RESUMEN

Objective: To describe Top-hat results and their association with margin status and disease relapse in a referral facility in Brazil. Methods: A retrospective study of 440 women submitted to LEEP to treat HSIL, in which 80 cases were complemented immediately by the top hat procedure (Top-hat Group - TH). TH Group was compared to women not submitted to Top-hat (NTH). The sample by convenience included all women that underwent LEEP from January 2017 to July 2020. The main outcome was the histological result. Other variables were margins, age, transformation zone (TZ), depth, and relapse. The analysis used the Chi-square test and logistic regression. Results: The TH Group was predominantly 40 and older (NTH 23.1% vs. TH 65.0%, p<0.001). No difference was found in having CIN2/CIN3 as the final diagnosis (NTH 17.0% vs. TH 21.3%, p=0.362), or in the prevalence of relapse (NTH 12.0% vs. TH 9.0%, p=0.482). Of the 80 patients submitted to top hat, the histological result was CIN2/CIN3 in eight. A negative top hat result was related to a negative endocervical margin of 83.3%. A CIN2/CIN3 Top-hat result was related to CIN2/CIN3 margin in 62.5% (p=0.009). The chance of obtaining a top hat negative result was 22.4 times higher (2.4-211.0) when the endocervical margin was negative and 14.5 times higher (1.5-140.7) when the ectocervical margin was negative. Conclusion: The top hat procedure did not alter the final diagnosis of LEEP. No impact on relapse was observed. The procedure should be avoided in women of reproductive age.

Asunto(s)

Neoplasias del Cuello Uterino , Humanos , Femenino , Estudios Retrospectivos , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Brasil , Displasia del Cuello del Útero/cirugía , Displasia del Cuello del Útero/diagnóstico , Detección Precoz del Cáncer , Márgenes de Escisión

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OBJECTIVE: This systematic review and meta-analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites. MATERIALS AND METHODS: A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered. RESULTS: Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59-1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09-1.09]) for recurrence was observed when cold-knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN. CONCLUSION: There is no difference in recurrence risk post-surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches.

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PURPOSE: Emerging evidence suggests that vaginal micro-environment disorder is closely related to the development of cervical lesions. Low-grade cervical intraepithelial neoplasia (CIN1), as an early stage of cervical lesions, exhibits a high risk of progressing to high-grade lesions or even cervical cancer. However, the effect of vaginal micro-environment on the malignant prognosis of CIN1 remains uncertain. METHODS: A total of 504 patients diagnosed with CIN1 by pathology, who were from the population-based cohorts established in Shanxi Province, China, were enrolled and followed up for 2 years. Micro-environmental factors such as vaginal pH, cleanliness, hydrogen peroxide (H2O2), ß-glucuronidase (GUSB), leucocyte esterase (LE), and sialidase (SNA) were detected to evaluate their effect on the malignant prognosis of CIN1. RESULTS: Abnormal vaginal pH (HR = 1.472, 95%CI 1.071-2.022), cleanliness (HR = 1.446, 95%CI 1.067-1.960), H2O2 (HR = 1.525, 95%CI 1.155-2.013), GUSB (HR = 1.739, 95%CI 1.235-2.448), LE (HR = 1.434, 95%CI 1.038-1.981), and SNA (HR = 1.411, 95%CI 1.065-1.870) could promote a higher incidence of CIN1 malignant prognosis, and the combined effects of these micro-environmental factors resulted in a nearly twofold increased risk (HR = 2.492, 95%CI 1.773-3.504) compared to any single factor alone, especially under the high-risk human papillomavirus (HR-HPV) infection. Notably, the cumulative incidence of malignant prognosis for CIN1 gradually increased during the early follow-up period, reaching its peak at approximately 8 months, and then stabilizing. CONCLUSION: Vaginal micro-environment disorder could promote CIN1 malignant prognosis, particularly in HR-HPV-infected women. Taking micro-environmental factors as the breakthrough, our study provides a feasible vision for preventing early stage cervical lesions.

Asunto(s)

Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Vagina , Humanos , Femenino , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/virología , China/epidemiología , Pronóstico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Adulto , Estudios Prospectivos , Persona de Mediana Edad , Vagina/patología , Concentración de Iones de Hidrógeno , Peróxido de Hidrógeno , Microambiente Tumoral , Glucuronidasa/metabolismo , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Estudios de Seguimiento , Adulto Joven

RESUMEN

OBJECTIVE: To compare the sensitivity and specificity of DNA ploidy with cytology, human papillomavirus (HPV) testing and colposcopy in diagnosis of high-grade cervical intraepithelial neoplasia (CIN) and to assess the role of aneuploidy in cervical lesions with the worst prognosis. A prospective observational cohort study was conducted on 254 women with altered colpocytology. METHODS: Colposcopy, biopsy, DNA-ICM and HPV examinations were applied to cervical cytological and histological samples. Participants were evaluated every 6 months and divided into two groups: 'Harm' and 'No-harm'. Logistic regression and multivariate COX model were used to identify independent risk factors for diagnosis and prognosis of high-grade CIN, and ROC curve to assess the sensitivity and specificity of methods. RESULTS: Variables 'age greater than or equal to 30 years', 'lesion size greater than 20%', 'aneuploidy' and 'HPV 16' were associated with diagnosis of high-grade CIN and 'aneuploidy' and 'women living with HIV', with a worse prognosis. Agreement for colposcopy was good, with a sensitivity of 79.3% and specificity of 94.4%; DNA-ICM and cytology were moderate, with sensitivity of 74.6% and 72.3% and specificity of 85.3% and 76.1%, respectively. High-risk HPV and HPV 16 tests were weak, with sensitivity of 75.0% and 43.75% and specificity of 50.0% and 88.64%, respectively. CONCLUSIONS: In relation to high-grade CIN diagnosis, DNA-ICM presented similar sensitivity and specificity to cytology and high-risk HPV test when associated with HPV 16. Regarding prognosis, this research certifies that aneuploidy is considered a predictor of more severe cervical injury.

