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1.
BMC Cancer ; 21(1): 997, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34488676

RESUMO

BACKGROUND: miR-21, miR-26b, miR-221/222 and miR-126 play crucial roles in cervical cancer development. Studies have shown that polymorphisms in miRNA genes can affect miRNA expression, which might be associated with cancer development. METHODS: Ten single-nucleotide polymorphisms (SNPs) in the miR-21, miR-26b, miR-221/222 and miR-126 genes (rs1292037, rs13137 in miR-21; rs2227255, rs2227258 in miR-26b; rs2858061, rs34678647, rs2858060, rs2745709 in miR-221/222; rs2297537, rs2297538 in miR-126) were selected, and genotyped in a total of 2176 individuals, including 435 patients with cervical intraepithelial neoplasia (CIN), 743 patients with cervical cancer (CC) and 998 healthy persons using TaqMan assays, and their associations with CIN and CC were evaluated. RESULTS: Our results showed significant differences for the rs2297538 genotypes between the CIN and CC groups (P = 0.001). In addition, our results also showed significant differences for the rs2297537 alleles between the CIN and CC groups (P = 0.003), and the C allele of rs2297537 might be associated with a decreased risk of CC (OR = 0.72, 95%CI: 0.58-0.90). At the inheritance analysis, between the CIN and control groups, the T/T-T/C genotype in rs1292037 and A/A-A/T genotype in rs13137 might be associated with an increased risk of CIN in the recessive model (OR = 1.61, 95% CI: 1.17-2.20 and OR = 1.58, 95% CI: 1.15-2.15). In addition, the C/C-T/T genotype of rs2745709 might be associated with a decreased risk of CIN in the overdominant model (OR = 0.66, 95% CI: 0.52-0.82). Between, CIN and CC group, the T/T-C/C genotype in rs1292037 and A/A-T/T genotype in rs13137 might be associated with an increased risk of CC in the overdominant model (OR = 1.43, 95% CI: 1.12-1.81 and OR = 1.42, 95% CI: 1.12-1.80). The rs2297538 G/G-A/G genotype might be associated with an increased risk of CC in the recessive model (OR = 2.83, 95% CI: 1.52-5.25). The rs2297537 2C/C + C/G genotype might be associated with a decreased risk of CC (OR = 0.71, 95% CI: 0.57-0.89) in the log-additive model. The rs2745709 T/T-C/C genotype might be associated with an increased risk of CC (OR = 1.44, 95% CI: 1.13-1.83) in the overdominant model. CONCLUSION: Our results indicate that rs2297538 and rs2297537 in miR-126, rs1292037 and rs13137 in miR-21, and rs2745709 in miR-221/222, may have important roles in the development of CIN or CC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasia Intraepitelial Cervical/patologia , Predisposição Genética para Doença , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero/patologia , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/genética , China/epidemiologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Genótipo , Humanos , Pessoa de Meia-Idade , Prognóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/genética
2.
Acta Cytol ; 65(5): 385-392, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34482310

RESUMO

OBJECTIVE: The objective of this study was to evaluate the application of DNA ploidy analysis in large-scale population screening for cervical cancer. METHODS: From March 2016 to March 2019, eligible subjects were enrolled and recommended to undergo DNA ploidy analysis, the ThinPrep cytology test (TCT), and high-risk human papillomavirus (hrHPV) detection concurrently. Patients with positive results were recommended for colposcopy, and biopsy diagnosis was regarded as the "gold standard." We compared the test efficiencies of the 3 methods and compared the efficiency and accuracy of the TCT in our hospital and the "2-cancer screening" project in Hubei Province during the same period. RESULTS: Among 20,574 women, the positive rates of DNA ploidy analysis, cytology, and hrHPV testing were 4.01%, 4.71%, and 16.28%, respectively. The sensitivities of these methods for screening for grade 2+ cervical intraepithelial neoplasia were 0.70, 0.68, and 0.96, and their specificities were 0.79, 0.82, and 0.45, respectively. On comparing DNA ploidy analysis with the TCT, there was no significant difference in the sensitivity, specificity, positive predictive value, negative predictive value, and missed diagnosis rate. In opportunistic screening and the 2-cancer screening project, the positive rates of cytology were 4.71% and 2.87%, respectively. And the efficiency and accuracy of the TCT in opportunistic screening were higher than in the 2-cancer screening project. CONCLUSION: Therefore, DNA ploidy analysis, which is of low-cost and does not depend on cytopathologists, can replace cytology and be applied in large-scale population screening for cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/genética , Programas de Rastreamento , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Adulto , Biópsia , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Citodiagnóstico/métodos , DNA , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Papillomaviridae/genética , Gravidez , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia , Adulto Jovem
3.
Cancer Sci ; 112(9): 3691-3698, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34252250

