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1.
Int J Cancer ; 152(2): 137-150, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35904861

RESUMO

Declines in cervical intraepithelial neoplasia grades 2 to 3 and adenocarcinoma in situ (CIN2+) observed among young women suggest impact from human papillomavirus (HPV) vaccination. To further evaluate vaccine impact including cross-protection and type replacement, we described high-risk (HR)-HPV type-specific cervical precancer incidence rates among women aged 20 to 39 years, 2008 to 2016. We analyzed cross-sectional population-based data on 18 344 cases of CIN2+ from a 5-site surveillance system. Diagnostic specimens were tested for individual HPV types, including 14 HR-HPV types (HPV16/18/31/33/35/39/45/51/52/56/58/59/66/68). We estimated age-specific annual HR-HPV type-specific CIN2+ incidence per 100 000 screened women for individual types, vaccine HR-HPV types (HPV16/18) and nonvaccine HR-HPV types (non-HPV16/18). We evaluated trends using average annual percent changes (AAPC) and 95% confidence intervals (CI), and estimated total declines by comparing 2015-2016 to 2008-2009 using incidence rate ratios. Among 20-24-year-olds, HPV16/18-CIN2+ declined from 2008 through 2016 (AAPC: -21.3%, 95% CI: -28.1%, -13.8%), whereas no trend was observed for non-HPV16/18-CIN2+ (AAPC: -1.8%, 95% CI: -8.1%, 4.9%). After 2010, CIN2+ among 20-24-year-olds was more often caused by nonvaccine vs vaccine HR-HPV types. No significant declining trends were observed in older age groups. In 2015-2016 compared with 2008-2009, HPV16-CIN2+ declined 78%, HPV18-CIN2+ 72% and HPV31-CIN2+ 51% among 20-24-year-olds; no increases were observed in type-specific CIN2+ incidence. Among 25-29-year-olds, HPV16-CIN2+ declined 18%; CIN2+ attributed to seven nonvaccine types increased significantly. No significant declines were observed in older groups. Significant declines in HPV16/18-CIN2+ in 20-24-year-olds and HPV16-CIN2+ in 25-29-year-olds corroborate impact of HPV vaccination. A declining trend in HPV31-CIN2+ is consistent with cross-protection from vaccination.


Assuntos
Neoplasia Intraepitelial Cervical , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Estados Unidos/epidemiologia , Idoso , Neoplasias do Colo do Útero/patologia , Estudos Transversais , Vacinas contra Papillomavirus/uso terapêutico , Papillomavirus Humano 16 , Papillomavirus Humano 31
2.
Ultrasound Med Biol ; 49(1): 375-379, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36283939

RESUMO

The aim of this study was to ascertain the safety of high-intensity focused ultrasound (HIFU) for high-grade cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) in patients with fertility requirements. This was a prospective one-arm study. Consecutive CIN 2/3 patients diagnosed with histopathology were screened, enrolled and treated from September 2019 to September 2020 in the Affiliated Hospital of North Sichuan Medical College. All patients were treated with a combination of HIFU and antiviral treatment with REBACIN. The scheduled follow-up visits were 1 week, 1 mo, 3 mo, 6 mo and 12 mo after surgery. The primary outcomes included cure and human papillomavirus clearance rates. We screened 287 consecutive CIN 2/3 patients in our hospital, 29 of whom were enrolled and treated in this study. The cure rate reached 82.8% at 7 mo after treatment and 96.6% within 1 y. The HPV-negative rate reached 72.4% (21/29) around 6 mo after treatment, with mild side effects during and after the procedure. Our study suggests that in CIN 2/3 study participants with fertility requirements, HIFU + REBACIN therapy is a safe and effective therapeutic option with a high cure rate, HPV clearance and few side effects.


Assuntos
Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasia Intraepitelial Cervical/cirurgia , Neoplasia Intraepitelial Cervical/diagnóstico , Infecções por Papillomavirus/terapia , Estudos Prospectivos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/cirurgia , Papillomaviridae
3.
Int J Cancer ; 152(2): 249-258, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35852007

RESUMO

We are reporting (a) updated incidence of cervical intraepithelial neoplasia (CIN) among women who did not have colposcopic or histopathological disease at baseline and (b) disease outcomes among women treated for CIN and their follow-up HPV status; in a cohort of women living with HIV (WHIV). The median overall follow-up was 3.5 years (IQR 2.8-4.3). The incidence of any CIN and that of CIN 2 or worse disease was 16.7 and 7.0 per 1000 person-years of observation (PYO), respectively. Compared with women who were HPV negative at baseline, women who cleared HPV infection had 23.95 times increased risk of incident CIN 2 or worse lesions (95% CI 2.40-661.07). Women with persistent HPV infection had 138.18 times increased risk of CIN 2 or worse lesions (95% CI 20.30-3300.22). Complete disease regression was observed in 65.6% of the HPV positive women with high-grade CIN and were treated with thermal ablation but HPV persistence was seen in 44.8% of those with high-grade disease. Among those who did not have any disease at baseline and were also HPV negative, about 87% (95% CI 83.79-89.48) women remained HPV negative during consecutive HPV test/s with the median interval of 3.5 years. Long-term surveillance of WHIV treated for any CIN is necessary for the prevention of cervical cancer among them. Our study provides an early indication that the currently recommended screening interval of 3 to 5 years among WHIV may be extended to at least 5 years among HPV negative women. Increasing the screening interval can be cost saving and improve scalability among WHIV to support WHO's cervical cancer elimination initiative.