Asunto(s)

Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Embarazo , Femenino , Humanos , Estudios Prospectivos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/complicaciones , Papillomaviridae/genética , Displasia del Cuello del Útero/patología , Sensibilidad y Especificidad , Colposcopía , Aneuploidia , Papillomavirus Humano 16/genética , ADN , ADN Viral/genética , Frotis Vaginal/métodos

RESUMEN

ABSTRACT BACKGROUND: Managing cervical intraepithelial neoplasia grade 2 (CIN2) is challenging, considering the CIN2 regression rate, perinatal risks associated with excisional procedures, and insufficient well-established risk factors to predict progression. OBJECTIVES: To determine the ability of p16INK4a and Ki-67 staining in biopsies diagnosed with CIN2 to identify patients with higher-grade lesions (CIN3 or carcinoma). DESIGN AND SETTING: Cross-sectional study conducted at a referral center for treating uterine cervical lesions. METHODS: In 79 women, we analyzed the correlation of p16INK4a and Ki-67 expression in CIN2 biopsies with the presence of a higher-grade lesions, as determined via histopathology in surgical specimens from treated women or via two colposcopies and two cytological tests during follow-up for untreated women with at least a 6-month interval. The expression of these two biomarkers was verified by at least two independent pathologists and quantified using digital algorithms. RESULTS: Thirteen (16.8%) women with CIN2 biopsy exhibited higher-grade lesions on the surgical excision specimen or during follow-up. p16INK4a expression positively and negatively predicted the presence of higher-grade lesions in 17.19% and 86.67% patients, respectively. Ki-67 expression positively and negatively predicted the presence of higher-grade lesions in 40% and 88.24% patients, respectively. CONCLUSIONS: Negative p16INK4a and Ki67 immunohistochemical staining can assure absence of a higher-grade lesion in more than 85% of patients with CIN2 biopsies and can be used to prevent overtreatment of these patients. Positive IHC staining for p16INK4a and Ki-67 did not predict CIN3 in patients with CIN2 biopsies.

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Abstract Objective: To describe Top-hat results and their association with margin status and disease relapse in a referral facility in Brazil. Methods: A retrospective study of 440 women submitted to LEEP to treat HSIL, in which 80 cases were complemented immediately by the top hat procedure (Top-hat Group - TH). TH Group was compared to women not submitted to Top-hat (NTH). The sample by convenience included all women that underwent LEEP from January 2017 to July 2020. The main outcome was the histological result. Other variables were margins, age, transformation zone (TZ), depth, and relapse. The analysis used the Chi-square test and logistic regression. Results: The TH Group was predominantly 40 and older (NTH 23.1% vs. TH 65.0%, p<0.001). No difference was found in having CIN2/CIN3 as the final diagnosis (NTH 17.0% vs. TH 21.3%, p=0.362), or in the prevalence of relapse (NTH 12.0% vs. TH 9.0%, p=0.482). Of the 80 patients submitted to top hat, the histological result was CIN2/CIN3 in eight. A negative top hat result was related to a negative endocervical margin of 83.3%. A CIN2/CIN3 Top-hat result was related to CIN2/CIN3 margin in 62.5% (p=0.009). The chance of obtaining a top hat negative result was 22.4 times higher (2.4-211.0) when the endocervical margin was negative and 14.5 times higher (1.5-140.7) when the ectocervical margin was negative. Conclusion: The top hat procedure did not alter the final diagnosis of LEEP. No impact on relapse was observed. The procedure should be avoided in women of reproductive age.

Asunto(s)

Humanos , Femenino , Procedimientos Quirúrgicos Ginecológicos , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Cuello del Útero , Colposcopía , Conización , Electrocirugia

RESUMEN

Objetivo: La biopsia guiada por colposcopia (BGC) marca el manejo de la neoplasia intraepitelial cervical. El objetivo de este estudio fue evaluar la concordancia de los resultados entre la BGC y la escisión amplia de la zona de transformación (LLETZ, large loop excision of the transformation zone), y la utilidad del genotipado del virus del papiloma humano (VPH) para seleccionar a las pacientes con riesgo de lesión intraepitelial escamosa de alto grado/neoplasia intraepitelial cervical 3 (HSIL/CIN3). Método: Se compararon los resultados de la BGC y de la LLETZ, siendo esta última el método de referencia. Se evaluó la relación del genotipo del VPH con el diagnóstico final de HSIL/CIN3. Resultados: La precisión de la biopsia comparada con LLETZ fue del 61,4%. La tasa de concordancia fue del 64,4% para CIN1, del 31,4% para CIN2 y del 77,4% para CIN3. La tasa global de sobrediagnóstico fue del 18,68% y la de subdiagnóstico del 19,89%. En mujeres menores de 30 años, la concordancia fue del 62,79% (CIN1 65%, CIN2 39,58% y CIN3 73,08%), la tasa de sobrediagnóstico del 22,67% y la tasa de subdiagnóstico del 15,11%. La infección por VPH16 tuvo una odds ratio de 3,86 para el diagnóstico final de HSIL/CIN3+. Conclusiones: El diagnóstico de CIN2 por BGC parece insuficiente para seleccionar a las pacientes para tratamiento escisional, principalmente en mujeres jóvenes. El hallazgo de VPH16 es un factor de riesgo de HSIL/CIN3+ independientemente del resultado de la biopsia.

