scholarly journals MicroRNA Biomarkers of High-Grade Cervical Intraepithelial Neoplasia in Liquid Biopsy

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Rhafaela L. Causin ◽  
Luciane S. da Silva ◽  
Adriane F. Evangelista ◽  
Letícia F. Leal ◽  
Karen C. B. Souza ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Progression ◽  
Mirna Expression ◽  
Liquid Biopsy ◽  
Intraepithelial Neoplasia ◽  
Differentially Expressed ◽  
Molecular Pathways ◽  
Precursor Lesions ◽  
Nanostring Technology

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

scholarly journals Upregulation of Translationally Controlled Tumor Protein Is Associated With Cervical Cancer Progression

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoyu Zhu ◽  
Ji Ren ◽  
Dianqin Xu ◽  
Di Cheng ◽  
Wei Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Cell Lines ◽  
Cancer Progression ◽  
Protein Interactions ◽  
Intraepithelial Neoplasia ◽  
Cancer Tissue ◽  
Functional Protein ◽  
Translationally Controlled Tumor Protein ◽  
Potential Biomarker

Outside a few affluent countries with adequate vaccination and screening coverage, cervical cancer remains the leading cause of cancer-related deaths in women in many countries. Currently, a major problem is that a substantial proportion of patients are already at an advanced cancer stage when diagnosed. There is increasing evidence that indicates the involvement of translationally controlled tumor protein 1 (TPT1) overexpression in cancer development, but little is known about its implication in cervical cancer. We assessed the levels of TPT1 in surgical tissue and sera of patients with cervicitis, cervical intraepithelial neoplasia III, and cervical cancer, as well as in normal and cancerous cervical cell lines. Gene sets, pathways, and functional protein interactions associated with TPT1 were identified using the TCGA data cohort of cervical cancer. We found that the TPT1 expression was significantly increased in cervical cancer tissue compared to all nonmalignant cervical tissues, including samples of cervicitis, cervical intraepithelial neoplasia III, and normal controls. Serum level of TPT1 was also increased in cervical cancer patients compared to healthy subjects. Furthermore, elevated TPT1 expression was significantly correlated with lymph node metastasis and a low differentiation degree of the cancer. In the cancerous tissues and cell lines, selective markers of PI3K/AKT/mTOR pathway over-activation, apoptosis repression, and EMT were detected, and their interaction with TPT1 was supported by biometrics analyses. Our results, for the first time, demonstrate a strong correlation of upregulated TPT1 expression with cervical cancer progression, suggesting that TPT1 might provide a potential biomarker for cervical cancer progression.

scholarly journals The Role of the Cervicovaginal and Gut Microbiome in Cervical Intraepithelial Neoplasia and Cervical Cancer

2020 ◽  
Author(s):  
Travis T. Sims ◽  
Lauren E. Colbert ◽  
Ann H. Klopp
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Progression ◽  
Gut Microbiome ◽  
Therapeutic Response ◽  
Critical Role ◽  
Intraepithelial Neoplasia ◽  
Ongoing Research ◽  
Papilloma Virus

ABSTRACT The microbiome, which refers to the microbiota within a host and their collective genomes, has recently been demonstrated to play a critical role in cancer progression, metastasis, and therapeutic response. The microbiome is known to affect host immunity, but its influence on human papilloma virus (HPV) gynecologic malignancies remains limited and poorly understood. To date, studies have largely focused on the cervicovaginal microbiome; however, there is growing evidence that the gut microbiome may interact and substantially affect therapeutic response in gynecologic cancers. Importantly, new developments in microbiome sequencing and advanced bioinformatics technologies have enabled rapid advances in our understanding of the gut and local tumor microbiota. In this review, we examine the evidence supporting the role of the microbiome in HPV-associated cervical intraepithelial neoplasia (CIN) and cervical cancer, explore characteristics that influence and shape the host microbiota that impact HPV-driven carcinogenesis, and highlight potential approaches and considerations for future and ongoing research of the microbiome's effect on HPV-associated cancer.