RESUMO

In Japan, the age-adjusted incidence of cervical cancer has been increasing constantly and rapidly among younger women. We set out to accurately confirm the effectiveness of the HPV vaccine in Japan. Data were collected for women born in the fiscal year (FY) 1990 to 1997, who became eligible for their 20-y-old cervical cancer screening between the FY 2010 to 2017. The adjusted incidence of cervical intraepithelial neoplasia (CIN)1+ in women born in FY 1990 to 1993, that is those who reached the national vaccination target age prior to the introduction of publicly subsidized HPV vaccinations, referred here after as "the pre-introduction generation", was 1.42% (242/17 040). The incidence in the "vaccination generation" (women born in FY 1994 to 1997, that is those who were heavily vaccinated as a group when they were of the nationally targeted age of 13-16) was 1.66% (135/8020). There was no significant difference between these incidence rates. However, our FY birth year-by-year analysis revealed that the incidence of CIN1+ was obviously lower than that predicted based on just the trend for CIN1+ seen in the pre-introduction generation. Our analysis revealed that the incidence of CIN3+ was obviously lower in the vaccination generation than in the pre-introduction generation (P = .0008). The incidence of CIN was already tending to increase in both the pre-introduction and vaccination generations. The changes in CIN incidence by individual birth FY must be examined to accurately determine the actual effects of the HPV vaccine for reducing mild cervical lesions.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Papillomaviridae/imunologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Vacinação/métodos , Adolescente , Neoplasia Intraepitelial Cervical/patologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Infecções por Papillomavirus/virologia , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Adulto Jovem
4.
Medicine (Baltimore) ; 100(28): e26593, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260540

RESUMO

ABSTRACT: Human papillomavirus (HPV) infection is a common sexually transmitted disease worldwide and the leading cause of cervical cancer. Current vaccines do not cover all HPV genotypes whereas the distribution of HPV genotypes varies in different geographic regions. The study aimed to investigate the distribution of HPV genotypes in patients with cervical squamous intraepithelial lesion (SIL) and cervical squamous cell carcinoma (SCC) in Taizhou City of Jiangsu Province, China. A total of 940 patients including 489 cases with cervical low-grade squamous intraepithelial lesions (LSIL), 356 cases with cervical high-grade squamous intraepithelial lesions (HSIL), and 95 cases with cervical SCC, underwent a biopsy or surgery in Taizhou People's Hospital between January 2019 and December 2019. The HPV testing results were retrospectively analyzed. The overall prevalence of any, high-risk, and low-risk HPV was 83.83%, 81.91%, and 12.13%, respectively. The 5 most common HPV genotypes were HPV16 (35.64%), HPV52 (16.91%), HPV58 (13.94%), HPV33 (8.94%), and HPV18 (7.98%). The prevalence of any and HR-HPV in SCC was significantly higher than those in LSIL and HSIL, while the prevalence of LR-HPV in SCC was significantly lower than those in LSIL and HSIL (P < .01). Single and dual HPV infections were prevalent in SCC, LSIL, and HSIL. Furthermore, the prevalence of dual HPV infection in SCC was significantly higher than those in LSIL and HSIL (P = .002). The HPV prevalence varied by age, being highest among women with SCC, LSIL, and HSIL aged 40 to 49 years, 40 to 49 years, and 50 to 59 years, respectively. In conclusion, the findings revealed a very high prevalence of HPV in women with cervical lesions in Taizhou. Routine HPV tests must cover all common HPV genotypes in clinical practice.


Assuntos
Alphapapillomavirus/genética , Carcinoma de Células Escamosas/virologia , Neoplasia Intraepitelial Cervical/virologia , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/virologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Neoplasia Intraepitelial Cervical/patologia , China/epidemiologia , DNA Viral , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Prevalência , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , Adulto Jovem
5.
Acta Cytol ; 65(5): 448-452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34293740

RESUMO

INTRODUCTION: Seborrheic keratosis-like lesion of the cervix and vagina is a rare lesion and shows similar morphology to vulvar seborrheic keratosis; 3 of the 7 previously reported cases were associated with low-risk human papillomavirus (HPV) type 42. We report a case of seborrheic keratosis-like lesion of the cervix and provide the first description of the cytological features of this lesion. CASE PRESENTATION: A woman in her late forties presented with postcoital bleeding. She had a cervical screening test following which she underwent cervical biopsy, endocervical and endometrial curettage, large loop excision of the transformation zone of the cervix, and hysterectomy. RESULTS: The liquid-based cytology preparation showed cohesive groups of mildly atypical squamoid cells with a spindle cell morphology, mildly increased nuclear to cytoplasmic ratio, prominent nucleoli, and occasional nuclear grooves. No koilocytes were identified. Molecular genotyping revealed positivity for HPV type 42. DISCUSSION/CONCLUSION: This represents the first description of the cytological features of a seborrheic keratosis-like lesion of the cervix, which are distinctive and unusual. Whilst the mild squamous atypia raised the possibility of a low-grade squamous intraepithelial lesion, no koilocytes were identified. The association in our case with a low-risk HPV type, HPV 42, provides further evidence for a role of this HPV type in the pathogenesis of these lesions.


Assuntos
Colo do Útero/patologia , Ceratose Seborreica/cirurgia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/cirurgia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/cirurgia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Ceratose Seborreica/complicações , Ceratose Seborreica/patologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Risco , Lesões Intraepiteliais Escamosas/cirurgia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/patologia
6.
Acta Cytol ; 65(5): 377-384, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34077926

