center, 0.73 (95% CI 0.68-0.79) in HIV-positive and 0.66 (95% CI 0.63-0.70) in HIV-negative women. The kappa value of 0.64 (95% CI 0.39-0.88) for cervical high-grade lesions indicates a substantial agreement between careHPV and HC2 in detecting HPV among women with cervical high-grade lesions. CONCLUSIONS: A substantial agreement was found between careHPV and HC2 in detecting HPV overall as well as detecting HPV among women with cervical high-grade lesions. However, given the limited resources available in low and middle-income countries, the HPV testing assay should be weighed against the cost-effectiveness of the test.


Assuntos
Testes de DNA para Papilomavírus Humano , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/virologia , Adulto , Biomarcadores Tumorais/isolamento & purificação , Neoplasia Intraepitelial Cervical/virologia , DNA Viral/isolamento & purificação , Detecção Precoce de Câncer/métodos , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Tanzânia/epidemiologia
7.
Arch Virol ; 166(3): 853-862, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33486629

RESUMO

The aim of this study was to describe the distribution of human papillomavirus (HPV) genotypes among cervical cancers and pre-cancers in Shaanxi province of western China. A total of 17,341 women who were screened for cervical cancer from January 2014 to December 2016, using HPV genotyping and ThinPrep cytologic test were included. The prevalence and attribution of HPV genotypes were stratified by cervical lesion and age group. Of the subjects, 26.3% were infected with HPV, 28.0% of whom had multiple infections. The crude HPV prevalence increased from atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions (ASCUS/LSIL, 64.3%) to high-grade squamous intraepithelial lesions (HSIL, 79.8%) and to invasive cervical cancer (ICC, 89.7%, P < 0.001). The three most prevalent genotypes were HPV 16 (8.0%), 58 (4.2%), and 52 (4.0%), and HPV 16, 31 and 33 were positively correlated with increased severity of cervical lesions. Additionally, the divalent vaccine genotypes HPV 16 and 18 accounted for 68.2% of ICC cases. Although 78.5% of ICC and 60.3% of HSIL cases were attributed to 9-valent vaccine genotypes, the other genotypes not covered by any vaccine still resulted in increases in coverage, with 1.5% for ICC, 5.3% for HSIL, and 13.5% for ASCUS/LSIL. HPV prevalence in western China was consistent with other regions of China. Early vaccination with 9-valent HPV vaccine is recommended in this locality for females younger than 26 years with no prior infection, while divalent the vaccine is more appropriate for women between 26 and 45 years, considering the efficacy, safety and cost-effectiveness of vaccines.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Papillomavirus Humano 31/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Neoplasia Intraepitelial Cervical/virologia , China/epidemiologia , Feminino , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Papillomavirus Humano 31/genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/uso terapêutico , Prevalência , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação
8.
Zhonghua Fu Chan Ke Za Zhi ; 55(11): 784-790, 2020 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-33228350