scholarly journals The Trained Sniffer Dog Could Accurately Detect the Urine Samples from the Patients with Cervical Cancer, and Even Cervical Intraepithelial Neoplasia Grade 3: A Pilot Study

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3291
Author(s):  
Akihito Yamamoto ◽  
Seiryu Kamoi ◽  
Keisuke Kurose ◽  
Marie Ito ◽  
Toshiyuki Takeshita ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patient ◽  
Healthy Volunteers ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Progression ◽  
Intraepithelial Neoplasia ◽  
Urine Samples ◽  
Premalignant Lesions ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Grade 3

(1) Background: Previous reports have indicated that cancers of the stomach, lung, and pancreas can be detected by dog sniffing, but results have been varied. Here, a highly trained dog was used to determine whether urine from patients with cervical premalignant lesions and malignant tumors have a cancer-specific scent. (2) Methods: A total of 195 urine samples were collected from patients with cervical cancer, cervical intraepithelial neoplasia grade 3 (CIN3), benign uterine diseases, and healthy volunteers. Each test was performed using one urine sample from a cancer patient and four samples from different controls. Each of the five urine samples was placed in a separate box. When the cancer sniffing dog stopped and sat in front of the box with a sample from a cancer patient, the test was considered as positive. (3) Results: 83 patients with cervical cancer (34 cases of cervical cancer and 49 cases of cervical intraepithelial neoplasia grade 3), 49 patients with uterine benign diseases, and 63 healthy volunteers were enrolled, and their urine samples were collected. In 83 times out of 83 runs in a double-blind test, the trained dog could correctly identify urine samples of cervical cancer patients. (4) Conclusion: A trained dog could accurately distinguish the urine of all patients with cervical cancer or CIN3, regardless of the degree of cancer progression.

scholarly journals Successfully Pregnancy Outcome After LLETZ in Women with Cervical Intraepithelial Neoplasia: A Case Series

2021 ◽  
Vol 9 (C) ◽  
pp. 308-312
Author(s):  
Junita Indarti ◽  
Raymond Surya ◽  
Reyhan Aditya ◽  
Muhammad Ikhsan ◽  
Kristian Alda ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Progression ◽  
Precancerous Lesions ◽  
Case Series ◽  
Intraepithelial Neoplasia ◽  
Obstetric Outcomes ◽  
Hpv Testing ◽  
Large Loop ◽  
Cervical Cancer Development

BACKGROUND: Human papillomavirus (HPV) has an important role in cervical cancer development and the incidence of cervical intraepithelial neoplasia (CIN) was 1.3–2.7/1000 pregnancies. The HPV and its treatments such as loop electrosurgical excisional procedure (LEEP) or large loop electrosurgical excisional procedure (LLETZ) have an association with poor obstetric outcomes. CASE REPORT: Here, we present four case studies of successful live birth after treatment of CIN. We reported that four patients had been performed LLETZ, with abnormal colposcopy results and liquidbased cytology results were one ASCUS, one ASCH, and two HSIL. The histopathology results were one CIN 1, one CIN 2, and two CIN 3. There was a higher rate of pregnancy for treated women than untreated women. The higher the CIN grades, the more prevalence of cesarean section rate. CONCLUSION: The HPV testing or cotesting at 3-year intervals is recommended after treatment due to the sensitivity of HPV testing. Although pregnancy could delay the progression of precancerous lesions, it is recommended to follow the individualized algorithm in the ASCCP guideline to reduce the risk of cervical cancer progression.

scholarly journals Lead (Pb) exposure from outdoor air pollution: a potential risk factor for cervical intraepithelial neoplasia related to HPV genotypes

2021 ◽  
Author(s):  
Ji Zhang ◽  
Seyed Ali Nazeri ◽  
Amir Sohrabi
Keyword(s):  
Risk Factors ◽  
Cervical Cancer ◽  
Air Pollution ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Progression ◽  
Synergistic Effects ◽  
Intraepithelial Neoplasia ◽  
Outdoor Air ◽  
Outdoor Air Pollution ◽  
Pb Concentration