RESUMO

Sweden has experienced an unexpected >30% increase in cervical cancer incidence among women with normal cytological screening results. We therefore performed a nationwide assessment of false-negative cytology before invasive cervical cancer. The Swedish national cervical screening registry identified 2,150 normal cytologies taken up to 10 years before 903 cases of invasive cervical cancer. The 27 cytological laboratories in Sweden were asked to rereview the slides, and all of them completed the rereview. One thousand nine hundred fifteen slides were retrieved and reviewed. Abnormalities were found in 30% of the slides, and the proportion of slides that had a changed diagnosis on rereview increased on average by 3.9% per sampling year during 2001-2016 (p < 0.03). We also asked for rereview of normal smears taken up to 42 months before a histopathologically diagnosed high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS). 19/27 laboratories responded, and out of 6,101 normal smears taken before HSIL/AIS, 5,918 were retrieved and rereviewed. The diagnosis was changed in 25% of cases. In summary, we found an increasing time trend of false-negative smears taken before invasive cervical cancer. This indicates a decreased protection of normal cytology in the screening program supporting earlier findings that this is the main reason behind the recent Swedish increase in cervical cancer. We suggest that optimal cervical cancer control may be promoted by routine nationally coordinated rereview of negative smears before high-grade cervical lesions or invasive cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Detecção Precoce de Câncer , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Esfregaço Vaginal
7.
PLoS Med ; 18(6): e1003665, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34086680

RESUMO

BACKGROUND: Excisional procedures of cervical intraepithelial neoplasia (CIN) may increase the risk of preterm birth. It is unknown whether this increased risk is due to the excision procedure itself, to the underlying CIN, or to secondary risk factors that are associated with both preterm birth and CIN. The aim of this study is to assess the risk of spontaneous preterm birth in women with treated and untreated CIN and examine possible associations by making a distinction between the excised volume of cervical tissue and having cervical disease. METHODS AND FINDINGS: This Dutch population-based observational cohort study identified women aged 29 to 41 years with CIN between 2005 and 2015 from the Dutch pathology registry (PALGA) and frequency matched them with a control group without any cervical abnormality based on age at and year of pathology outcome (i.e., CIN or normal cytology) and urbanization (<100,000 inhabitants or ≥100,000 inhabitants). All their 45,259 subsequent singleton pregnancies with a gestational age ≥16 weeks between 2010 and 2017 were identified from the Dutch perinatal database (Perined). Nineteen potential confounders for preterm birth were identified. Adjusted odds ratios (ORs) were calculated for preterm birth comparing the 3 different groups of women: (1) women without CIN diagnosis; (2) women with untreated CIN; and (3) women with treated CIN prior to each childbirth. In total, 29,907, 5,940, and 9,412 pregnancies were included in the control, untreated CIN, and treated CIN group, respectively. The control group showed a 4.8% (1,002/20,969) proportion of spontaneous preterm birth, which increased to 6.9% (271/3,940) in the untreated CIN group, 9.5% (600/6,315) in the treated CIN group, and 15.6% (50/321) in the group with multiple treatments. Women with untreated CIN had a 1.38 times greater odds of preterm birth compared to women without CIN (95% confidence interval (CI) 1.19 to 1.60; P < 0.001). For women with treated CIN, these odds 2.07 times increased compared to the control group (95% CI 1.85 to 2.33; P < 0.001). Treated women had a 1.51 times increased odds of preterm birth compared to women with untreated CIN (95% CI 1.29 to 1.76; P < 0.001). Independent from cervical disease, a volume excised from the cervix of 0.5 to 0.9 cc increased the odds of preterm birth 2.20 times (37/379 versus 1,002/20,969; 95% CI 1.52 to 3.20; P < 0.001). These odds further increased 3.13 times and 5.93 times for women with an excised volume of 4 to 8.9 cc (90/724 versus 1,002/20,969; 95% CI 2.44 to 4.01; P < 0.001) and ≥9 cc (30/139 versus 1,002/20,969; 95% CI 3.86 to 9.13; P < 0.001), respectively. Limitations of the study include the retrospective nature, lack of sufficient information to calculate odds of preterm birth <24 weeks, and that the excised volume could only be calculated for a select group of women. CONCLUSIONS: In this study, we observed a strong correlation between preterm birth and a volume of ≥0.5 cc excised cervical tissue, regardless of the severity of CIN. Caution should be taken when performing excisional treatment in women of reproductive age as well as prudence in case of multiple biopsies. Fertile women with a history of performing multiple biopsies or excisional treatment for CIN may benefit from close surveillance during pregnancy.


Assuntos
Adenocarcinoma in Situ/epidemiologia , Neoplasia Intraepitelial Cervical/epidemiologia , Nascimento Prematuro/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adenocarcinoma in Situ/patologia , Adenocarcinoma in Situ/cirurgia , Adulto , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/cirurgia , Bases de Dados Factuais , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Países Baixos/epidemiologia , Gravidez , Resultado da Gravidez , Nascimento Prematuro/diagnóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
8.
Obstet Gynecol ; 137(6): 1043-1053, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33957649