Assuntos
Neoplasia Intraepitelial Cervical , Infecções por HIV , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Detecção Precoce de Câncer/efeitos adversos , Papillomaviridae , Estudos de Coortes , Índia/epidemiologia , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/patologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia
4.
Clin Epigenetics ; 14(1): 150, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36414968

RESUMO

BACKGROUND: Cervical screening using primary human papilloma virus (HPV) testing and cytology is being implemented in several countries. Cytology as triage for colposcopy referral suffers from several shortcomings. HPV testing overcomes some of these but lacks specificity in women under 30. Here, we aimed to develop and validate an automatable triage test that is highly sensitive and specific independently of age and sample heterogeneity, and predicts progression to CIN3+ in HPV+ patients. RESULTS: The WID™-qCIN, assessing three regions in human genes DPP6, RALYL, and GSX1, was validated in both a diagnostic (case-control) and predictive setting (nested case-control), in a total of 761 samples. Using a predefined threshold, the sensitivity of the WID™-qCIN test was 100% and 78% to detect invasive cancer and CIN3, respectively. Sensitivity to detect CIN3+ was 65% and 83% for women < and ≥ 30 years of age. The specificity was 90%. Importantly, the WID™-qCIN test identified 52% of ≥ 30-year-old women with a cytology negative (cyt-) index sample who were diagnosed with CIN3 1-4 years after sample donation. CONCLUSION: We identified suitable DNAme regions in an epigenome-wide discovery using HPV+ controls and CIN3+ cases and established the WID™-qCIN, a PCR-based DNAme test. The WID™-qCIN test has a high sensitivity and specificity that may outperform conventional cervical triage tests and can in an objective, cheap, and scalable fashion identify most women with and at risk of (pre-)invasive cervical cancer. However, evaluation was limited to case-control settings and future studies will assess performance and generalisability in a randomised controlled trial.


Assuntos
Alphapapillomavirus , Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Adulto , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética , Detecção Precoce de Câncer , Metilação de DNA , Papillomaviridae/genética
5.
PLoS One ; 17(11): e0278117, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36417453

RESUMO

Sensitive and specific genotyping of human papillomaviruses (HPVs) is critical for the surveillance and monitoring of the vaccine effectiveness. Here, HPV genotypes were identified in 137 cervical samples with different histology (79 ≤CIN1 and 58 CIN3+) using Nested-PCR followed by Next-Generation sequencing (NGS) and relative proportions for each genotype in multiple infections were computed. All samples had been previously genotyped by PCR-Reverse Blotting Hybridization (PCR-RBH) thus allowing for a concordance analysis between both techniques. Multiple infections were present in 85% of ≤CIN1 cases compared to only 41% in CIN3+ cases (p<0.001). Among ≤CIN1 cases a towering genotypic diversity was observed, considering both low (LR-) and high risk (HR-) HPV genotypes; while among CIN3+, diversity was lower, HR-HPVs prevailing in most cases, especially HPV16. Furthermore, the predominance of HR-HPV genotypes in the proportions identified in each sample was higher in CIN3+ cases [(HPV16 (62.5%), followed by HPV31 and HPV58 (8.3% each)], than in ≤CIN1 cases [(HPV16 (17.7%), followed by HPV52 (14.7%) and HPV31 (10.3%)]. Agreement between PCR-RBH and NGS was higher than 90% for all genotypes (with an overall Kappa of 0.7), even though NGS identified eighty-nine positive results for HPV genotypes that had not been detected by PCR-RBH, evidencing its greater sensitivity. These results suggest that a reduction in genotypic diversity and/or an increase in the relative proportion of HR-HPVs in multiple infections can be considered as a biomarker for the potential risk of malignant progression.


Assuntos
Alphapapillomavirus , Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Papillomaviridae/genética , Alphapapillomavirus/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/epidemiologia , Genótipo , Neoplasia Intraepitelial Cervical/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias do Colo do Útero/patologia , Papillomavirus Humano 16/genética
6.
Ann Afr Med ; 21(4): 355-360, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36412334

RESUMO

Aims and Objectives: To compare the micronucleus (MN) score in all the major diagnostic categories as per "The Bethesda System for Reporting Cervical Cytology" 2014 including negative for intraepithelial lesions and malignancy (NILM), inflammatory, abnormal squamous cells of undetermined significance (ASC-US), abnormal squamous cells cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H), low-grade squamous intraepithelial lesion (LSIL), HSIL, and invasive carcinoma (IC) and to assess the role of MN scoring as a biomarker for predicting risk of carcinoma. Materials and Methods: A total of 1000 conventional cervical smears stained with Papanicolaou (Pap) stain, comprising unsatisfactory for evaluation (86), NILM (140), inflammatory (696), ASC-US (23), ASC-H (16), LSIL (18), HSIL (15), and IC (6) were studied independently by two pathologists, and the number of MN cells per 1000 epithelial cells in high-power (×400) and oil immersion (×1000) was counted and expressed as MN score per 1000 cells. Results: The mean MN score ± standard deviation was found to be 0.99 ± 0.744 in NILM cases, 0.67 ± 0.782 in inflammatory cases, 1.57 ± 0.507 in ASC-US cases, 1.63 ± 0.50 in ASC-H cases, 1.56 ± 0.511 in LSIL cases, 2.47 ± 0.516 in HSIL cases, and 3.0 ± 0.00 in IC cases. A step-wise increase was observed in MN score from inflammatory to IC categories. Conclusions: MN score is a reliable and easy test that can be used in conjunction with routine cervical PAP to assess the risk of malignant transformation in the uterine cervix as a biomarker for predicting the risk of carcinoma.