AbstractHuman papillomavirus genotypes (HPVs) have been confirmed to be the major cause of cervical intraepithelial neoplasia (CIN) that remains to be one of the most common women cancers around the world. It seems other risk factors have synergistic effects on cervical cancer occurrence including smoking, dietary pattern, sexual behavior, ethnicity, epigenetics, and environmental hazardous materials. Our study characterized the potential cancerous role of lead (Pb) as a common toxic environmental pollutant agent on CIN outcomes. Lead concentration was quantified using an atomic absorption spectrometer in liquid-based cytology specimens of 40 CIN-HPV positive subjects, 50 HPV infected non-cancerous cases, and 43 non-HPV infected/non-cancerous women. Pb concentration was 5.5 (4.7–6.4) μg/dL, 4.7 (4.2–8.7) μg/dL, and 4.7 (4.5–5.4) μg/dL in the CIN-HPV positive group, HPV infected non-cancerous cases, and non-HPV infected/non-cancerous group, respectively. The results showed higher Pb concentration is associated with higher risk for cervical malignancy in comparison with non-HPV infected/non-cancerous subjects, after controlling for age effect (aOR = 4.55, 95% CI: 1.55–15.07, P < 0.01). Our finding suggested a direct significant association between Pb accumulation and CIN existence. The consequences need to be further validated by including more relevant risk factors and controlling the confounders for better understating of Pb impact from outdoor air pollution on cervical cancer progression.

PECULIARITIES OF PAPILLOMAVIRUS GENOTYPING IN PATIENTS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA

2020 ◽  
pp. 104-111
Author(s):  
N.A. Shmakova ◽  
G.N. Chistyakova ◽  
I.N. Kononova ◽  
I.I. Remizova
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Viral Load ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Squamous Intraepithelial Lesions ◽  
Hpv 16 ◽  
The World ◽  
Intraepithelial Lesions ◽  
Hpv 18

Recently, there has been a steady growth of cervical cancer all over the world, especially in Russia. Patients with cervical cancer have become much younger. At the same time, the human papillomavirus is not only the main factor in the neoplastic process, but it is also one of the most common sexually transmitted infections in the world. The aim of the paper is to assess the prevalence and characteristics of human papillomavirus genotypes in patients with cervical intraepithelial neoplasia. Materials and Methods. During the periodic screening we examined 213 women of a reproductive age with HPV infection. All patients underwent liquid-based cytology and human papillomavirus genotyping by polymerase chain reaction. Results. We revealed that the prevalence of cervical intraepithelial neoplasia among women with papillomavirus infection was 80.3 % (n=171). According to human papillomavirus genotyping, HPV 16 (38 %) and HPV 33 (32 %) prevailed. We also observed positive high correlation between high-grade squamous intraepithelial lesions (HSIL) and HPV 18 (r=+0.759, p=0.001), a negative mean correlation between HPV 45 and low-grade squamous intraepithelial lesions (LSIL) (r=-0.643, p=0.002). A cohort of patients with severe intraepithelial cervical lesions demonstrated high viral load rates. Conclusion. According to the results obtained, we established the dominance of HPV 16 and HPV 33 genotypes in cervical intraepithelial neoplasia. There were significant differences between HSIL and LSIL patients with HPV 18 and HPV 45. There was also a correlation between an increase in the viral load with the severity of the pathological process. Keywords: human papillomavirus, intraepithelial cervical neoplasms, cervical cancer. В последние годы в мире, особенно в России, наблюдается неуклонный рост и «омолаживание» рака шейки матки. При этом вирус папилломы человека является не только основным фактором прогрессирования неопластического процесса, но и одной из наиболее распространенных инфекций, предаваемых половым путем, в мире. Цель. Оценить распространенность и характеристику генотипов папилломавирусной инфекции у пациенток с цервикальными интраэпителиальными неоплазиями. Материалы и методы. Проведено обследование 213 пациенток репродуктивного возраста с ВПЧ-инфекцией, пришедших на профилактический осмотр. Всем женщинам было выполнено цитологическое исследование жидкостным методом и генотипирование вируса папилломы человека методом полимеразной цепной реакции. Результаты. Распространенность цервикальных интраэпителиальных неоплазий среди женщин с папилломавирусной инфекцией составила 80,3 % (171 пациентка). Согласно данным генотипирования вируса папилломы человека превалировал 16-й (38 %) и 33-й типы (32 %). Выявлена положительная высокая корреляционная связь между цервикальными неоплазиями высокой степени онкогенного риска (HSIL) и 18-м типом ВПЧ-инфекции (r=+0,759 при р=0,001), отрицательная средняя корреляционная связь 45-го типа ВПЧ с низкой степенью онкогенного риска (LSIL) (r=-0,643 при р=0,002). Продемонстрированы высокие показатели вирусной нагрузки в когорте пациенток с тяжелыми внутриэпителиальными цервикальными поражениями. Выводы. По результатам полученных данных установлено доминирование 16-го и 33-го генотипов ВПЧ при цервикальных интраэпителиальных неоплазиях с наличием значимых различий между пациентами с HSIL и LSIL в отношении 18-го и 45-го типов, а также связь роста уровня вирусной нагрузки с увеличением степени тяжести патологического процесса. Ключевые слова: вирус папилломы человека, интраэпителиальные новообразования шейки матки, рак шейки матки.