RESUMO

OBJECTIVE: To evaluate the histologic response rate of high-grade squamous intraepithelial lesions (HSIL) of the cervix after topical application of 5% imiquimod cream. METHODS: In this phase II trial, women with cervical HSIL (cervical intraepithelial neoplasia [CIN] 2-3) were randomly assigned to 250 mg of 5% imiquimod cream applied to the cervix weekly for 12 weeks, followed by loop electrosurgical excision procedure (LEEP) without preceding treatment. The sample size was calculated based on the HSIL regression rates previously reported by Grimm et al. The primary outcome was rate of histologic regression (to CIN 1 or less) in LEEP specimens. Prespecified secondary endpoints included surgical margin status and adverse events. Outcomes were stratified by human papillomavirus type and lesion grade (CIN 2 or CIN 3). Results were reported according to per protocol (PP) and intention-to-treat (ITT) analyses. RESULTS: Ninety women were enrolled: 49 in the experimental group and 41 in the control group. In the PP population, histologic regression was observed in 23 of 38 participants (61%) in the experimental group compared with 9 of 40 (23%) in the control group (P=.001). Surgical margins were negative for HSIL in 36 of 38 participants (95%) in the experimental group and 28 of 40 (70%) in the control group (P=.004). In the ITT population, rates of histologic regression also were significantly higher in the experimental group. Rates of adverse events in the experimental group were 74% (28/38) in the PP population and 78% (35/45) in the ITT population. Adverse events were mild, with abdominal pain being the most common. Three patients in the experimental group had grade 2 adverse events, including vaginal ulcer, vaginal pruritus with local edema, and moderate pelvic pain. CONCLUSION: Weekly topical treatment with imiquimod is effective in promoting regression of cervical HSIL. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03233412.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasia Intraepitelial Cervical/tratamento farmacológico , Imiquimode/uso terapêutico , Lesões Intraepiteliais Escamosas Cervicais/tratamento farmacológico , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/tratamento farmacológico , Administração Tópica , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/cirurgia , Terapia Combinada , Eletrocirurgia , Feminino , Humanos , Imiquimode/administração & dosagem , Imiquimode/efeitos adversos , Análise de Intenção de Tratamento , Margens de Excisão , Pessoa de Meia-Idade , Gradação de Tumores , Infecções por Papillomavirus/virologia , Lesões Intraepiteliais Escamosas Cervicais/cirurgia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem
9.
Biomed Res Int ; 2021: 6650966, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954190

RESUMO

New prevention strategies are needed to detect cervical intraepithelial neoplasia (CIN). The microRNA expression analysis has already been reported as molecular biomarkers in the early detection of cervical cancer (CC) through minimally invasive samples, such as liquid biopsy, obtained through collection using liquid-based cytology (LBC). In this study, we aimed to identify molecular signatures of microRNAs in cervical precursor lesions from LBC cervical and the molecular pathways potentially associated with the CC progression. We analyzed 31 LBC cervical samples from women who underwent colposcopy. These samples were divided into two groups: the first group was composed of samples without precursor lesions of CC, considering the control group, referred to as healthy female subjects (HFS; n = 11). The second group corresponded to women diagnosed with cervical interepithelial neoplasia grade 3 (CIN 3; n = 20). We performed microRNA and gene expression profiling using the nCounter® miRNA Expression Assays (NanoString Technology) and PanCancer Pathways (NanoString Technology), respectively. A microRNA target prediction was performed by mirDIP, and molecular pathway interaction was constructed using Cytoscape. Bidirectional in silico analyses and Pearson's correlation were performed for associated the relation between genes, and miRNAs differentially expressed related cervical cancer progression were performed. We found that the expression of nine microRNAs was significantly higher, two were downregulated (miR-381-3p and miR-4531), and seven miRNAs were upregulated (miR-205-5p, miR-130a-3p, miR-3136-3p, miR-128-2-5p, let-7f-5p, miR-202-3p, and miR-323a-5p) in CIN 3 (fold change ≥ 2 and p ≤ 0.05). The miRNA expression patterns were independent of hr-HPV infection. We identified four miRNAs (miR-205-5p, miR-130a-3p, miR-4531, and miR-381-3p) that could be used as biomarkers for CIN 3 in LBC samples through multiple logistic regression analyses. We found 16 genes differentially expressed between CIN 3 and HSF samples (fold change ≥ 2 and p ≤ 0.05). We found the correlation between miR-130a-3p and CCND1(R = -0.52; p = 0.0029), miR-205-5p and EGFR (R = 0.53; p = 0.0021), and miR-4531 and SMAD2 (R = -0.54; p = 0.0016). In addition, we demonstrated the most significant pathways of the targets associated with cervical cancer progression (FDR-corrected p < 0.001). This study demonstrated that miRNA biomarkers may distinguish healthy cervix and CIN 3 and regulate important molecular pathways of carcinogenesis.


Assuntos
Biomarcadores Tumorais/genética , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Área Sob a Curva , Biomarcadores Tumorais/metabolismo , Neoplasia Intraepitelial Cervical/virologia , Simulação por Computador , Regulação para Baixo/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Biópsia Líquida , Modelos Logísticos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Infecções por Papillomavirus/complicações , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Risco , Regulação para Cima/genética , Neoplasias do Colo do Útero/virologia , Adulto Jovem
10.
Acta Cytol ; 65(3): 264-271, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33951624