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Objective: Colposcopy-guided biopsy (CGB) is a basic tool for the management of cervical intraepithelial neoplasia. The aim of this study is to evaluate the concordance of results between CGB and large loop excision of the transformation zone (LLETZ), and the usefulness of human papillomavirus (HPV) genotyping to select patients at risk of H-SIL/CIN3. Method: The results of colposcopy-guided biopsy and LLETZ were compared, with LLETZ being the gold standard. The relationship of HPV genotype to the final diagnosis of CIN3 was assessed. Results: The accuracy of CGB compared to LLETZ was 61.4%. The concordance rate was 64.4% for CIN1, 31.4% for CIN2 and 77.4% for CIN3. The overall overdiagnosis rate was 18.68% and underdiagnosis rate was 19.89%. In women under 30 years of age the concordance rate was 62.79% (CIN1 65%, CIN2 39.58% and CIN3 73.08%), and the rate of overdiagnosis and underdiagnosis was 22.67% and 15.11%, respectively. HPV16 infection had an odds ratio of 3.86 for the final diagnosis of CIN3+ and the result was significant regardless of the biopsy result. Conclusions: The CGB result as CIN2 is inaccurate and seems insufficient to select patients for excisional treatment, mainly in young women. HPV16 infection is a risk factor for CIN3+ regardless of the colposcopy-guided biopsy result.

Asunto(s)

Humanos , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Biopsia/métodos , Displasia del Cuello del Útero/genética , Displasia del Cuello del Útero/patología , Colposcopía/métodos , Lesiones Precancerosas , Estudios Retrospectivos , Técnicas de Genotipaje , Biopsia Guiada por Imagen , Genotipo , Papillomaviridae/genética

RESUMEN

The activin-follistatin system regulates several cellular processes, including differentiation and tumorigenesis. We hypothesized that the immunostaining of ßA-activin and follistatin varies in neoplastic cervical lesions. Cervical paraffin-embedded tissues from 162 patients sorted in control (n = 15), cervical intraepithelial neoplasia (CIN) grade 1 (n = 38), CIN2 (n = 37), CIN3 (n = 39), and squamous cell carcinoma (SCC; n = 33) groups were examined for ßA-activin and follistatin immunostaining. Human papillomavirus (HPV) detection and genotyping were performed by PCR and immunohistochemistry. Sixteen samples were inconclusive for HPV detection. In total, 93% of the specimens exhibited HPV positivity, which increased with patient age. The most detected high-risk (HR)-HPV type was HPV16 (41.2%) followed by HPV18 (16%). The immunostaining of cytoplasmatic ßA-activin and follistatin was higher than nuclear immunostaining in all cervical epithelium layers of the CIN1, CIN2, CIN3, and SCC groups. A significant decrease (p < 0.05) in the cytoplasmic and nuclear immunostaining of ßA-activin was detected in all cervical epithelial layers from the control to the CIN1, CIN2, CIN3, and SCC groups. Only nuclear follistatin immunostaining exhibited a significant reduction (p < 0.05) in specific epithelial layers of cervical tissues from CIN1, CIN2, CIN3, and SCC compared to the control. Decreased immunostaining of cervical ßA-activin and follistatin at specific stages of CIN progression suggests that the activin-follistatin system participates in the loss of the differentiation control of pre-neoplastic and neoplastic cervical specimens predominantly positive for HPV.

Asunto(s)

Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Virus del Papiloma Humano , Folistatina , Papillomaviridae/genética

RESUMEN

Background: Cervical cancer (CaCU) is the second cancer-related cause of death for women in Mexico. Early diagnosis and monitoring of patients by cervical cytology and colposcopy are currently the preferred screening methods for identification and prevention of this disease. Objective: To describe the epidemiological panorama of cervical dysplasia diagnosed in a first-level care hospital. Methods: The study was observational, retrospective, unicentric, homodemic, transversal. Records from 6,207 women who attended the General Subzone Hospital with Familiar Medicine #8 (HGSZ/UMF 8), in Tlaxcala, Mexico were analyzed. First-time cervical cytologies were analyzed from 2019 to 2021. Results: Cervical dysplasia was found in 2.6% of the patients being the most frequent type of dysplasia NIC 1. Most of the clinical characteristics of patients with dysplasia were in agreement with those of the Mexican population. Important differences were found (comorbilities, mass index, number of sexual partners, births, positivity to changes related to HPV and vaccination) between two population sets defined by age (younger and older than 40 years). Conclusions: The only factor where a tendency to be associated to type 2 and 3 dysplasia in the population younger than 40 years was the sexually active onset of life younger than 18 years, so this possible association should be evaluated in a bigger population. Our data suggests that risks factors should be evaluated separately for these age groups due to important differences regarding their clinic and epidemiological characteristics as well as changes in risk factor exposure.

