International algorithms for the management of patients with uterine cervical dysplasia

Dobrokhotova, Yu.E.; Эдуардовна, Доброхотова Юлия; Боровкова, Е И; Игоревна, Боровкова Екатерина

doi:10.26442/2079-5696_2018.5.27-32

Cited by 4 publications

(1 citation statement)

References 3 publications

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“…CIN2 (умеренная дисплазия) имеет более выраженные изменения, затрагивающие 1 / 2 эпителиального слоя. CIN3 (тяжелая дисплазия) характеризуется поражением более 2 / 3 эпителиального слоя и появлением патологических митозов, а также наличием огромных гиперхромных ядер клеток [4]. Прогрессирование до интраэпителиальных предраковых заболеваний происходит из-за множественных нарушений в сигнальных путях, регулирующих клеточный цикл, вызванных избыточной экспрессией вирусных белков E6 и E7, которые функционально инактивируют продукты генов RB и TP53.…”

Section: Introductionunclassified

Differential expression of microRNAs and their target genes in cervical intraepithelial neoplasias of varying severity

Димитриади

Бурцев

Dzhenkova³

et al. 2020

Usp. mol. onkol

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Background. Currently, little is known about the specific microRNAs involved in the development of cervical intraepithelial neoplasia (CIN1, 2, 3) and the transition to cancer in situ (CIS). Our meta-analysis allowed us to isolate 8 microRNAs (hsa-miR-1246, hsa-miR- 145-5p, hsa-miR-196b-5p, hsa-miR-34a-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-375-5p, hsa-miR-96-5p) with potential significance in the progression of precancerous diseases to cervical cancer. Objective: to analyze the expression features of hsa-miR-1246, hsa-miR-145-5p, hsa-miR-196b-5p, hsa-miR-34a-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-375-5p, hsa-miR-96-5p and their target genes, as well as genes associated with them in common signaling pathways in the tissues of the cervix in patients with CIN1–3 and CIS. Materials and methods. To assess the expression level of microRNA and matrixRNA, the quantitative polymerase chain reaction in real time method was used. Data analysis was carried out in the Python programming language using the SciPy library. Search for target genes was performed using the TarPmiR algorithm and the overrepresentation of microRNAs in signaling pathways (Over-Representation Analysis) was analyzed. To identify genes associated with target genes in common signaling pathways, GIANT (Genome-scale Integrated Analysis of gene Networks in Tissues) and network integration with several associations algorithms were used. Results. For microRNAs miR-145, miR-196b, miR-34a, miR-20a, miR-21, miR-375 and miR-96 a decrease in expression was found in the subgroup of patients with CIS, while for 4 microRNAs (miR-145, miR-34a, miR-20a and miR-375), an increase in the expression level was found for CIN1, 2. The detected features of microRNA expression in subgroups of patients with CIN1–3 and CIS also affected the expression of their target genes (CDKN2A, MKI67, TOP2A and CD82), as well as the genes associated with them in common signaling pathways (PGK1, THBS4 (TSP4) and ECM1). Conclusion. Thus, the study revealed that each degree of CIN is characterized by its own specific molecular profile – the differential expression of microRNAs, their target genes and the genes associated with them in the general signaling pathways.

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Section: Introductionunclassified

Differential expression of microRNAs and their target genes in cervical intraepithelial neoplasias of varying severity

Димитриади

Бурцев

Dzhenkova³

et al. 2020

Usp. mol. onkol

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Prognostic value of microRNA assessment in cervical epithelial cells of patients with mild dysplasia