Résumé Objectifs et objectifs: comparer le score du micronucléus (MN) dans toutes les principales catégories de diagnostic selon "le système Bethesda pour signaler la cytologie cervicale" 2014, y compris négatif pour les lésions intraépithéliales et la malignité (Nilm), inflammatoire et anormal des cellules squameuses de signification indéterminées (Nilm), inflammatoire et anormale des cellules squameuses de signification indéterminées (Nilm), inflammatoire et anormale des cellules pure ASC - US), les cellules squameuses anormales ne peuvent pas exclure la lésion intraépithéliale épidermoïde de haute qualité (HSIL) (ASC - H), la lésion intraépithéliale squameuse à faible teneur (LSIL), le carcinome invasif (IC) et pour évaluer le rôle de MN La notation en tant que biomarqueur pour prédire le risque de carcinome. Matériaux et méthodes: un total de 1000 frottis cervicaux conventionnels colorés avec une tache de papanicolaou (PAP), comprenant insatisfaisant l'évaluation (86), nilm (140), inflammatoire (696), ASC - US (23), ASC - H (16), LSIL (18), HSIL (15) et IC (6) ont été étudiés indépendamment par deux pathologistes, et le nombre de cellules Mn pour 1000 cellules épithéliales dans la puissance (× 400) et l'immersion à l'huile (× 1000) ont été comptées et exprimé en score MN par 1000 cellules. Résultats: Le score MN moyen ± l'écart type s'est révélé être de 0,99 ± 0,744 dans des cas nilms, 0,67 ± 0,782 dans des cas inflammatoires, 1,57 ± 0,507 dans les cas ASC - US, 1,63 ± 0,50 dans les cas ASC - H, 1,56 ± 0,511 dans LSIL cas, 2,47 ± 0,516 dans les cas HSIL et 3,0 ± 0,00 dans les cas IC. Une augmentation de pas de pas a été observée dans le score MN des catégories inflammatoires vers IC. Conclusions: Le score MN est un test fiable et facile qui peut être utilisé en conjonction avec le PAP cervical de routine pour évaluer le risque de transformation maligne dans le col utérine en tant que biomarqueur pour prédire le risque de carcinome. Mots-clés: Frottis cervical, micronucleus, dépistage.


Assuntos
Carcinoma de Células Escamosas , Neoplasia Intraepitelial Cervical , Neoplasias do Colo do Útero , Feminino , Humanos , Esfregaço Vaginal , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Teste de Papanicolaou , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia
7.
J Cancer Res Ther ; 18(6): 1485-1489, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36412398

RESUMO

Introduction: Cervical cancer is one of the leading causes of cancer deaths among women. It results due to human papillomavirus (HPV) infection. Cervical intraepithelial neoplasia (CIN) is the preinvasive condition of cervical cancer. Various objective immunohistochemical (IHC) markers have been studied for cervical cancer. This study is aimed at studying the expression of B-cell lymphoma-2 (Bcl-2) IHC marker among preinvasive and invasive lesions of cervical cancer and its association with HPV infection. Methodology: This prospective study was conducted over a period of 1 year in a tertiary care hospital in central India, included 73 women suffering from CIN and cancer cervix. The expression of Bcl-2 and the presence of HPV genotypes were studied. Results: Out of 73 patients, 34 had cancer cervix, out of which 15 (44%) had Bcl-2 positivity, 24 had CIN 1, out of which 13 (54%) had Bcl-2 positivity, 10 had CIN 2, out of which 4 (40%) had Bcl-2 positivity and 5 had CIN 3, out of which 3 (60%) had Bcl-2 positivity. No significant difference was found in Bcl-2 positivity among CIN-1, CIN-2, CIN-3, and cancer cervix cases with a Chi-square value of 1.116 and P = 0.77. HPV positivity was found in 41 (56%) out of 73 patients where HPV 16 subtype was the most common (31.5%), followed by HPV 18 (13.7%). No significant association between HPV positivity and Bcl-2 positivity was found with P = 0.34. Conclusion: Bcl-2 IHC seems to have variable expression among CIN cases. Although its expression is low among invasive cancer cases when compared with preinvasive lesions, the difference is not significant. Similarly, no significant association was found between Bcl-2 expression and HPV infections.


Assuntos
Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Estudos Prospectivos , Neoplasia Intraepitelial Cervical/patologia , Papillomaviridae/genética , Biomarcadores , Proteínas Proto-Oncogênicas c-bcl-2/genética
8.
J Cancer Res Ther ; 18(6): 1541-1547, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36412407