RESUMO

Objective: To evaluate the value of p16INK4a detected by p16INK4a immunostaining as a new generation of cervical cytology for primary screening and secondary screening in population-based cervical cancer screening, and in improving cytological diagnosis. Methods: Between 2016 and 2018, 5 747 non-pregnant women aged 25-65 years with sexual history were recruited and underwent cervical cancer screening via high-risk (HR)-HPV/liquid-based cytological test (LCT) test in Shenzhen and surrounding areas. All slides were immuno-stained using p16INK4a technology, among them, 902 cases were offered p16INK4a detection during primary screening, and the remaining 4 845 cases were called-back by the virtue of abnormal HR-HPV and LCT results for p16INK4a staining. Participants with complete LCT examination, HR-HPV test, p16INK4a staining and histopathological examination results were included in this study. The performance of p16INK4a in primary and secondary screening, and in assisting cytology to detect high grade squamous intraepithelial lesion [HSIL, including cervical intraepithelial neoplasia (CIN) Ⅱ or Ⅲ] or worse [HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+] were analyzed. Results: (1) One-thousand and ninety-seven cases with complete data of p16INK4a and histology were included. Pathological diagnosis: 995 cases of normal cervix, 37 cases of low grade squamous intraepithelial lesion (LSIL), 64 cases of HSIL and one case of cervical cancer were found. Among them, 65 cases of HSIL (CIN Ⅱ)+ and 34 cases of HSIL (CIN Ⅲ)+ were detected. The positive rate of p16INK4a in HSIL (CIN Ⅱ)+ was higher than that in CINⅠ or normal pathology (89.2% vs 10.2%; P<0.01). (2) p16INK4a as primary screening for HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+ was equally sensitive to primary HR-HPV screening (89.2% vs 95.4%, 94.1% vs 94.1%; P>0.05), but more specific than HR-HPV screening (89.8% vs 82.5%, 87.7% vs 80.2%; P<0.05). p16INK4a was equally sensitive and similarly specific to cytology (≥LSIL; P>0.05). (3) The specificity of LCT adjunctive p16INK4a for detecting HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+ were higher than that of LCT alone or adjunctive HR-HPV (P<0.01), while the sensitivity were similar (P>0.05). (4) p16INK4a staining as secondary screening: p16INK4a was significantly more specific (94.1% vs 89.7%, 91.9% vs 87.4%; P<0.01) and comparably sensitive (84.6% vs 90.8%, 88.2% vs 91.2%; P>0.05) to cytology for triaging primary HR-HPV screening. HPV 16/18 to colposcopy and triage other HR-HPV with p16INK4a was equally sensitive (88.2% vs 94.1%; P=0.500) and more specific (88.3% vs 83.0%; P<0.01) than HPV 16/18 to colposcopy and triage other HR-HPV with LCT≥ atypical squamous cells of undetermined significance (ASCUS), and the referral rate decreased (14.0% vs 19.4%; P=0.005). Conclusions: For primary screening, p16INK4a is equally specific to cytology and equally sensitive to HR-HPV screening. p16INK4a alone could be an efficient triage after primary HR-HPV screening. In addition, p16INK4a immunostaining could be used as an ancillary tool to cervical cytological diagnosis, and improves its accuracy in cervical cancer screening.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , Detecção Precoce de Câncer/métodos , Imuno-Histoquímica/métodos , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/análise , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/virologia , Inibidor p16 de Quinase Dependente de Ciclina/fisiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Gravidez , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
9.
BMC Infect Dis ; 20(1): 808, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153446

RESUMO

BACKGROUND: Although more than 10 years have passed since HPV vaccination was implemented, first as an interim programme (Emergent vaccine promotion programme) in November 2010, followed by incorporating into the National Immunization Programme in April, 2013 and suspended in June 2013, limited studies have investigated the HPV vaccine effectiveness against high-grade cervical lesions in Japan. METHODS: We collected the matched data of the results of cervical biopsy and history of vaccination from the Japan Cancer Society database. The subjects were women aged 20 to 29 years screened for cervical cancer between April, 2015 and March, 2017, and with information on HPV vaccination status. We estimated the relative risk of developing high-grade cervical lesions in vaccinated subjects using Poisson regression as compared to unvaccinated subjects. RESULTS: Among the 34,281 women screened, 3770 (11.0%) were vaccinated. The prevalence of CIN2+ was statistically significantly lower in the vaccinated women as compared to the unvaccinated women (Vaccine Effectiveness (VE) =76%; RR = 0.24, 95% CI:0.10-0.60). High VE against CIN3+ was also observed (91%; RR = 0.09, 95% CI:0.00-0.42). CONCLUSION: Women aged 20-29 years who received at least one dose of HPV vaccine had a significantly lower risk of high-grade cervical lesions than those not vaccinated. In Japan, HPV vaccination should be resumed in order to reduce the incidence of cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Vacinação , Adulto , Neoplasia Intraepitelial Cervical/classificação , Neoplasia Intraepitelial Cervical/virologia , Estudos Transversais , Feminino , Humanos , Programas de Imunização , Incidência , Japão/epidemiologia , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/administração & dosagem , Prevalência , Resultado do Tratamento , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/virologia , Adulto Jovem
10.
Medicine (Baltimore) ; 99(46): e23155, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181688