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Присяжная

Zabegina

et al. 2021

Opuholi ženskoj reproduktivnoj sistemy

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Background. Currently, there are no reliable markers for the prognosis of the low-grade squamous intraepithelial lesion (LSIL) of the cervical epithelium. Scientific literature provides with inconsistent recommendations regarding the management of the young patients with a cytological diagnosis of LSIL. The progression of cervical dysplasia and the development of cervical cancer are associated with characteristic alterations of the microRNA expression profile.Objective: to assess the prognostic value of microRNA in LSIL. Materials and methods. Samples (cytological smears) obtained from patients diagnosed with LSIL (n = 36), but with a different course of the disease over the next 6–12 months. Analysis of miRNA expression was carried out by the method of “two-tailed” reverse transcription and subsequent PCR.Results. The expression level of miR-126, miR-21, miR-1246, miR-182 was statistically significantly different in the compared groups, but the predictive value of the analysis of individual molecules was low (AUC <0.65). Calculation of the concentration ratios of the “reciprocal” pairs of microRNAs made it possible to obtain a more effective prognostic marker. ROC analysis of such ratios (miR-126/miR-182, miR-21/miR-182, miR-1246/miR-182) yielded AUC values: 0.82–0.89, sensitivity: 0.71–0.92; specificity: 0.86.Conclusions. Analysis of a panel of microRNA marker molecules in the material of the cervical epithelium and calculation of the concentration ratios of “reciprocal” pairs is a promising method for prognosis of LSIL course.

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Vulvovaginitis and their correction in patients with cervical HPV-associated diseases in the light of the doctrine of pathomorphosis

et al. 2021

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Background. Biological pathomorphosis of the leading pathogens of the vaginal microecological system with the occurrence of vulvovaginitis in human papillomavirus (HPV)-associated cervical intraepithelial neoplasia (CIN) is a fundamental prerequisite for optimizing the complex treatment of this disease. Aim. Optimization of treatment of vulvovaginitis based on the study of the pathomorphism of their pathogens in patients with HPV-associated CIN. Materials and methods. A two-stage examination of 211 patients with HPV-associated CIN I was carried out from 2013 to 2020. To study the pathomorphosis of the disease, the patients were divided into 2 groups, the 1st group was examined in 20132016, the 2nd in 20172020. The study of microbiocenosis was carried out by RT-PCR using Femoflor-16 reagents. At the second stage, a study of the clinical efficacy of treatment of vulvovaginitis with the complex drug nifuratel 500 mg + nystatin 200 thousand IU (Macmiror Complex) in comparison with metronidazole 500 mg. Results and discussion. It was revealed that patients with HPV-associated CIN I over the last 8 years have a pathomorphosis of pathogens. In particular, the change in the dominance of anaerobic dysbiosis with the highest bacterial replication of Gardnerella vaginalis in association with Clostridium, Megasphaera spp. and Fusobacterium on the mixed nature of microflora, manifested in the form of vulvaginitis with the dominance of Atopobium vaginae in association with G. vaginalis, Ureaplasma (urealyticum + parvum) and the addition of the intestinal group Enterobacteriaceae spp. and Escherichia coli. The use of the complex drug nifuratel 500 mg + nystatin 200 thousand IU (Macmiror Complex) demonstrated a higher (4 times) clinical efficacy, a 12-fold decrease in the recurrence of the inflammatory process compared with metronidazole in the treatment of vulvovaginitis in patients with CIN I. Conclusions. 1. The structure of the cervico-vaginal microbiota in HPV-associated CIN I degree is characterized by dysbiotic disorders in 68.3% of cases. During the last 8 years, there was a pathomorphosis of the microecological status from the dominant anaerobic (in 74.2% of cases, =9.39 at p=0.001) to the dominant mixed (in 60.8% of cases, =8.54 at p=0.001 ) with the addition of the intestinal group Enterobacteriaceae spp. and E. coli in 60.8% of patients (=9.59 at p=0.001), which indicated a change in the dominant causative agents of vulvovaginitis in CIN I. 2. Comparative analysis of the clinical efficacy of complex drugs has demonstrated an increase in clinical efficacy when using the drug nifuratel 500 mg + nystatin 200 thousand IU by 4 times, a decrease in the recurrence of the inflammatory process by 12 times, compared with standard therapy with metronidazole, which allows us to recommend inclusion of the drug nifuratel 500 mg + nystatin 200 thousand IU in the therapy of vulvovaginitis in patients with CIN I.

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International algorithms for the management of patients with uterine cervical dysplasia

Abstract: The article presents the algorithms of patient management, depending on the results of smear on oncology and in accordance with the age of the patient.

Cited by 4 publications

References 3 publications

Differential expression of microRNAs and their target genes in cervical intraepithelial neoplasias of varying severity

Differential expression of microRNAs and their target genes in cervical intraepithelial neoplasias of varying severity

Prognostic value of microRNA assessment in cervical epithelial cells of patients with mild dysplasia

Vulvovaginitis and their correction in patients with cervical HPV-associated diseases in the light of the doctrine of pathomorphosis

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