RESUMO

Introduction: The aim of this study was to compare overtreatment rates of see and treat colposcopy-based single step protocol with cytology and colposcopy-guided biopsy-based conventional three-step protocol using loop electrosurgical excision procedure (LEEP) for treatment of preinvasive lesions of cervix. Materials and Methods: Prospective interventional study was carried out over a period of 1 year. Recruitment of cases was done from the 664 diagnostic colposcopies performed for various gynecological indications. Among 496 colposcopies performed exclusively for unhealthy cervix on per speculum examination, 74 women had high-grade colposcopy (Swede score ≥5). Subsequently, 50 women were enrolled under the see and treat arm, arm 1 and underwent LEEP. In study arm 2, conventional three-step strategy, concurrently 22 women with abnormal cytology. ≥ Atypical squamous cells of undetermined significance and unhealthy cervix were enrolled for colposcopy and if indicated, guided biopsy was obtained and tissue was sent for histopathology. Only 12 such women having HPE reports of cervical intraepithelial neoplasia (CIN) 2 or 3 were subjected to LEEP. Overtreatment was defined as CIN 1 or less on final LEEP tissue histopathology. Results: The overtreatment rate in See and Treat protocol was 44% when colposcopy Swede score cutoff was considered 5, which fell down to 0% when Swede score cutoff was taken 7. Conventional three step protocol had an overtreatment rate of 8.3%. Incidentally diagnosed high-grade CIN or invasive cancer was found in 24%. Discrepancy between biopsy tissue and LEEP tissue histopathology was 50% in conventional arm. Conclusion: Women with unhealthy cervix having high-grade colposcopy (Swede score ≥7) can be directly subjected to LEEP without waiting for results of any initial screening modality. Advantages include minimal over treatment coupled with reduced patient visits and interventions.


Assuntos
Neoplasia Intraepitelial Cervical , Neoplasias do Colo do Útero , Feminino , Humanos , Gravidez , Eletrocirurgia/métodos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Estudos Prospectivos , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/cirurgia , Neoplasia Intraepitelial Cervical/patologia , Colposcopia
9.
J Cancer Res Ther ; 18(6): 1564-1568, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36412411

RESUMO

Objective: The objective of the study was to determine the reasons for improper simple hysterectomy in the presence of invasive cervical cancer in Northeast India. Materials and Methods: The medical records of 52 patients who had undergone improper simple hysterectomy in the presence of invasive cervical cancer and were referred to a tertiary regional cancer Institute at Guwahati, Assam, between January 2015 and December 2019 were reviewed. Results: Most of the patients presented with abnormal vaginal bleeding (40.4%). The failure to perform cervical cytology before the operation was quite high at 48.1% (25 patients). Interestingly, normal cytologic smear could still be found in 15.4% (8 patients) despite the presence of invasive cervical cancer. Failure to perform preoperative Papanicolaou smear, incomplete evaluation of cervical intraepithelial neoplasia (CIN) on cervical biopsy, and negative Papanicolaou smear accounted for 75% of the patients undergoing inappropriate simple hysterectomy. The most common indications for inappropriate operation were abnormal vaginal bleeding (40.4%) and CIN (19.2%). The reasons for inappropriate simple hysterectomy included lack of preoperative cervical cytology (48.1%), false-negative cervical cytology (15.4%), incomplete evaluation of cervical dysplasia or microinvasion on biopsy (11.5%). failure to perform indicated conization( 5.8%), emergency hysterectomy (3.8%), errors in colposcopic examination (3.8%), incomplete evaluation of an abnormal cervical cytology (3.8%), failure to review slide (3.8%) and failure to biopsy a gross cervica lesion (3.8%). Conclusion: Most improper simple hysterectomy resulted from deviation from guideline for cervical cancer detection protocols. Improper simple hysterectomy in the presence of invasive cervical cancer can be avoided if one sticks to the diagnostic guideline for patients with an abnormal cervical cytology.


Assuntos
Neoplasia Intraepitelial Cervical , Neoplasias do Colo do Útero , Gravidez , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/cirurgia , Colposcopia , Estudos Retrospectivos , Histerectomia/métodos , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/cirurgia , Teste de Papanicolaou , Hemorragia Uterina
10.
BMC Med ; 20(1): 437, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352434

RESUMO

BACKGROUND: Cervical squamous cell carcinoma (SCC) is known to arise through increasingly higher-grade squamous intraepithelial lesions (SILs) or cervical intraepithelial neoplasias (CINs). This study aimed to describe sequential molecular changes and identify biomarkers in cervical malignant transformation. METHODS: Multidimensional data from five publicly available microarray and TCGA-CESC datasets were analyzed. Immunohistochemistry was carried out on 354 cervical tissues (42 normal, 62 CIN1, 26 CIN2, 47 CIN3, and 177 SCC) to determine the potential diagnostic and prognostic value of identified biomarkers. RESULTS: We demonstrated that normal epithelium and SILs presented higher molecular homogeneity than SCC. Genes in the region (e.g., 3q, 12q13) with copy number alteration or HPV integration were more likely to lose or gain expression. The IL-17 signaling pathway was enriched throughout disease progression with downregulation of IL17C and decreased Th17 cells at late stage. Furthermore, we identified AURKA, TOP2A, RFC4, and CEP55 as potential causative genes gradually upregulated during the normal-SILs-SCC transition. For detecting high-grade SIL (HSIL), TOP2A and RFC4 showed balanced sensitivity (both 88.2%) and specificity (87.1 and 90.1%), with high AUC (0.88 and 0.89). They had equivalent diagnostic performance alone to the combination of p16INK4a and Ki-67. Meanwhile, increased expression of RFC4 significantly and independently predicted favorable outcomes in multi-institutional cohorts of SCC patients. CONCLUSIONS: Our comprehensive study of gene expression profiling has identified dysregulated genes and biological processes during cervical carcinogenesis. RFC4 is proposed as a novel surrogate biomarker for determining HSIL and HSIL+, and an independent prognostic biomarker for SCC.