RESUMO

INTRODUCTION: Alternative methods of dry storage and transportation may be a viable alternative to the use of liquid storage medium for cervical samples, especially for screening programs in places with few resources. OBJECTIVE: The objective of this study is to verify the viability and efficacy of human papillomavirus DNA (HPV-DNA) detection in cervical cell samples collected and stored on a Flinders Technology Associates (FTA) card (Whatman Indicating FTA® Elute Micro Card) and subsequently recovered in ethanol-based liquid medium and to compare the results to those obtained using samples stored directly in ethanol-based liquid medium. STUDY DESIGN: Thirty-four women submitted to ETZ (excision of the transformation zone of the cervix) were included in this study. Before ETZ, 2 samples of exfoliated cervical cells were collected from each woman by a doctor and stored in ethanol-based liquid medium and on an FTA card. DNA recovery from FTA samples was performed using ethanol-based liquid medium. Detection of HPV-DNA in the samples was performed using the Cobas® 4800 HPV Test Platform. RESULTS AND CONCLUSIONS: The HPV-DNA detection positivity rates were 70.6% for the samples collected directly in liquid medium and 64.7% for the samples stored on the FTA card, with high detection accuracy in the DNA samples recovered from the FTA card (area under the curve = 0.958; 95% confidence interval = 0.890-1.000). The concordance between the results obtained using the 2 storage media was 94.1% (Kappa = 0.866). These preliminary results suggest that collection of cervical material on an FTA card may be an alternative to storage in liquid medium since the liquid medium has some limitations. In addition, DNA recovery from the card using ethanol-based liquid medium streamlines the workflow in the laboratory and reduces the cost associated with reagents, thereby facilitating access to the HPV test in places with few resources and potentially improving cervical cancer screening.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , DNA Viral/isolamento & purificação , Etanol , Filtração/instrumentação , Testes de DNA para Papilomavírus Humano , Papel , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Manejo de Espécimes/instrumentação , Neoplasias do Colo do Útero/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , DNA Viral/genética , Feminino , Humanos , Gradação de Tumores , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Projetos Piloto , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
11.
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
12.
Medicine (Baltimore) ; 100(20): e26004, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011097

RESUMO

BACKGROUND: Early detection and diagnosis of high-grade cervical intraepithelial neoplasia grade 2 or higher (CIN2+) is critical for a good prognosis and appropriate treatment. The chief aim of our study was to evaluate the diagnostic performance of folate receptor-mediated staining solution detection (FRD) for CIN2+. METHODS: We conducted a systematic review and meta-analysis by searching the PubMed and EMBASE databases for studies published until May 2020, which assessed the diagnostic accuracy of FRD, human papilloma virus (HPV) testing, and ThinPrep cytology test (TCT) for the detection of CIN2+. Bivariate models were used to compare the diagnostic performance of FRD, HPV, and TCT. RESULTS: Six studies involving 2817 patients were included in this meta-analysis. The pooled specificity of FRD was higher than that of HPV and TCT for detecting CIN2+ (0.65, 0.12, and 0.39, respectively). The summary area under the receiver operating characteristic curve values using FRD, HPV, and TCT for detecting CIN2+ were 0.79, 0.95, and 0.77, respectively, indicating that FRD was superior to TCT. The diagnostic odds ratios of FRD, HPV, and TCT were 6 (95% CI: 5-7), 3 (95% CI: 2-5), and 3 (95% CI: 2-4), respectively, demonstrating that FRD had good diagnostic accuracy. CONCLUSION: FRD showed good diagnostic accuracy and higher specificity than HPV and TCT for detecting CIN2+. Based on our results, we propose that FRD could be a candidate for cervical screening, especially in underdeveloped countries.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Detecção Precoce de Câncer/métodos , Infecções por Papillomavirus/diagnóstico , Coloração e Rotulagem/métodos , Neoplasias do Colo do Útero/diagnóstico , Alphapapillomavirus , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/patologia , Colo do Útero/virologia , Feminino , Receptor 1 de Folato/metabolismo , Ácido Fólico/química , Ácido Fólico/metabolismo , Humanos , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos
13.
Medicine (Baltimore) ; 100(20): e26030, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011112

RESUMO

ABSTRACT: To explore the optimal way to manage patients with high-grade squamous intraepithelial lesion (HSIL) and positive margin by identifying the risk factors for its recurrence and residue.A retrospective study was conducted on 267 cases of a pathologically confirmed HSIL with positive margin following conization by loop electrosurgical excisional procedure (LEEP) between January 2010 and December 2015. One hundred two cases were selected for regular follow-up every 6 months, and 165 cases were selected for a second surgery (repeat cervical conization or hysterectomy) within 3 months of initial LEEP. We analyzed the association between recurrent or residual diseases and these factors: age, menopausal status, ThinPrep cytologic test (TCT) results, high-risk human papillomavirus (HR-HPV) infection, pathological grades of the margin, number of involved margins, and glandular involvement.The recurrence rate among 102 cases who underwent follow-up was 17.6% (18/102). The factors: atypical squamous cells of undetermined significance cannot exclude HSIL (ASC-H) or higher lesions in the pre-LEEP TCT (P = .038), persistent HR-HPV infection at the 6th month post-LEEP (P = .03), HSIL-positive margin (P = .003), and multifocal-involved margin (P = .002) were significantly associated with recurrent disease, while age, menopause, and pre-LEEP HR-HPV infection were not associated with recurrent disease (P > .05). The residual rate among 165 patients who underwent a second surgery was 45.5% (75/165), of which 15 cases were residual cervical cancer. The factors: menopause (P = .02), ≥ASC-H in pre-LEEP TCT (P = .04), pre-LEEP HR-HPV infection (P = .04), ≥HSIL-positive margin (P < .001), and multifocal-involved margin (P < .001) significantly increased the risk of residual disease. No correlation existed between residual disease and age or glandular involvement (P > .05).For patients with a positive margin after LEEP, regular follow-up or second surgery should be selected according to fertility requirement and pathological characteristics of the positive margin, as well as TCT and HR-HPV infection condition.