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Introducción: en México, el cáncer cervicouterino (CaCU) es la segunda causa de mortalidad por cáncer en mujeres. El diagnóstico temprano y monitoreo mediante la citología cervicovaginal y la colposcopía son actualmente los métodos de tamizaje de elección para identificar y prevenir esta enfermedad. Objetivo: describir el panorama epidemiológico de displasias cervicales en un hospital de primer nivel de atención. Métodos: estudio observacional, retrospectivo, unicéntrico, homodémico, transversal. Se analizaron los expedientes de 6207 mujeres atendidas en el HGSZ/UMF No. 8, en Tlaxcala, con citologías vaginales de primera vez, durante 2019-2021. Resultados: se encontró displasia en el 2.6% de las pacientes. El tipo de displasia más frecuente fue NIC 1. Las características clínicas de las pacientes con displasia corresponden a las reportadas en población mexicana, pero se encontraron diferencias importantes (comorbilidades, IMC, NPS, gestas, positividad para cambios asociados al VPH y vacunación) entre dos tipos de población etaria (menores y mayores de 40 años). Conclusiones: el único factor donde hubo una tendencia de asociación al desarrollo de displasia tipo 2 y 3 en la población de más de 40 años fue el inicio de la vida sexual activa antes de los 18 años, por lo que se recomienda buscar una asociación en una población de mayor tamaño y evaluar factores de riesgo en los grupos etarios de manera separada por sus diferencias clínicas, epidemiológicas y factores de riesgo a los que están expuestas.

Asunto(s)

Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Embarazo , Adulto , Estudios Retrospectivos , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Frotis Vaginal , Colposcopía/efectos adversos , Tamizaje Masivo/efectos adversos , Tamizaje Masivo/métodos , Detección Precoz del Cáncer/efectos adversos , Detección Precoz del Cáncer/métodos , Papillomaviridae

RESUMEN

BACKGROUND: Some studies reported that differential gene expression could be used as a biomarker for high-grade cervical lesion identification. The aim was to evaluate the gene expression profile of cervical intraepithelial neoplasia (CIN) to identify a gene expression signature of CIN2+ in liquid-based cytology (LBC) samples. METHODS: LBC samples (n = 85) obtained from women who underwent colposcopy were included with benign (n = 13), CIN1 (n = 26), CIN2 (n = 16), and CIN3 (n = 30) diagnoses. After RNA isolation, gene expression profiling was performed using the nCounter PanCancer Pathways, which consists of 730 cancer-related genes. The genes identified were in silico expression evaluated using the UALCAN database. An accurate prediction model to discriminate CIN2+ from

Asunto(s)

Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Embarazo , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Citología , Cuello del Útero/patología , Displasia del Cuello del Útero/diagnóstico , Citodiagnóstico , Colposcopía , Infecciones por Papillomavirus/diagnóstico , Papillomaviridae/genética , Proteína Morfogenética Ósea 7 , Proteínas de la Membrana , Proteínas Tirosina Quinasas , Proteínas Serina-Treonina Quinasas

RESUMEN

BACKGROUND: The prevalence of Human Papillomavirus (HPV) infection in the general population is widely known, however, there are still few studies related to this infection in minority groups, Thus, the objective is to analyze the frequency of human papillomavirus and associated factors in quilombola and gypsy women. METHODS: Cross-sectional research with 145 quilombola and gypsy women from Caxias, Maranhão. Two Pap smear collections were performed and a questionnaire with 46 questions was applied between January, 2020 and March, 2021. Descriptive analysis and Odds Ratio with 95% confidence interval were performed. The research was approved by the ethics committee. RESULTS: There were 09 cases of atypia. The frequency of human papillomavirus was 41.37%, with a higher risk in quilombolas 55 (91.70%). Multiple infections were prevalent (53%) with high-risk genotypes 21 (35%). Types 16 and 18 together accounted for 42.85% of cases. CONCLUSIONS: The frequency of human papillomavirus infection was higher than those recorded in the Northeast and Brazil, and therefore type 16 predominated. Due to limitations, the virus lineages and sublineages were not evaluated. Quilombola women had a higher rate of infection than gypsies.

Asunto(s)

Infecciones por Papillomavirus , Romaní , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Estudios Transversales , Virus del Papiloma Humano , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Displasia del Cuello del Útero/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Grupos Minoritarios , Adolescente , Adulto , Persona de Mediana Edad , Brasil

RESUMEN

Background and Objectives: REST (RE1-silencing transcription factor) diminution is associated with transcriptional relaxation, neuropeptide overexpression, and phenotype redefinition in neuroendocrine cancers, but this effect has barely been studied in cervical cancer (CC). We previously reported reduced expressions of REST in samples with premalignant lesions and CC; however, the transcriptional consequences for neural genes associated with reduced REST expression in CC are unknown. Therefore, the objective of this work was to evaluate the expression of neuronal genes in cancerous cells with reduced expression levels of REST. Materials and Methods: Here, we monitored levels of REST by immunostaining along the premalignant lesions and in invasive cervical squamous cell carcinoma (SCC) and endocervical adenocarcinoma (ADC) in tissue samples from female patients from southern Mexico and the derivative cell lines SiHa and HeLa, respectively. Next, we selected REST target genes in silico and explored the effect of REST silencing by RT-PCR in siRNA-treated HeLa cells. Results: The results show a REST diminution in premalignant lesions, SCC, ADC, and cancerous cell lines. Further REST silencing in HeLa cells altered the expression of genes containing the RE1 (Restrictive Element 1) sequence, including CgA (chromogranin A), CHRNß2 (cholinergic receptor nicotinic ß 2 subunit), BDNF (brain-derived neurotrophic factor), CRF (corticotropin-releasing factor), and RASSF1A (Ras association domain family 1). Conclusions: This work provides preliminary evidence of the role of REST loss in the transcriptional regulation of its target genes in HeLa cells, which could have positive implications for the search for new biomarkers of cervical cancer.