Assuntos
Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Prognóstico , Biomarcadores Tumorais/metabolismo , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/patologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Expressão Gênica , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética , Proteína de Replicação C/genética , Proteína de Replicação C/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
11.
Front Public Health ; 10: 1010066, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438219

RESUMO

Objective: To validate the HPV viral loads that are reflected by the cycle threshold values of Cobas4800 as the viral load indicators by verifying the consistency of the viral loads per unit (10,000 cells) from the BMRT assay. Methods: The analysis is based on data from the Chinese Multi-Center Screening Trial (CHIMUST). The cases included in the analysis are all positive for physician-collected hrHPV on SeqHPV and/or Cobas4800 or negative for hrHPV but abnormal in cytology (≥LSIL), and some cases selected by nested case-control randomization from those negative for physician-collected hrHPV and cytology. With HPV testing results and relevant Ct values from Cobas4800 available, we tested the entire sample set with the BMRT HPV testing assay and analyzed their agreement with Cobas4800, followed by a comparison of the CtV from Cobas4800 and viral loads (lg) from BMRT by lesion grade. Results: We included 4,485 women (mean age: 45.4 years) in the study, and 4,290 had complete data. The consistency of genotypes from Cobas4800 and BMRT for hrHPV, HPV-16, HPV-18, and 12-HPV pools was 94.9% (4070/4290, Kappa = 0.827), 99.1% (4251/4290, Kappa = 0.842), 99.6% (4,273/4,290, Kappa = 0.777), and 95.3% (4,089/4,290, Kappa = 0.821), respectively. Further analysis shows that any inconsistency between the two assays is likely among samples with comparatively lower viral loads. When analyzing per lesions of CIN2+ and CIN3+, the CtV from Cobas4800 and VL (lg) from BMRT are highly correlated inversely and follow the linear regression for HPV16 and 12-HPV pool (Pearson's or Spearman's correlation coefficient (r): In CIN3+, r HPV16 = -0.641, P < 0.001; r 12-HPVpool = -0.343, P = 0.109; In CIN2+, r HPV16 = -0.754, P < 0.001; r 12-HPVpool = -0.429, P < 0.001). Conclusion: The CtV from Cobas4800 and the viral loads (lg) of per unit cells from the BMRT are well correlated for lesion grading when tested on physician-collected samples. Cobas-CtV is worthy of further study for clinical application.


Assuntos
Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Detecção Precoce de Câncer/métodos , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Infecções por Papillomavirus/diagnóstico , Carga Viral
12.
Artigo em Inglês | MEDLINE | ID: mdl-36429432

RESUMO

Human papillomavirus type 16 (HPV16) and/or high-risk (Hr-) HPV are the main causes of cervical cancer. Another element that may contribute to the development of cervical cancer is the microbiota. To date, no study has investigated the entire cervical microbiome, which consists of bacteria, fungi, and viruses. In this study, cervical samples with different histopathology (CIN1, CIN2, and CIN3), with or without HPV16 and Hr-HPVs infection, were enrolled. From bacterial community analysis, 115 bacterial species were found and separated into 2 distinct categories based on Lactobacillus abundance: Lactobacilli-dominated (LD) and non-Lactobacilli-dominated (NLD) groups. The LD group had significantly less bacterial diversity than the NLD group. In addition, the variety of bacteria was contingent on the prevalence of HPV infection. Among distinct histological groups, an abundance of L. iners (>60% of total Lactobacillus spp.) was discovered in both groups. A few fungi, e.g., C. albicans, were identified in the fungal community. The viral community analysis revealed that the presence of HPV considerably reduced the diversity of human viruses. Taken together, when we analyzed all our results collectively, we discovered that HPV infection was a significant determinant in the diversity of bacteria and human viruses in the cervix.


Assuntos
Neoplasia Intraepitelial Cervical , Microbiota , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Infecções por Papillomavirus/epidemiologia , Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Neoplasia Intraepitelial Cervical/epidemiologia , Papillomavirus Humano 16 , Lactobacillus
13.
Medicina (Kaunas) ; 58(11)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36422194

RESUMO

Background and Objectives: Cervical squamous cell carcinoma (SCC) usually showed an infiltrative growth pattern into endocervical stroma. In rare cases, SCC spreads superficially as an intraepithelial lesion to proximal uterine segments, and more rarely, involves invasive and more aggressive behavior on secondary sites. Materials and Methods: In this study, we present the case of an interesting form of cervical SCC growth and we discuss the possible reasons for that presentation. Results: After clinical examination and repeated histomorphological analysis, we found remarkable cervical epithelial dysplasia (a high-grade squamous intraepithelial lesion-H-SIL). A histopathology report after conization and hysterectomy showed squamocellular carcinoma with microinvasive focuses. Interestingly, squamocellular carcinoma was found in the proximal uterine and adnexal structure, as well as intraepithelial and microinvasive lesions. Conclusions: Our study described a rare presentation of primary cervical SCC with unusual adnexal involvement. This pattern of tumor growth should be especially considered for patients who are proposed for sparing surgical procedures. A detailed and multidisciplinary approach for every patient is very important because unpredictable cases are present. However, they are rare.