RESUMO

BACKGROUND: There are currently no available standard drugs treating human papillomavirus (HPV) infection, especially for patients with low-grade cervical lesion. Several therapies are explored but the results are inconclusive. The objective of this study was to evaluate the efficacy of reported non-invasive treatments in patients with HPV infection and cervical lesions by meta-analysis. METHODS: A comprehensive search of prospective and randomized studies published from April 2000 to April 2020 was conducted in electronic databases. The statistical analyses of the pooled risk ratios (RRs) and the corresponding 95% confidence intervals (95% CIs) were performed using the Revman 5.2 software. RESULTS: Twelve articles including 12 randomized controlled studies and 1 prospective controlled randomized pilot study were enrolled. Therapeutic medications included biological and herbal regimen, interferon regimen and probiotics. The meta-analysis showed the experimental treatments had a statistically significant improvement in HPV clearance rate compared with the controls (RR = 0.71, 95% CI [0.63, 0.80], P < .00001); subgroup analyses stratified by regimen categories were consistent with results in the overall group. Treatment using biological and herbal regimen, interferon regimen or probiotics also resulted in a beneficial outcome in regression rate of cervical lesions compared with the controls (RR = 0.55, 95% CI [0.39, 0.79], P = .001). The trend was more favorable in the probiotics than that in the biological and herbal regimen (RR 0.48 vs 0.72). CONCLUSION: Treatment of biological and herbal regimen, interferon regimen and probiotics benefit patients who have HPV infection and cervical lesions. Both the clearance of HPV and regression of cervical lesions are significant. More studies with less heterogeneity are needed to draw a concrete conclusion.


Assuntos
Produtos Biológicos/farmacologia , Neoplasia Intraepitelial Cervical/terapia , Interferons/farmacologia , Infecções por Papillomavirus/terapia , Preparações de Plantas/farmacologia , Antivirais/farmacologia , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Infecções por Papillomavirus/complicações , Resultado do Tratamento
11.
Zhonghua Fu Chan Ke Za Zhi ; 55(10): 708-715, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33120484

RESUMO

Objective: Evaluation of the clinical value of the BioPerfectus multiplex real time (BMRT)-HPV for cervical cancer screening. Methods: Physician-collected specimens of 1 495 women who were positive of Cobas 4800 HPV (Cobas-HPV), HPV genotyping based on SEQ uencing (SEQ-HPV), and (or) cytology ≥low grade squamous intraepithelial lesion (LSIL) in the primary screening of Chinese Multiple-center Screening Trial (CHIMUST), and 2 990 women selected from those who were negative of primary screening in the same project through nested control randomization with age-matching were tested for BMRT-HPV, which reported type-specific viral loads/10 000 cells in each specimen. With comparing to Cobas-HPV results and taking cervical histopathological diagnosis as the endpoint, the concordance of high-risk (HR)-HPV subtypes among the three assays was explored ,and the sensitivity and specificity of BMRT-HPV for cervical cancer screening were evaluated. Results: (1) The overall agreenment of HR-HPV subtypes between BMRT-HPV and Cobas-HPV, or SEQ-HPV test sample was 94.8%, 94.4%, with Kappa values 0.827, 0.814. (2) The sensitivity and specificity for cervical intraepithelial neoplasia (CIN) Ⅱ+ of BMRT-HPV, Cobas-HPV and SEQ-HPV were 92.62%, 94.26%, 93.44% and 84.67%, 83.25%, 82.76%, respectively. There were no significant difference in sensitivity among the three HPV assays (all P>0.05), but the specificity of BMRT-HPV for CIN Ⅱ+ was higher than those of Cobas-HPV and SEQ-HPV (P<0.01). The sensitivity for CIN Ⅲ+ of three HPV assays were all 100.00%, and the specificity for CIN Ⅲ+ of BMRT-HPV was higher than those of Cobas-HPV and SEQ-HPV (83.40% vs 81.95%, 83.40% vs 81.50%; P<0.01). The number of pathological examinations of colposcopy for cervical biopsy detected in 1 case of CIN Ⅱ+ or CIN Ⅲ+ in BMRT-HPV was less than those in Cobas-HPV and SEQ-HPV (P<0.01). When using HPV 16/18 + cytology ≥atypical squamous cell of undetermined signification (ASCUS) to triage HPV positive women among three assays, there was no different in the sensitivities of detecting CIN Ⅱ+ and CIN Ⅲ+ (P>0.05). The specificity BMRT-HPV was slightly higher than those in Cobas-HPV or SEQ-HPV (all P<0.05), and the colposcopy referral rate was lower than those in Cobas-HPV and SEQ-HPV (all P<0.05). Conclusions: BMRT-HPV is as sensitive as Cobas-HPV or SEQ-HPV for primary cervical cancer screening, and has higher specificity. Therefore it could be used as a primary screening method for cervical cancer, which is worthy of clinical application.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasia Intraepitelial Cervical/virologia , DNA Viral/análise , DNA Viral/genética , Detecção Precoce de Câncer , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Programas de Rastreamento/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Gravidez , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos
12.
BMC Infect Dis ; 20(1): 801, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121447