Assuntos
Neoplasia Intraepitelial Cervical/cirurgia , Conização , Eletrocirurgia , Lesões Intraepiteliais Escamosas Cervicais/cirurgia , Neoplasias do Colo do Útero/cirurgia , Neoplasia Intraepitelial Cervical/patologia , Feminino , Humanos , Margens de Excisão , Pessoa de Meia-Idade , Neoplasia Residual , Estudos Retrospectivos , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/patologia
14.
Am J Obstet Gynecol ; 225(3): 278.e1-278.e16, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33852886

RESUMO

BACKGROUND: An increase in human papillomavirus test volumes is expected in the near future because human papillomavirus-based screening protocols are expected to become more widely adopted. OBJECTIVE: The IMproving Primary Screening And Colposcopy Triage trial, a prospective, multicenter, US-based cervical cancer screening trial, was conducted to obtain US Food and Drug Administration approvals for the new, high-throughput cobas human papillomavirus (cobas HPV) test for use on the cobas 6800/8800 Systems (cobas HPV) for detecting cervical precancerous and cancerous cells (cervical intraepithelial neoplasia of grade 2 or worse and grade 3 or worse). Here, the baseline demographics, human papillomavirus test results, cervical cytology, and histopathologic results are presented. In addition, the baseline and 1-year risks of cervical intraepithelial neoplasia grade 2 or worse and grade 3 or worse associated with the human papillomavirus results are reported. STUDY DESIGN: In total, 35,263 women aged between 25 and 65 years undergoing routine screening were enrolled; liquid-based cytology and 2 polymerase chain reaction-based tests for high-risk human papillomavirus were performed. Women with abnormal Papanicolaou cytology, women positive for high-risk human papillomavirus by either of the 2 human papillomavirus tests, and a random subset of women negative according to the Papanicolaou cytology and the 2 human papillomavirus tests were referred for a colposcopy and cervical biopsy. Women who did not meet the study endpoint were eligible for the 1-year follow-up study phase. Verification bias-adjusted cervical disease prevalence and risks and 95% confidence intervals were computed. RESULTS: The prevalence of atypical squamous cells of undetermined significance and worse than atypical squamous cells of undetermined significance cytology were 6.5% and 3.2%, respectively. Prevalence of high-risk human papillomavirus, human papillomavirus 16, and human papillomavirus 18 based on the new cobas HPV test were 15.1%, 3.1%, and 1.4%, respectively. Both cytologic abnormalities and human papillomavirus positivity declined with increasing age. Among women who had a colposcopy and biopsy, the prevalence of cervical intraepithelial neoplasia grade 2 or worse and grade 3 or worse were 8.8% and 3.6%, respectively. The baseline and 1-year cumulative risks for cervical intraepithelial neoplasia grade 3 or worse were 13.6% and 16.9%, respectively, among women who tested positive for human papillomavirus 16. Women who tested negative for human papillomavirus had the lowest 1-year cumulative risk for cervical intraepithelial neoplasia grade 3 or worse (0.06%). CONCLUSION: The contemporary, age-specific prevalence of human papillomaviruses (including human papillomavirus 16 and 18), cytologic abnormalities, and cervical intraepithelial neoplasia in a large, US-based cervical cancer screening population provides benchmarks for healthcare policies, screening programs, and for laboratories and clinicians.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Colposcopia , Detecção Precoce de Câncer , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Biópsia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
15.
Lancet Oncol ; 22(4): 548-557, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33794208

RESUMO

BACKGROUND: Most uterine cervical high-risk human papillomavirus (HPV) infections are transient, with only a small fraction developing into cervical cancer. Family aggregation studies and heritability estimates suggest a significant inherited genetic component. Candidate gene studies and previous genome-wide association studies (GWASs) report associations between the HLA region and cervical cancer. Adopting a genome-wide approach, we aimed to compare genetic variation in women with invasive cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 with that in healthy controls. METHODS: We did a GWAS in a cohort of unrelated European individuals using data from UK Biobank, a population-based cohort including 273 377 women aged 40-69 years at recruitment between March 13, 2006, and Oct 1, 2010. We used an additive univariate logistic regression model to analyse genetic variants associated with invasive cervical cancer or CIN3. We sought replication of candidate associations in FinnGen, a large independent dataset of 128 123 individuals. We also did a two-sample mendelian randomisation approach to explore the role of risk factors in the genetic risk of cervical cancer. FINDINGS: We included 4769 CIN3 and invasive cervical cancer case samples and 145 545 control samples in the GWAS. Of 9 600 464 assayed and imputed single-nucleotide polymorphisms (SNPs), six independent variants were associated with CIN3 and invasive cervical cancer. These included novel loci rs10175462 (PAX8; odds ratio [OR] 0·87, 95% CI 0·84-0·91; p=1·07 × 10-9) and rs27069 (CLPTM1L; 0·88, 0·84-0·92; p=2·51 × 10-9), and previously reported signals at rs9272050 (HLA-DQA1; 1·27, 1·21-1·32; p=2·51 × 10-28), rs6938453 (MICA; 0·79, 0·75-0·83; p=1·97 × 10-17), rs55986091 (HLA-DQB1; 0·66, 0·60-0·72; p=6·42 × 10-28), and rs9266183 (HLA-B; 0·73, 0·64-0·83; p=1·53 × 10-6). Three SNPs were replicated in the independent Finnish dataset of 1648 invasive cervical cancer cases: PAX8 (rs10175462; p=0·015), CLPTM1L (rs27069; p=2·54 × 10-7), and HLA-DQA1 (rs9272050; p=7·90 × 10-8). Mendelian randomisation further supported the complementary role of smoking (OR 2·46, 95% CI 1·64-3·69), older age at first pregnancy (0·80, 0·68-0·95), and number of sexual partners (1·95, 1·44-2·63) in the risk of developing cervical cancer. INTERPRETATION: Our results provide new evidence for the genetic susceptibility to cervical cancer, specifically the PAX8, CLPTM1L, and HLA genes, suggesting disruption in apoptotic and immune function pathways. Future studies integrating host and viral, genetic, and epigenetic variation, could further elucidate complex host-viral interactions. FUNDING: NIHR Imperial BRC Wellcome 4i Clinician Scientist Training Programme.