Assuntos
Neoplasias da Mama , Carcinoma de Células Escamosas , Neoplasia Intraepitelial Cervical , Neoplasias de Tecido Conjuntivo , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/cirurgia , Carcinoma de Células Escamosas/cirurgia , Histerectomia
14.
Medicine (Baltimore) ; 101(43): e31368, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36316892

RESUMO

Postmenopausal women have a high risk for pathological upgrading in conization specimens due to pathological changes of the cervix. This study aimed to investigate the risk factors for pathological upgrading in conization specimens in Chinese women with cervical intraepithelial neoplasia grade 2/3 (Cervical intraepithelial neoplasia 2/3) ≥ 50 years of age. From January 2015 to December 2019, 443 CIN2/3 patients ≥ 50 years of age were retrospectively included and divided into the upgrade group (n = 47) and the non-upgrade group (n = 396) according to the presence or absence of pathological upgrading in the conization specimens. Multivariate logistic regression model was performed to analyze risk factors associated with pathological upgrading. The upgrade group was more likely to have gravidity < 2 times, postmenopausal period ≥ 5 years, higher incidences of endocervical glandular involvement (EGI) and human papillomavirus (HPV) 16/18 infection, as well as a lower incidence of cervical contactive bleeding and fewer cases undergoing endocervical curettage (all P < .05) than the non-upgrade group. Multivariate model showed that factors associated with pathological upgrading were postmenopausal period ≥ 5 years (OR = 2.55), EGI (OR = 17.71), endocervical curettage (OR = 0.33), and HPV type 16/18 (OR = 3.41) (all P < .05). The receiver operating characteristic analysis showed an area under curve of 0.782 (P < .001). Pathological upgrading in conization specimens is not uncommon in Chinese CIN2/3 patients ≥ 50 years of age. For those with high-risk factors of pathological upgrading (postmenopausal period ≥ 5 years, EGI, and HPV 16/18 infection), the follow-up interval can be appropriately shortened, and active intervention could be considered.


Assuntos
Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasia Intraepitelial Cervical/patologia , Conização , Papillomavirus Humano 16 , Estudos Retrospectivos , Perimenopausa , Neoplasias do Colo do Útero/patologia , Papillomavirus Humano 18 , Papillomaviridae , Fatores de Risco
15.
J Reprod Immunol ; 154: 103763, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36399874

RESUMO

COVID-19 is a multisystem disease and cause of a global pandemic. Lately, cases of disease progression of HPV-infected CIN under SARS-CoV-2 infection were reported giving rise to the hypothesis of direct virus-infection induced pro-carcinogenic effect of SARS-CoV-2. We herein present a case of rapid progression from HPV-induced CIN 2 to microinvasive carcinoma within three months under COVID-19 without direct virus infection. Histopathologic evaluation, Fluorescence-in-situ hybridization and qRT-PCR against SARS-CoV-2 RNA as well as gene expression analysis were performed from the available FFPE-tissue and accompanied by an analysis of white blood cell differential. No signs of direct SARS-CoV-2 infection or COVID-19 typical alterations of cervical tissue were found. As expected, p53 decreased in expression with progression of dysplasia, while APOBEC3A and VISTA showed a decrease in expression contrary to observations in dysplasia progression. PD-L1 was expressed consistently or increased slightly but did not show the expected strong induction of expression. DNMT1 showed an increase in expression in CIN III and a slight decrease in carcinoma, while DNMT3a is consistently expressed in CIN II and decreased in carcinoma. Blood tests after COVID-19 showed substantial reduction of lymphocytes, eosinophils, T-cells, and NK-cells. Our results hint at an indirect effect of COVID-19 on the cervical neoplasm. We conclude that the immune system might be preoccupied and exhausted by the concurring COVID-19 disease, leading to less immunological pressure on the HPV-infected cervical dysplasia enabling rapid disease progression. Further, indirect proangiogenic and proinflammatory micromilieu due to the multisystemic effects of COVID-19 might play an additional role.


Assuntos
COVID-19 , Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Feminino , Humanos , SARS-CoV-2 , Infecções por Papillomavirus/complicações , RNA Viral , Leucócitos , Progressão da Doença
16.
Zhonghua Liu Xing Bing Xue Za Zhi ; 43(11): 1821-1827, 2022 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-36444468

RESUMO

Objective: To investigate the correlation between methylation in human papillomavirus 16 (HPV16) long control region (LCR) and cervical intraepithelial neoplasia grade ≥2 (CIN2+). Methods: The literature retrieval was conducted by using the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang data and Weipu according to the inclusion and exclusion criteria, and the retrieval period was from the establishment of the databases to February 27th, 2022. Software RevMan 5.3 and Stata 15.1 were used for Meta-analysis. Results: A total of 17 literatures were included involving 1 421 subjects. Results of Meta-analysis showed that OR of the correlation between methylation of HPV16 LCR and CIN2+ was 1.56 (95%CI: 0.70-3.47). Subgroup analysis showed that methylation of the 5' terminal, enhancer and promoter regions were not associated with CIN2+, while in four E2 binding sites (E2BS), the methylation of E2BS1, E2BS3 and E2BS4 increased the risk of CIN2+, with the ORs of 3.92 (95%CI: 1.92-7.99), 10.50 (95%CI: 3.67-30.04) and 3.65 (95%CI: 1.58-8.41), respectively. However, subgroup analysis on E2BS2 was not performed due to the limitation of the number of literatures. According to the different sources of population, the risk of CIN2+ in Chinese population was associated with methylation of HPV16 LCR (OR=2.14, 95%CI: 1.31-3.50). There was a correlation between the risk of CIN2+ and HPV16 LCR methylation in the population with pyrosequencing of HPV16 LCR, and OR was 1.75 (95%CI: 1.03-2.98). Conclusion: The risk of CIN2+ is correlated with the methylation of E2BS in HPV16 LCR, which can be used as potential biomarkers.