RESUMO

BACKGROUND: According to the 2006 American Society for Colposcopy and Cervical Pathology guidelines, positive CIN2 p16 in women over the age of 25 should be managed with excisional treatment. However, excisional treatment is associated with physical, psychological and obstetric morbidity and can have a negative impact on sexual function. In our study we sought to identify a clear management strategy, addressing the impact of routine use of p16 immunohistochemistry in this population and identify appropriate criteria for patient selection with the aim of reducing over-treatment. METHOD: We studied the medical records of 130 patients who had undergone laser therapy for CIN2. Each patient underwent colposcopy, biopsy and HPV test and were tested for p16 protein,. Patients were divided based on HPV infection into: single infections, multiple infections. All patients underwent ZTA laser therapy with follow-up (2-year follow-up). STATISTICAL ANALYSIS: Contingency tables were created to evaluate the correlation between single, multiple and CIN2+ infections. Values with p < 0.05 were considered statistically significant. RESULTS: Single infections had a histological regression of 61.8% (21/34) and a histological persistence rate of 35.3% (12/34), which was greater than the multiple infection rate. The common characteristic that the women with persistence and progression had was the dimension of the lesion and the genotype 16. Ten cases of histological persistence and the only case of progression had one lesion greater than three quarters of the cervix. CONCLUSIONS: With the progress of our understanding of the natural history of infection from human papillomavirus and the increasing use of colposcopy, thanks to the addition of HPV genotyping and the technique of immunohistochemistry, conservative management of these lesions is now possible.


Assuntos
Neoplasia Intraepitelial Cervical/complicações , Neoplasia Intraepitelial Cervical/terapia , Tratamento Conservador/métodos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/terapia , Adulto , Neoplasia Intraepitelial Cervical/virologia , Colposcopia , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , Progressão da Doença , Feminino , Seguimentos , Genótipo , Humanos , Imuno-Histoquímica , Terapia a Laser , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/virologia
13.
BMC Infect Dis ; 20(1): 642, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873233