Assuntos
Neoplasia Intraepitelial Cervical/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Fator de Transcrição PAX8/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Neoplasia Intraepitelial Cervical/patologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Antígenos HLA/genética , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Neoplasias do Colo do Útero/patologia
16.
Int J Cancer ; 149(3): 707-716, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33729551

RESUMO

High-grade cervical intraepithelial neoplasia (CIN2 and CIN3) represents a heterogeneous disease with varying cancer progression risks. Biomarkers indicative for a productive human papillomavirus (HPV) infection (HPV E4) and a transforming HPV infection (p16ink4a , Ki-67 and host-cell DNA methylation) could provide guidance for clinical management in women with high-grade CIN. This study evaluates the cumulative score of immunohistochemical expression of p16ink4a (Scores 0-3) and Ki-67 (Scores 0-3), referred to as the "immunoscore" (IS), in 262 CIN2 and 235 CIN3 lesions derived from five European cohorts in relation to immunohistochemical HPV E4 expression and FAM19A4/miR124-2 methylation in the corresponding cervical scrape. The immunoscore classification resulted in 30 lesions within IS group 0-2 (6.0%), 151 lesions within IS group 3-4 (30.4%) and 316 lesions within IS group 5-6 (63.6%). E4 expression decreased significantly from CIN2 to CIN3 (P < .001) and with increasing immunoscore group (Ptrend < .001). Methylation positivity increased significantly from CIN2 to CIN3 (P < .001) and with increasing immunoscore group (Ptrend < .001). E4 expression was present in 9.8% of CIN3 (23/235) and in 12.0% of IS group 5-6 (38/316). Notably, in a minority (43/497, 8.7%) of high-grade lesions, characteristics of both transforming HPV infection (DNA hypermethylation) and productive HPV infection (E4 expression) were found simultaneously. Next, we stratified all high-grade CIN lesions, based on the presumed cancer progression risk of the biomarkers used, into biomarker profiles. These biomarker profiles, including immunoscore and methylation status, could help the clinician in the decision for immediate treatment or a "wait and see" policy to reduce overtreatment of high-grade CIN lesions.


Assuntos
Neoplasia Intraepitelial Cervical/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Citocinas/metabolismo , Metilação de DNA , Antígeno Ki-67/metabolismo , MicroRNAs/genética , Proteínas Oncogênicas Virais/metabolismo , Neoplasias do Colo do Útero/patologia , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasia Intraepitelial Cervical/classificação , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Citocinas/genética , Gerenciamento Clínico , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Antígeno Ki-67/genética , Proteínas Oncogênicas Virais/genética , Prognóstico , Estudos Prospectivos , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo
17.
Am J Clin Pathol ; 156(4): 569-576, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-33728437

RESUMO

OBJECTIVES: This study examined the association of high-risk human papillomavirus (hrHPV) status and HPV genotype with histopathologic follow-ups in women with an atypical glandular cell (AGC) interpretation. METHODS: Cases with AGC interpretation on a Papanicolaou (Pap) test were retrieved along with hrHPV testing, genotyping, and histologic follow-up results if available. RESULTS: A total of 561 AGC cases were identified, with histologic follow-up available for 471 cases (84%). The follow-up diagnoses included benign or reactive changes (60% of cases), low-grade cervical intraepithelial neoplasia (18%), high-grade cervical intraepithelial neoplasia (CIN2-3; 7%), cervical carcinoma (5%), and other malignancies (10%). Tests for hrHPV were positive in 128 of 426 (30%) cases, including HPV16 (30%), HPV18 (14%) and other HPV subtypes (56%). A positive hrHPV result significantly increased the risk of developing CIN2-3 or cervical carcinoma (odds ratio, 24.6; 95% CI, 9.9-58.9) and HPV16 or HPV18 further increased the risk (odds ratio, 49.5; 95% CI, 17.7-123.7). CONCLUSIONS: Our data demonstrate that in women with an AGC Pap interpretation, a positive hrHPV result, especially type 16 or 18, is associated with an increased risk of developing cervical CIN2-3 or higher lesions, suggesting potential implications of hrHPV testing for the management of patients with an AGC result on a Pap test.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/patologia , Feminino , Seguimentos , Genótipo , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Risco , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
18.
Cancer Med ; 10(8): 2668-2679, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33710792