Assuntos
Neoplasia Intraepitelial Cervical , Neoplasias do Colo do Útero , Feminino , Humanos , Metilação , Papillomavirus Humano 16/genética , Asiáticos
17.
Virol J ; 19(1): 177, 2022 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335385

RESUMO

BACKGROUND: Human papilloma virus (HPV) DNA test was applied in cervical cancer screening as an effective cancer prevention strategy. The viral load of HPV generated by different assays attracted increasing attention on its potential value in disease diagnosis and progression discovery. METHODS: In this study, three HPV testing datasets were assessed and compared, including Hybrid Capture 2 (n = 31,954), Aptima HPV E6E7 (n = 3269) and HPV Cobas 4800 (n = 13,342). Logistic regression models for diagnosing early cervical lesions of the three datasets were established and compared. The best variable factor combination (VL + BV) and dataset (HC2) were used for the establishment of six machine learning models. Models were evaluated and compared, and the best-performed model was validated. RESULTS: Our results show that viral load value was significantly correlated with cervical lesion stages in all three data sets. Viral Load and Bacterial Vaginosis were the best variable factor combination for logistic regression model establishment, and models based on the HC2 dataset performed best compared with the other two datasets. Machine learning method Xgboost generated the highest AUC value of models, which were 0.915, 0.9529, 0.9557, 0.9614 for diagnosing ASCUS higher, ASC-H higher, LSIL higher, and HSIL higher staged cervical lesions, indicating the acceptable accuracy of the selected diagnostic model. CONCLUSIONS: Our study demonstrates that HPV viral load and BV status were significantly associated with the early stages of cervical lesions. The best-performed models can serve as a useful tool to help diagnose cervical lesions early.


Assuntos
Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Lesões Pré-Cancerosas , Neoplasias do Colo do Útero , Feminino , Humanos , Detecção Precoce de Câncer/métodos , Infecções por Papillomavirus/diagnóstico , Papillomaviridae/genética , Lesões Pré-Cancerosas/diagnóstico , DNA Viral/genética
18.
BMC Cancer ; 22(1): 1052, 2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36207693

RESUMO

BACKGROUND: Cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer which is the major cause of death in women worldwide. Although squamous cell carcinoma antigen (SCC-Ag) is widely used to detect CESC, it is not sensitive and specific enough to predict the disease. METHODS: We investigated serum CXC motif chemokine 10 (CXCL10) as potential diagnostic biomarker in detecting CESC in this study. Serum levels of CXCL10 and SCC-Ag were measured by ELISA or automated immunoassay in 345 participants, including 189 patients with different stages of CESC, 75 patients with cervical intraepithelial neoplasia, and 81 healthy individuals. Performances of CXCL10 and SCC-Ag as single biomarkers were analyzed by the ROC curves. The changes of serum levels of CXCL10 and SCC-Ag in 10 longitudinal followed-up CESC patients with partial response (PR) during chemoradiotherapy or chemotherapy were evaluated. RESULTS: The two markers showed similar diagnostic capacity in distinguishing both CESC early stage from healthy controls (AUCCXCL10 = 0.740, AUCSCC-Ag = 0.710) and all CESC from healthy controls (AUCCXCL10 = 0.775, AUCSCC-Ag =0.793). Moreover, CXCL10 showed ability in distinguishing cervical intraepithelial neoplasia from healthy control (AUCCXCL10 = 0.727) and cervical cancer SCC-Ag-negative from healthy control. (AUCCXCL10 = 0.739). The combination of CXCL10 and SCC-Ag displayed significant improvement of AUCs than individual SCC-Ag or CXCL10 in the analysis groups (healthy vs all cervical cancer, healthy vs cervical cancer early stage). The AUCs were improved to 0.877 (AUCSCC-Ag = 0.793, P < 0.05) to distinguish healthy controls from all CESC and 0.828(AUCSCC-Ag = 0.710, P < 0.05) to distinguish healthy controls from CESC early stage by the combination of the two markers, respectively. Significant differences of serum CXCL10 levels were found between CESC patients at late tumor stage and CESC patients at early tumor stage (P < 0.01). Serum CXCL10 levels of the CESC patients who had partial response after treatment significantly decreased during treatment (P = 0.013), whose consistent and inconsistent frequency with the response were the same as serum SCC-Ag levels. CONCLUSIONS: The results indicated that CXCL10 is a potential serum biomarker complementing SCC-Ag in prediction of CESC. CXCL10 showed ability in the diagnosis of SCC-Ag negative CESC and the combination of CXCL10 and SCC-Ag inhibited improved performance compared with SCC-Ag alone.