RESUMO

BACKGROUND: Evidence suggested that vaginal microbiome played a functional role in the progression of cervical lesions in female infected by HPV. This study aimed at evaluating the influence of common vaginal infection on the carcinogenicity of high risk HPV (hr-HPV). METHODS: From January 15, 2017 to December 31, 2017, 310,545 female aged at least 30 years old had been recruited for cervical cancer screening from 9 clinical research centers in Central China. All the recruited participants received hr-HPV genotyping for cervical cancer screening and vaginal microenvironment test by a high vaginal swab. Colposcopy-directed biopsy was recommended for female who were infected with HPV 16 and HPV 18, and other positive hr-HPV types through test had undertaken triage using liquid-based cytology, cases with the results ≥ ASCUS among them were referred to colposcopy directly, and cervical tissues were taken for pathology examination to make clear the presence or absence of other cervical lesions. RESULTS: Among 310,545 female, 6067 (1.95%) were tested with positive HPV 16 and HPV 18, 18,297 (5.89%) were tested with other positive hr-HPV genotypes, cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3 and invasive cervical cancer (ICC) were detected in 861 cases, 377 cases, 423 cases, and 77 cases, respectively. Candida albicans and Gardnerella were not associated with the detection of cervical lesions. Positive trichomonas vaginitis (TV) was correlated with hr-HPV infection (p < 0.0001). Co-infection with TV increased the risk of CIN 1 among female infected with hr-HPV (OR 1.18, 95% CI: 1.42-2.31). Co-infection with TV increased the risk of CIN 2-3 among female infected with HPV 16 (OR 1.71, 95% CI: 1.16-2.53). CONCLUSIONS: Co-infection of TV and HPV 16 is a significant factor for the detection of cervical lesions.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Coinfecção/complicações , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Infecções por Papillomavirus/complicações , Vaginite por Trichomonas/complicações , Trichomonas vaginalis/isolamento & purificação , Neoplasias do Colo do Útero/epidemiologia , Adulto , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/virologia , China/epidemiologia , Coinfecção/diagnóstico , Colposcopia , Estudos Transversais , Citodiagnóstico , Detecção Precoce de Câncer/métodos , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Vaginite por Trichomonas/diagnóstico , Vaginite por Trichomonas/parasitologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia
14.
Arch Virol ; 165(11): 2633-2640, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32812092

RESUMO

Our aim was to analyze the prevalence of high-risk human papillomavirus (HR-HPV) and its association with risk factors related to cervical lesions. We used 362 cervical samples from a transversal study to detect nineteen types from the high-risk HPV clade by highly sensitive PCR. Unexpectedly, we found a very high prevalence of HPV type 66 (32.8%), particularly in low-grade squamous intraepithelial lesions. A significant association of HPV66 with previously sexually transmitted disease was observed (p < 0.05). Our results strongly suggest that HPV66 might be indicative of cervical lesions that will not progress to cancer. HPV genotyping by methods that grouped type 66 with other HR-HPV clade types should be interpreted with caution.


Assuntos
Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasia Intraepitelial Cervical/patologia , Detecção Precoce de Câncer , Feminino , Genótipo , Técnicas de Genotipagem , Humanos , Modelos Logísticos , México/epidemiologia , Pessoa de Meia-Idade , Papillomaviridae/classificação , Fatores de Risco , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem
15.
BMC Infect Dis ; 20(1): 629, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32842982

RESUMO

BACKGROUND: In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts. METHODS: The vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n = 78), women with low-grade squamous intraepithelial lesions (LSIL, n = 51), women with high-grade squamous intraepithelial lesions (HSIL, n = 23), women with invasive cervical cancer (Cancer, n = 9) and healthy women without HPV infection (Normal, n = 68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3-4) using Illumina MiSeq. RESULTS: HPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus, Gardnerella and Atopobium. Accordingly, HPV infection increased the relative abundance of Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus. The increased proportions of Bacillus, Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera. The most abundant bacterium in the LSIL group was Prevotella amnii. However, Prevotella timonensis, Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus, Sneathia, Acidovorax, Oceanobacillus profundus, Fusobacterium, Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis. Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs. CONCLUSIONS: This work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.


Assuntos
Biodiversidade , Neoplasia Intraepitelial Cervical/epidemiologia , Progressão da Doença , Microbiota/genética , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Vagina/microbiologia , Adulto , Idoso , Neoplasia Intraepitelial Cervical/virologia , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Lactobacillus/genética , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , RNA Ribossômico 16S/genética , Neoplasias do Colo do Útero/virologia
16.
Ann Epidemiol ; 49: 36-41, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32711054