RESUMO

Methylation biomarkers are promising tools for diagnosis and disease prevention. The S5 classifier is aimed at the prevention of cervical cancer by the early detection of cervical intraepithelial neoplasia (CIN). S5 is based on pyrosequencing a promoter region of EPB41L3 and five late regions of HPV types 16, 18, 31, and 33 following bisulfite conversion of DNA. Good biomarkers should perform well in a variety of sample types such as exfoliated cells, fresh frozen or formalin-fixed paraffin-embedded (FFPE) materials. Here, we tested the performance of S5 on 315 FFPE biopsies with paired exfoliated cervical samples using four different conversion kits (Epitect Bisulfite, Epitect Fast Bisulfite, EZ DNA Methylation, and EZ DNA Methylation-Lightning). The S5 values from FFPE biopsies for all kits were significantly correlated with those obtained from their paired exfoliated cells. For the EZ DNA Methylation kit, we observed an average increased methylation of 4.4% in FFPE. This was due to incomplete conversion of DNA (73% for FFPE vs. 95% for cells). The other kits had a DNA conversion rate in FFPE similar to the cells (95%-97%). S5 performed well at discriminating

Assuntos
Neoplasia Intraepitelial Cervical/patologia , Metilação de DNA , Neoplasias do Colo do Útero/patologia , Adolescente , Adulto , Idoso , Alphapapillomavirus/genética , Área Sob a Curva , Biópsia/métodos , Neoplasia Intraepitelial Cervical/genética , Colposcopia , Feminino , Formaldeído , Humanos , Proteínas dos Microfilamentos/genética , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Sensibilidade e Especificidade , Sulfitos , Fixação de Tecidos , Neoplasias do Colo do Útero/genética , Adulto Jovem
19.
Gynecol Oncol ; 161(2): 429-435, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33757653

RESUMO

OBJECTIVE: Human papillomavirus (HPV) testing as the primary cervical cancer screening followed by reflex cytology if high-risk HPV is present (hrHPV+) is recently adopted in some countries. However, reflex cytology's sensitivity is variable, and a suitable triage approach for hrHPV+ remains controversial. Here, we compared the performance of three triage tools in hrHPV+ women. METHODS: Three triage tools-cytology, HPV16/18 genotyping, and DNA methylation biomarker PAX1m-were analyzed for their clinical performance in hrHPV+ women. In addition, women without cervical cancer at enrollment were followed for histologically confirmed high-grade cervical intraepithelial neoplasia or worse (CIN3+) annually using Papanicolaou smear. RESULTS: Of 4762 women aged ≥20 years enrolled, 502 (10.5%) were hrHPV+. PAX1m and cytology demonstrated similar accuracy (>90%), sensitivity (>78%), and specificity (>92%) as triage tools in 429 hrHPV+ women aged 30-64 years. PAX1m had better accuracy and specificity (91.6% and 92.5%, respectively) than HPV16/18 (76.9% and 76.8%, respectively). The incidence of CIN3+ among hrHPV+ women was 10.7 cases/1000 person-years. The incidence was significantly greater in PAX1m-positive women than in PAX1m-negative women. CONCLUSIONS: PAX1m has comparable clinical performance to cytology and better accuracy and specificity than HPV16/18 as the triage tool for detecting CIN3+ in hrHPV+ women. The PAX1m assay is thus a promising molecular-based triage tool for early detection of CIN and predicting disease progression in hrHPV+ women. It can be especially useful in countries where adequate cytology-based infrastructure is lacking, such as some Southeast Asian countries, for cervical cancer screening and prevention.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Detecção Precoce de Câncer/métodos , Fatores de Transcrição Box Pareados/genética , Infecções por Papillomavirus/diagnóstico , Triagem/métodos , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virologia , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Progressão da Doença , Feminino , Seguimentos , Técnicas de Genotipagem , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Sensibilidade e Especificidade , Taiwan , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia
20.
PLoS One ; 16(3): e0248639, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33750983

RESUMO

Persistent infection by high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer and its precursor lesions. While some cytokines help immune cells in virus clearance, others contribute to the persistence of infection and neoplastic progression. Here, the levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-6, IL-4, and IL-2 were quantified in the serum and exfoliated cervical cells (ECCs) of patients with HR-HPV, and the presence of IL-6+ cells was investigated in uterine cervix biopsies. Cytokine levels in the serum and ECCs of 26 HR-HPV DNA-positive patients and 18 HPV DNA-negative patients were measured using flow cytometry. Fifteen uterine cervix biopsy samples embedded in paraffin were subjected to immunohistochemical analysis for the detection of IL-6+ cells. HR-HPV-positive patients showed increased IL-6 and IL-10 in the ECCs and serum, respectively. Compared with HPV DNA-positive patients, HPV DNA-negative patients had higher levels of IL-6 in ECCs. Patients with multiple infections of HPV had higher levels of IL-6 in their ECCs than those with a single infection. Immunostaining of uterine cervix biopsy samples revealed no differences in IL-6 expression between the different classes of histopathological lesions. However, differences were observed in the expression levels of IL-6 and IL-10 at the systemic and local levels in HR-HPV-positive patients without cervical lesions. Considering the functional characteristics of these cytokines, it can be inferred that such patients are prone to persistent HPV infection.


Assuntos
Neoplasia Intraepitelial Cervical/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Infecções por Papillomavirus/sangue , Adulto , Idoso , Alphapapillomavirus/isolamento & purificação , Alphapapillomavirus/patogenicidade , Biópsia , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/patologia , Colo do Útero/virologia , DNA Viral/isolamento & purificação , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Fator de Necrose Tumoral alfa/sangue
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