Long noncoding RNA HOTAIR as a biomarker for the detection of Cervical Cancer and Cervical Intraepithelial Neoplasia

2021 ◽  
Vol 19 (4) ◽  
Author(s):  
Maryame Lamsisi ◽  
Guorong Li ◽  
Mustapha Benhessou ◽  
Mohammed El Mzibri ◽  
Amal Bouziyane ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Intraepithelial Neoplasia

CYP1A1 gene polymorphism as a risk factor for cervical intraepithelial neoplasia and invasive cervical cancer

2006 ◽  
Vol 101 (3) ◽  
pp. 503-506 ◽  
Author(s):  
Cagatay Taskiran ◽  
Dilek Aktas ◽  
Nilufer Yigit-Celik ◽  
Mehmet Alikasifoglu ◽  
Kunter Yuce ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Risk Factor ◽  
Gene Polymorphism ◽  
Cervical Intraepithelial Neoplasia ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Cyp1a1 Gene

Thermal Coagulation Device for Treating Cervical Dysplasia

2018 ◽  
Vol 26 (2) ◽  
pp. 149-152 ◽  
Author(s):  
Ashley Langell ◽  
Timothy Pickett ◽  
Catherine Mangum ◽  
Jennwood Chen ◽  
John Langell
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Resource Constraints ◽  
Low Cost ◽  
Stakeholder Analysis ◽  
Cervical Dysplasia ◽  
Intraepithelial Neoplasia ◽  
Cervical Cancer Prevention ◽  
User Centered Design ◽  
Thermal Coagulation

Background. Cervical cancer remains a leading cause of cancer-related deaths worldwide despite being a highly preventable disease. Nine out of every 10 deaths due to cervical cancer occur in developing regions with limited access to medical care and unique resource constraints. To address cervical cancer prevention within the confines of these unique limitations, our team of students and faculty advisors at the University of Utah’s Center for Medical Innovation developed a low-cost, portable technology that utilizes thermal coagulation, a form of heat ablation, to treat cervical intraepithelial neoplasia. Methods. A multidisciplinary team of students worked with clinical and industry advisors to develop a globally applicable treatment for cervical intraepithelial neoplasia through a systematic process of problem validation, stakeholder analysis, user-centered design, business plan development, and regulatory clearance. Results. Our efforts resulted in the development of a functional, self-contained, battery-operated prototype within 72 days, followed by Food and Drug Administration clearance of a finalized device within 18 months. Conclusion. Interdisciplinary university programs that leverage the capabilities of academic-industry partnerships can accelerate the development and commercialization of affordable medical technologies to solve critical global health issues.

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