Asunto(s)

Proteínas Represoras , Factores de Transcripción , Neoplasias del Cuello Uterino , Femenino , Humanos , Biomarcadores , Expresión Génica , Células HeLa , ARN Interferente Pequeño , Factores de Transcripción/genética , Neoplasias del Cuello Uterino/genética , Proteínas Represoras/genética

RESUMEN

BACKGROUND: The objective was to determine the prevalence of abnormal cytologic smears in a large population of a Brazilian city. METHODS: Retrospective study of cervical cytology results performed at a private laboratory in São Paulo - Brazil. A total of 1,030,482 cytology tests were performed between January 2010 and December 2015. RESULTS: Among the satisfactory cytologies, we observed abnormal results in 8.9% (91,371). Analyzing the proportion of exams with altered results over the years, there was no change in these rates. We observed that the proportion of abnormal exams decreased with increasing age. Atypical squamous cells of undetermined significance, possibly non-neoplastic (ASC-US) cytology was the most common abnormality found in the general population with 73.19%, followed by low-grade intraepithelial lesion (LSIL) with 20.5%; these 2 cytological abnormalities add up to 93.69 % of all abnormal results. There was an increase in ASC-US with advancing age, a decrease in prevalence of LSIL, especially after the age of 30 and high-grade intraepithelial lesion (HSIL) shows two peaks of elevation, respectively in the age groups of 30-39 years and over 70 years. CONCLUSION: Women under the age of 30 showed a higher prevalence of cytological abnormalities, however most of these changes are low-grade lesions. In older women, cytological abnormalities are largely high-grade lesions, requiring greater care to prevent progression to cancer.

Asunto(s)

Células Escamosas Atípicas del Cuello del Útero , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Anciano , Adulto , Frotis Vaginal , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Prueba de Papanicolaou , Brasil/epidemiología , Estudios Retrospectivos , Células Escamosas Atípicas del Cuello del Útero/patología

RESUMEN

Cervical cancer is still one of the leading causes of cancer and mortality in women, especially in low- and middle-income countries. Normally, the prevention of its occurrence is done through efficient screening and treatment programs for high-grade epithelial lesions, which are pre-malignant lesions. Cheaper diagnostic techniques ensure greater access to women, which can prevent a large number of cancer cases worldwide. Objective: The aim of the study was to evaluate the accuracy of visual inspection either with acetic acid or with Lugol's iodine, cervical cytology and colposcopy in the diagnosis of cervical intraepithelial neoplasia 2 and 3. Methods: This is a study of diagnostic accuracy. We evaluated 115 women with high-grade squamous intraepithelial lesion confirmed by biopsy, 54 with cervical intraepithelial neoplasia 2 and 61 with cervical intraepithelial neoplasia 3, from January 2016 to December 2018 at the Lower Genital Tract Pathology and Colposcopy Service of the Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. A comparative analysis of the visual inspection, Pap smear and colposcopy diagnostic methods was performed. Results: The average age was 33.1 years (standard deviation=9.83) for cervical intraepithelial neoplasia 2 cases and 35.2 years (standard deviation=7.97) for cervical intraepithelial neoplasia 3. In the cervical intraepithelial neoplasia 2 group, visual inspection tests were positive for high-grade squamous intraepithelial lesion in 98.1% of the cases with acetic acid and 94.4% with Lugol's iodine. Colposcopy identified a probable high-grade squamous intraepithelial lesion in 94.4% of the cases, while cytology only in 42.6%. In the cervical intraepithelial neoplasia 3 group, the visual inspection tests were positive for high-grade squamous intraepithelial lesion in 91.8% of the cases with acetic acid and 95.1% with Lugol's iodine. Colposcopy identified a probable high-grade squamous intraepithelial lesion in 93.5% of the cases, while cytology in 65.6%. Conclusion: Visual inspection with acetic acid and Lugol's iodine, and colposcopy test were more accurate for the diagnosis of cervical intraepithelial neoplasia 2 and 3 than through cytopathology. (AU)