RESUMO

PURPOSE: This study aimed to assess the association between body mass index and incident or persistent cervical high-risk human papillomavirus (hrHPV) infection. METHODS: This cohort study included 6809 women from the general Danish population who participated in two clinical visits (in 1991-1993 and in 1993-1995). Height and weight were measured by nurses, lifestyle data were obtained by structured interviews, and cervical cytology samples were obtained for hrHPV DNA testing. We conducted log-binomial regression to estimate risk ratios (RRs) with 95% confidence intervals (CIs) of incident and type-specific persistent hrHPV infection according to body mass index, adjusting for age, education, smoking, and the number of sexual partners in the past year. RESULTS: We found no increased risk of incident hrHPV infection in women who were underweight (RRadjusted, 0.97; 95% CI, 0.64-1.48), overweight (RRadjusted, 0.98, 95% CI, 0.82-1.17), or obese (RRadjusted, 0.93; 95% CI, 0.63-1.36) compared with women of normal weight. The risk of hrHPV persistence was similar in overweight (RRadjusted, 0.98; 95% CI, 0.71-1.34) and obese (RRadjusted, 1.00; 95% CI, 0.56-1.79) women compared with women of normal weight, whereas underweight women had a lower risk (RRadjusted, 0.32; 95% CI, 0.11-0.95). CONCLUSIONS: Overweight and obesity were not associated with HPV incidence or persistence when adjusting for sexual behavior.


Assuntos
Índice de Massa Corporal , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/epidemiologia , Colo do Útero/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Neoplasia Intraepitelial Cervical/virologia , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Programas de Rastreamento , Obesidade/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Vigilância da População , Magreza/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia
17.
Medicine (Baltimore) ; 99(27): e21005, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629719

RESUMO

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


Assuntos
Neoplasia Intraepitelial Cervical/terapia , Hipertermia Induzida/métodos , Neoplasias do Colo do Útero/terapia , Adulto , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/virologia
18.
Acta Cytol ; 64(5): 442-451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32599588

RESUMO

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


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasia Intraepitelial Cervical/patologia , Interleucina-23/metabolismo , Interleucina-2/metabolismo , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/patologia , Adulto , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/virologia , Estudos Transversais , Regulação para Baixo , Feminino , Humanos , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia
19.
Int J Gynecol Cancer ; 30(8): 1097-1100, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32487685
20.
PLoS One ; 15(5): e0232107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379782

RESUMO

OBJECTIVE: To explore the relationship between the viral load reflected by the Ct value of Cobas 4800 HPV test and cervical lesions, and the effectiveness of the viral load for secondary triage of HPV-positive women. METHODS: The Chinese Multi-Center Screening Trial (CHIMUST) evaluated both self-collected samples and physician-collected samples from women, aged 30 to 59, who were screened for cervical cancer in 6 regions across China. Using physician collected samples, the relationship between the HPV-Ct values of different subtypes and the cervical lesions was analyzed. Then the combined use of the HPV-Ct values with the HPV subtypes was evaluated as a secondary screening algorithm for the women who were HPV positive. RESULTS: The Ct values of HPV16 and 12 other HPV subtypes(12-type pool), tested with Cobas decreased with the progression of cervical lesion (HPV16: r = -0.429, P<0.001; 12 other HR-HPV subtypes: r = -0.099, P<0.01). The HPV18-Ct value was not correlated with cervical lesion(P>0.05). Compared with HPV16/18 and cytology (HPV16/18 positive and 12-type pool plus cytology ≥ ASC-US), the sequential secondary screening using HPV16/18 and the viral load of 12-type pool (cut-point HPV-Ct≤31) had equal sensitivities for CIN2+ and CIN3+ (83.1%vs.80.3%,100%vs.92.6%,P>0.05), with slightly lower specificities (96.2%vs.94.4%,96.5%vs.93.9%,P<0.001) and higher colposcopy referral rate (4.90%vs.6.59%, P<0.05), but required no cytology. CONCLUSION: Type-specific HPV viral load is closely related to cervical lesions severity. It is feasible and efficient to use HPV16/18 and the viral load of 12 other HPV subtypes (with cut-point HPV-Ct≤31) as the secondary screening for HPV positive women. This algorithm may be useful in low resource regions.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias do Colo do Útero/diagnóstico , Carga Viral/métodos , Adulto , Grupo com Ancestrais do Continente Asiático , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/patologia , China/epidemiologia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/virologia , Sensibilidade e Especificidade , Sorogrupo , Manejo de Espécimes/métodos , Triagem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
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