Assuntos
Neoplasias da Mama , Carcinoma de Células Escamosas , Neoplasia Intraepitelial Cervical , Serpinas , Neoplasias do Colo do Útero , Antígenos de Neoplasias , Biomarcadores Tumorais , Carcinoma de Células Escamosas/patologia , Quimiocina CXCL10 , Quimiocinas , Feminino , Humanos , Prognóstico , Neoplasias do Colo do Útero/patologia
19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(5): 896-903, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36224694

RESUMO

Objective: To evaluate the clinical value of different combination strategies of high-risk HPV (hr-HPV) testing and Thinprep cytology test (TCT), a cervical cytology test, for cervical cancer screening, especially for high or higher-grade squamous intraepithelial lesion (HSIL+) in Shuangliu District, Chengdu City. Methods: The study is a population-based randomized clinical trial. Women aged 35 to 65 years meeting the inclusion criteria were enrolled for the study. At the baseline screening conducted in the first year, the participants were randomly assigned to either cytology test or hr-HPV testing at a ratio of 1∶2. If the paticipants had positive results for the baseline hr-HPV test, they would then undergo either cytology test or colposcopy by random assignment. After 24 months, all participants were called back, and combined screening of cytology test and hr-HPV test were performed. Women who had negative results at baseline screening and who entered and completed the third-year follow-up were selected as the subjects of the study. Based on the aforementioned testing findings, the related data were extracted and four different screening protocols were simulated: 1) combined TCT and hr-HPV screening, with referral for colposcopy when there was positive results for either one of the two; 2) combined TCT and hr-HPV screening, with referral for colposcopy when both tests had positive results at the same time; 3) TCT was done for preliminary screening and those who were found to be positive would then undergo hr-HPV test for triage purpose, with subsequent referral made for colposcopy if the hr-HPV results were positive; 4) hr-HPV was done for preliminary screening and those who were found to be positive would then undergo TCT, with subsequent referral made for colposcopy if TCT results were positive. With the detection of HSIL+ on histological examination as the endpoint event, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve ( AUC) of different combination screening models were calculated. Results: A total of 3102 women were screened, and 2967 women were included in the statistical analysis in this study. Among the 2967 women, 979 were randomized to cytology and 1988 to hr-HPV genotyping. For prescreening, the positive rate of the cytology group was 5.6% (55/979), with of HSIL+ positive rate being 0.2% (2/979), while the positive rate of the hr-HPV group was 7.5% (149/1988), with HSIL+ positive rate being 0.9% (18/1988). After 24 months, 2456 women were called back and were given cervical cytology test and hr-HPV test at the same time. Among them, the positive rate of the cytology group was 3.2% (78/2456), while the positive rate of hr-HPV group was 8.7% (215/2456). The overall positive rate of HSIL+ was 0.69%(17/2456). Women with a negative baseline hr-HPV had a lower incidence of HSIL+ lesions in the long term. The strategy of cervical cytology screening combined with hr-HPV test for triage purpose is the best method, with a sensitivity of 88.9%, a specificity of 58.3%, a PPV of 44.4%, a NPV of 93.3%, and an AUC of 0.736, P=0.039 (95% CI: 0.555-0.917). Conclusion: This randomized clinical trial from Shuangliu District, Chengdu City shows that the sensitivity of hr-HPV testing is better than that of cytology test, and the prevalence of HSIL+ in women with negative baseline hr-HPV results is lower than that of women with negative baseline cytology results. The screening program of TCT for prescreening plus subsequent hr-HPV test for triage purpose shows better value for the detection of HSIL+.


Assuntos
Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Neoplasia Intraepitelial Cervical/patologia , Colposcopia/efeitos adversos , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Programas de Rastreamento/efeitos adversos , Programas de Rastreamento/métodos , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Gravidez , Neoplasias do Colo do Útero/patologia
20.
Int J Hyperthermia ; 39(1): 1294-1299, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36191925

RESUMO

PURPOSE: To compare the efficacy and safety of focused ultrasound (FUS) therapy and cryotherapy for cervical squamous intraepithelial lesion (SIL). METHODS: In this retrospective study, data pertaining to women treated for cervical SIL with FUS therapy or cryotherapy at the Second Affiliated Hospital of Chongqing Medical University between 21 April 2018 and 31 August 2020 were obtained. The patients were followed up after 3-6 and 6-12 months. The proportions of women with no evidence of disease, recurrent disease, clearance of the human papillomavirus (HPV) and adverse effects or complications were determined. RESULTS: Of the 250 women with complete data who were included in the study, 144 and 106 received FUS therapy and cryotherapy, respectively. Overall, FUS therapy was observed to be more effective than cryotherapy (91.7 vs. 79.2%, p = 0.005). Statistically significant differences were noted in the treatment efficacy for patients with low-grade SIL (LSIL) (92.3 vs. 80.2%, p = 0.011). However, there were no significant differences in the treatment efficacy for patients with high-grade SIL (HSIL) (88.9 vs. 75.0%, p = 0.390). The recurrence rates in patients with LSIL treated with FUS therapy or cryotherapy showed no significant differences at the 6-12-month follow-up (1.0 vs. 6.0%, p = 0.163). Furthermore, there was no recurrence in patients with HSIL, either in the FUS or cryotherapy group. FUS therapy and cryotherapy resulted in similar HPV clearance at the 3-6-month follow-up (77.1 vs. 64.8%, p = 0.057). No statistically significant differences were observed in the complication rates between the two groups (3.5 vs. 1.9%, p = 0.717). CONCLUSION: The results of this study suggest that FUS therapy is superior to cryotherapy in the treatment of cervical LSIL.


Assuntos
Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Lesões Intraepiteliais Escamosas , Neoplasias do Colo do Útero , Neoplasia Intraepitelial Cervical/diagnóstico por imagem , Neoplasia Intraepitelial Cervical/terapia , Crioterapia , Feminino , Humanos , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/terapia , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
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