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Introdução: O câncer do colo de útero ainda é uma das principais causas de câncer e mortalidade em mulheres, especialmente em países de baixa e média renda. Normalmente, a prevenção de sua ocorrência é feita por meio de programas eficientes de triagem e tratamento de lesões epiteliais de alto grau, que são as lesões pré-malignas. Técnicas diagnósticas mais baratas garantem maior acesso às mulheres, podendo evitar um grande número de casos de câncer no mundo inteiro. Objetivo: O objetivo deste estudo foi avaliar a acurácia da inspeção visual (com ácido acético e com solução de lugol), da citologia cervical e da colposcopia no diagnóstico de neoplasias intraepiteliais cervicais 2/3. Métodos: Trata-se de um estudo de acurácia diagnóstica. Foram avaliadas 115 mulheres com lesão intraepitelial escamosa de alto grau confirmada por biópsia, 54 com neoplasias intraepiteliais cervicais 2 e 61 com neoplasias intraepiteliais cervicais 3, no período de janeiro de 2016 a dezembro de 2018 no Serviço de Patologia e Colposcopia do Trato Genital Inferior do Hospital de Clínicas de Porto Alegre, em Porto Alegre, Brasil. Foi realizada análise comparativa dos métodos de diagnóstico Inspeção visual com ácido acético, Inspeção visual com Solução de Lugol, colpocitologia oncótica e colposcopia. Resultados: A média de idade foi de 33,11 anos (DP 9,83) para os casos de neoplasias intraepiteliais cervicais 2 e de 35,28 anos (DP 7,97) para neoplasias intraepiteliais cervicais 3. No grupo de neoplasias intraepiteliais cervicais 2, os testes de inspeção visual foram positivos para tratamento de lesões epiteliais de alto grau em 98,1% dos casos com Inspeção visual com ácido acético e em 94,4% daqueles com Inspeção visual com Solução de Lugol. A colposcopia identificou provável tratamento de lesões epiteliais de alto grau em 94,4% dos casos, enquanto a citologia apenas 42,6%. No grupo neoplasias intraepiteliais cervicais 3, os testes de inspeção visual foram positivos para tratamento de lesões epiteliais de alto grau em 91,8% dos casos com Inspeção visual com ácido acético e em 95,1% daqueles com Inspeção visual com Solução de Lugol. A colposcopia identificou provável tratamento de lesões epiteliais de alto grau em 93,5% dos casos, enquanto a citologia em 65,6%. Conclusão: A inspeção visual (com ácido acético e com Solução de Lugol) e a colposcopia foram mais precisas para o diagnóstico de neoplasias intraepiteliais cervicais 2/3 do que a citopatologia. (AU)

Asunto(s)

Humanos , Femenino , Adulto , Adulto Joven , Displasia del Cuello del Útero/diagnóstico , Colposcopía , Prueba de Papanicolaou , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Detección Precoz del Cáncer

RESUMEN

OBJECTIVE: To detect factors related to overtreatment with the "Screen-and-treat" approach (S&T) in women with suspicious cervical precancerous lesions. STUDY DESIGN: A retrospective observational study of 524 women with high-grade squamous intraepithelial lesions (HSIL) or more severe (HSIL+) in cytology, treated by the Large Loop Excision of the Transformation Zone (LLETZ): 161 without a previous biopsy (S&T group) and 363 with a previous biopsy (biopsy group) from January 2017 to July 2020. The main outcome was a diagnosis of LLETZ: negative (negative or low-grade squamous intraepithlelial lesion LSIL) or HSIL+. A negative diagnosis was interpreted as "overtreatment." Results were analyzed as a function of the S&T approach (whether previous biopsy or not). Variables were obtained from medical records, and were compared with Chi-square or Fisher's exact test (p, p-value), to estimate the chances of a logistic regression analysis (Odds Ratio, OR, or admitting a Confidence Interval (CI) of 95 %). RESULTS: No differences were observed in groups regarding menopausal status, smoking, hormonal contraceptive use, colposcopy findings, LLETZ diagnosis, and recurrence. Comparing biopsy vs S&T groups, the frequency of women over 40 years was 28.4 % vs 39.7 % (p = 0.011), and transformation zone type 3 was 12.2 vs 26.8 % (p < 0.001), respectively. In women managed by S&T, when compared to a LLETZ diagnosis, an HSIL+ result was more frequent in women presenting with TZ 1 (93.1 % TZ1 vs 78.5 % TZ2 vs 73.8 % TZ3, p = 0.008) and in women with abnormal colposcopy (92.9 % abnormal vs 38.1 % negative, p < 0.001). Multiple regression analysis found that women with negative colposcopic findings presented a higher risk for negative LLETZ diagnosis (LSIL/Negative final histology) (18.6; 6.18-56.02). CONCLUSIONS: No difference was observed in the LLETZ diagnosis in women who did or did not use the S&T approach: it was adequate for women referred by cytological HSIL along with high-grade colposcopic findings.

Asunto(s)

Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Embarazo , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/diagnóstico , Cuello del Útero/patología , Colposcopía/métodos , Biopsia

RESUMEN

ABSTRACT Background: Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors. Methods: This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH. Results: From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037). Conclusions: The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access.

RESUMEN

Objetivo: nuestro objetivo principal fue evaluar la prevalencia de citología anal patológica en mujeres con antecedentes de neoplasia intraepitelial cervical. Métodos: se trata de un estudio de cohorte transversal desde mayo de 2018 a agosto de 2020 en el Centro Hospitalario Pereira Rossell. Se estudiaron dos cohortes: una de mujeres que tenían diagnóstico de neoplasia intraepitelial cervical y otra de control de mujeres sanas que asistieron al control, con una proporción de 2:1. Se calculó un tamaño muestral total de 205 pacientes, siendo 135 pacientes con NIC con un IC del 95%, suponiendo una prevalencia del 10% de lesiones preneoplásicas anales. El tamaño muestral de la cohorte control fue de 70 pacientes según la relación preestablecida. Resultados: se encontró asociación entre la presencia de lesiones premalignas cervicales y anomalías epiteliales detectadas en la citología anal, con un cociente de prevalencia de 1,77 (IC del 95%: 1,19-2,62) y un odds ratio de 2,69 (1,36-5,30). No se encontraron diferencias significativas en las variables de raza, tipo de relación sexual o tabaquismo. Conclusiones: nuestro estudio concluye que existe una asociación entre la neoplasia intraepitelial cervical relacionada con el VPH y la citología anal patológica.

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Objective: the main objective of the study was to assess the prevalence of anal cytology in women with a history of cervical intraepithelial neoplasia. Method: cohort transversal study conducted from May, 2018 until August, 2020 at Pereira Rossell Hospital. Two cohorts were studied, one of which included women with a diagnosis of cervical intraepithelial neoplasia and the other one included healthy women who attended their routine follow up, in a 2:1 ratio. The total size of the sample was 205 patients, 135 of which were patients with cervical intraepithelial neoplasia (confidence interval being 95%), presuming a 10% prevalence of anal pre-neoplasic lesions. The sample size of the control cohort was 70 patients as per the pre-defined ratio. Results: a association was found between the presence of malignant lesions of the cervix and epithelial anomalies detected in the anal cytology, with a prevalence coefficient of 1.77 (CI: 95%: 1,19 - 2,62) and odds ratio of 2,69 (1,36 - 5,30). No significant differences were found between race, type of sexual relationships or smoking variables. Conclusions: our study concludes there is an association between cervical intraepithelial neoplasia related to HPV and pathological anal screening.

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Objetivo: Avaliar a prevalência de citologia anal patológica em mulheres com história de neoplasia intraepitelial cervical. Métodos: Trata-se de um estudo de coorte transversal de maio de 2018 a agosto de 2020, no Hospital Pereira Rossell. Foram estudadas duas coortes, uma de mulheres com diagnóstico de neoplasia intraepitelial cervical e outra de controle de mulheres saudáveis que compareceram ao controle na proporção de 2:1. Foi calculada uma amostra total de 205 pacientes, 135 pacientes com NIC com um IC de 95%, assumindo uma prevalência de 10% de lesões pré-neoplásicas anais. O tamanho da amostra da coorte controle foi de 70 pacientes de acordo com a relação pré-estabelecida. Resultados: Foi encontrada associação entre a presença de lesões pré-malignas cervicais e anormalidades epiteliais detectadas na citologia anal, com razão de prevalência de 1,77 (IC 95%: 1,19 - 2,62) e odds ratio 2,69 (1,36-5,30). Não foram encontradas diferenças significativas nas variáveis raça, tipo de relação sexual ou tabagismo. Conclusões: Nossos resultados mostram uma associação entre neoplasia intraepitelial cervical relacionada ao HPV e citologia anal patológica.

Asunto(s)

Humanos , Femenino , Displasia del Cuello del Útero , Tamizaje Masivo , Papillomaviridae

RESUMEN

Introducción: la pandemia por COVID-19 ha afectado la salud de la mujer y en particular a los derechos sexuales y reproductivos. En el contexto de cambios asistenciales por la pandemia COVID 19, podría verse afectado el tamizaje y seguimiento de las lesiones premalignas de los cánceres de cuello de útero (CCU), poniendo en riesgo su diagnóstico oportuno y tratamiento precoz. El objetivo de este estudio es reportar los tiempos transcurridos entre el resultado de screening patológico y el tratamiento de lesiones premalignas de CCU, cotejando con los plazos establecidos por la ordenanza ministerial vigente y comparando los tiempos observados antes y durante la pandemia. Métodos: se realizó un estudio observacional, analítico, de corte transversal, mediante un análisis comparativo antes y después de la pandemia por COVID-19. Se incluyeron usuarias a quienes se les realizó conización quirúrgica en el Centro Hospitalario Pereira Rossell en dos períodos de tiempo: 1 de marzo de 2019 a 29 de febrero de 2020, y 1 de marzo de 2020 a 28 de febrero de 2021. Resultados: la media en días observada desde el PAP hasta la conización fue de 245 para el primer periodo y de 242 para el segundo. El porcentaje de pacientes que cumplen con la ordenanza ministerial en ambos períodos no supera el 5%. Conclusiones: no se evidenció una mayor demora en el seguimiento y tratamiento de estas usuarias durante la pandemia por COVID-19, sin embargo los tiempos observados superan ampliamente los establecidos por Ordenanza Ministerial en los periodos pre pandemia y durante la misma.

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Introduction: the COVID-19 pandemic has affected women's health in general, and in particular their sexual and reproductive rights. Within the context of changes in health care services due to the COVID-19 pandemic, the screening and follow up of cervical precancerous lesions could be affected, and in turn, this could prevent timely diagnosis and early treatment. This study aims to report the period of time be-tween pathological findings in screening tests and the treatment of precancerous lesions of cervical cancer, analyze it within the context of deadlines set in the Ministry of Health regulations in force, and compare it to pre-pandemic deadlines and time frames during the COVID-19 pandemic. Method: observational, analytical and transversal study conducted by means of analyzing the situation before and after the COVID-19 pandemic. The study included users who underwent surgical conization at the Pereira Rossell Hospital during two periods of time: Between March 1, 2019 and February 29, 2020 and between March 1, 2020 and February 28, 2021. Results: average number of days from the PAP test until conization was 245 days for the first period and 242 for the second one. The percentage of patients that comply with the Ministerial decree in both periods is lower than 5%. Conclusions: the study found time to treatment in the follow up and management of users did not increase during the COVID-19 pandemic. However, the times ob-served widely exceed the deadlines set in the ministerial decree in both periods, that is before and during the pandemic.

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Introdução: a pandemia de COVID-19 afetou a saúde das mulheres e em particular os direitos sexuais e reprodutivos. No contexto das mudanças na saúde devido à pandemia de COVID 19, o rastreamento e o acompanhamento das lesões pré-malignas do câncer de colo de útero (CCU) podem ser afetados, colocando em risco o diagnóstico oportuno e o tratamento precoce. Objetivo: descrever os tempos decorridos entre o resultado do rastreamento patológico e o tratamento das lesões pré-malignas do CCU, comparando-os com os períodos estabelecidos pela atual Portaria Ministerial, e comparar os tempos observados antes e durante a pandemia. Métodos: foi realizado um estudo observacional, analítico e transversal por meio de uma análise comparativa antes e após a pandemia de COVID19. Foram incluídos as usuárias que realizaram a conização cirúrgica no Hospital Pereira Rossell em dois períodos de tempo: 1º de março de 2019 a 29 de fevereiro de 2020 e 1º de março de 2020 a 28 de fevereiro de 2021. Resultados: a média de dias observados do PAP à conização foi de 245 para o primeiro período e 242 para o segundo. O percentual de pacientes que cumprem a Portaria Ministerial em ambos os períodos não ultrapassa 5%. Conclusões: não houve evidência de maior demora no acompanhamento e tratamento desses usuários durante a pandemia por COVID-19, porém os tempos observados superam em muito os estabelecidos por Portaria Ministerial nos períodos pré-pandemia e durante a mesma.

Asunto(s)

Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/terapia , Detección Precoz del Cáncer , Tiempo de Tratamiento , COVID-19 , Displasia del Cuello del Útero , Tamizaje Masivo

RESUMEN

BACKGROUND: Cervical cancer is a preventable disease, but it is a major public health problem despite having a good prognosis when diagnosed early. Although the Pap smear has led to huge drops in rates of cervical cancer and death from the disease, it has some limitations, making new approaches necessary for early diagnosis and biomarkers discovery. MiRNAs have been considered a new class of non-invasive biomarkers and may have great clinical value for screening early-stage cervical intraepithelial neoplasia. Well-designed studies have emerged as a necessary strategy for the identification of miRNAs that could be used safely and reliably for a differential diagnosis. This review aims to provide an up-to-date perspective on the assessment of circulating miRNA expression from precursor lesions to cervical cancer, identifying circulating miRNAs or specific miRNA signatures that can be used as potential biomarkers of different stages of cervical carcinogenesis. METHODS: A systematic review was performed and searches were conducted in the PubMed, LILACS, and Scopus electronic databases. RESULTS: Most studies involved Chinese ethnic women and searched for circulating miRNAs in serum samples. Thirty three microRNAs were evaluated in the eligible studies and 17 (miR-196a, miR-16-2, miR-497, miR-1290, miR-425-5p, hsa-miR- 92a, miR-1266, miR-9, miR-192, miR-205, miR-21, miR-152, miR-15b, miR-34a, miR-218, miR-199a-5p and miR-155-5p) showed up-regulation in women with precursor lesion and cervical cancer and 16 microRNAs showed decreased expression in these same groups of women compared to healthy controls (miR-195, miR-2861, miR-145, miR-214, miR-34a, miR-200a, let-7d-3p, miR-30d-5p, miR-638, miR-203a-3p, miR-1914-5p, miR-521, miR-125b, miR-370, miR-218 and miR-100). CONCLUSION: Therefore, defining promising circulating miRNAs or specific miRNA signatures of biological fluid samples can be useful for the screening, diagnosis, prognosis and clinical monitoring of women undergoing cervical carcinogenesis, but greater standardization of studies seems to be necessary for greater consolidation of information.

Asunto(s)

MicroARN Circulante , MicroARNs , Neoplasias del Cuello Uterino , Biomarcadores , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Detección Precoz del Cáncer , Femenino , Humanos , MicroARNs/genética , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética

RESUMEN

Objectives: To evaluate the outcomes of conservative management in young women with high-grade squamous intraepithelial lesion (HSIL). Methods: A retrospective cohort study included women younger than 30 years referred with HSIL (cytology or biopsy) managed conservatively from 2012 to 2019, in Campinas/Brazil. Regression was the outcome when no evidence of HSIL was observed in at least two consecutive follow-ups. Kaplan-Meyer method was used to determine regression probabilities. Other tests were chi-square or Fisher, Mann-Whitney and COX regression. Results: During the study period, 89 patients were included. No progression to microinvasive or invasive cancer was observed. Sixty-one (69%) patients were younger than 25 years, and 28 (31%) were aged 25-30 years. Spontaneous regression was seen in 64 (72%) and persistence in 25 (28%) of the overall sample. The average time to regression was 15.4 months (standard deviation [SD] = 7.7), and the follow-up time was 31.6 months (SD 19.0). Age, parity, first sexual intercourse, smoking, hormonal contraception, and colposcopy impression were not different among women with regression or persistence. Regression probabilities were, respectively, 28.9%, 60.2%, and 78.1% after 12, 18, and 24 months. Most of the events happened between 12 and 18 months of follow-up. Conclusions: Conservative management in women younger than 30 years was safe: spontaneous regression was observed in 72% of all women younger than 30 with HSIL managed conservatively. No clinical variable was relevant, influencing regression. In 2 years the regression probability was 78%.