scholarly journals Cervical Cancer, Papillomavirus, and miRNA Dysfunction

2021 ◽  
Vol 8 ◽  
Author(s):  
Evelyn Gabriela Bañuelos-Villegas ◽  
María Fernanda Pérez-yPérez ◽  
Luis Marat Alvarez-Salas
Keyword(s):  
Cervical Cancer ◽  
Human Cancer ◽  
Precancerous Lesions ◽  
Invasive Disease ◽  
Hpv Infection ◽  
Infection Process ◽  
Cervical Carcinogenesis ◽  
Regulate Gene Expression ◽  
Hpv Types ◽  
Cervical Tumors

Cervical cancer is the leading cause of death by cancer in women from developing countries. Persistent infection with high-risk human papillomavirus (HPV) types 16 and 18 is a major risk factor for cervical carcinogenesis. Nevertheless, only a few women with morphologic expression of HPV infection progress into invasive disease suggesting the involvement of other factors in cervical carcinogenesis. MicroRNAs (miRNAs) are conserved small non-coding RNAs that negatively regulate gene expression including genes involved in fundamental biological processes and human cancer. Dysregulation of miRNAs has been widely reported in cervical cancer. This work focuses on reviewing the miRNAs affected during the HPV infection process, as well relevant miRNAs that contribute to the development and maintenance of malignant cervical tumor cells. Finally, we recapitulate on miRNAs that may be used to distinguish between healthy individuals from patients with precancerous lesions or cervical tumors.

scholarly journals FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Luhan Zhang ◽  
Hong Yu ◽  
Tian Deng ◽  
Li Ling ◽  
Juan Wen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Precancerous Lesions ◽  
Expression Profiles ◽  
Precancerous Lesion ◽  
Disease Free Survival ◽  
Hpv Infection ◽  
Cervical Carcinogenesis ◽  
Normal Epithelium ◽  
Key Genes

Human papillomavirus (HPV)-mediated cervical carcinogenesis is a multistep progressing from persistent infection, precancerous lesion to cervical cancer (CCa). Although molecular alterations driven by viral oncoproteins are necessary in cervical carcinogenesis, the key regulators behind the multistep process remain not well understood. It is pivotal to identify the key genes involved in the process for early diagnosis and treatment of this disease. Here we analyzed the mRNA expression profiles in cervical samples including normal, cervical intraepithelial neoplasia (CIN), and CCa. A co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to reveal the crucial modules in the dynamic process from HPV infection to CCa development. Furthermore, the differentially expressed genes (DEGs) that could distinguish all stages of progression of CCa were screened. The key genes involved in HPV-CCa were identified. It was found that the genes involved in DNA replication/repair and cell cycle were upregulated in CIN compared with normal control, and sustained in CCa, accompanied by substantial metabolic shifts. We found that upregulated fibronectin type III domain-containing 3B (FNDC3B) and downregulated bisphosphoglycerate mutase (BPGM) could differentiate all stages of CCa progression. In patients with CCa, a higher expression of FNDC3B or lower expression of BPGM was closely correlated with a shorter overall survival (OS) and disease-free survival (DFS). A receiver operating characteristic (ROC) analysis of CIN and CCa showed that FNDC3B had the highest sensitivity and specificity for predicting CCa development. Taken together, the current data showed that FNDC3B and BPGM were key genes involved in HPV-mediated transformation from normal epithelium to precancerous lesions and CCa.

The role of programmed cell death ligand-1/ programmed cell death-1 (PD-L1/PD-1) in HPV-induced cervical cancer and potential for their use in blockade therapy

2020 ◽  
Vol 27 ◽  
Author(s):  
Lifang Zhang ◽  
Yu Zhao ◽  
Quanmei Tu ◽  
Xiangyang Xue ◽  
Xueqiong Zhu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Escape ◽  
Hypoxia Inducible Factor ◽  
Hpv Infection ◽  
Advanced Cervical Cancer ◽  
Cervical Carcinogenesis ◽  
Programmed Cell Death 1

Background: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. Methods: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies. Results: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signaling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and MicroRNAs, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in immune escape of cervical cancer through inhibition of host immune response. creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PD-L1/PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment. Conclusion: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body’s immune system to fight the cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.

scholarly journals The application of CRISPR/Cas9 system in cervical carcinogenesis

2021 ◽  
Author(s):  
Chun Gao ◽  
Ping Wu ◽  
Lan Yu ◽  
Liting Liu ◽  
Hong Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Transgenic Mice ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Precancerous Lesions ◽  
Cancer Cell Lines ◽  
Cervical Carcinogenesis ◽  
Cervical Precancerous Lesions

AbstractIntegration of high-risk HPV genomes into cellular chromatin has been confirmed to promote cervical carcinogenesis, with HPV16 being the most prevalent high-risk type. Herein, we evaluated the therapeutic effect of the CRISPR/Cas9 system in cervical carcinogenesis, especially for cervical precancerous lesions. In cervical cancer/pre-cancer cell lines, we transfected the HPV16 E7 targeted CRISPR/Cas9, TALEN, ZFN plasmids, respectively. Compared to previous established ZFN and TALEN systems, CRISPR/Cas9 has shown comparable efficiency and specificity in inhibiting cell growth and colony formation and inducing apoptosis in cervical cancer/pre-cancer cell lines, which seemed to be more pronounced in the S12 cell line derived from the low-grade cervical lesion. Furthermore, in xenograft formation assays, CRISPR/Cas9 inhibited tumor formation of the S12 cell line in vivo and affected the corresponding protein expression. In the K14-HPV16 transgenic mice model of HPV-driven spontaneous cervical carcinogenesis, cervical application of CRISPR/Cas9 treatment caused mutations of the E7 gene and restored the expression of RB, E2F1, and CDK2, thereby reversing the cervical carcinogenesis phenotype. In this study, we have demonstrated that CRISPR/Cas9 targeting HPV16 E7 could effectively revert the HPV-related cervical carcinogenesis in vitro, as well as in K14-HPV16 transgenic mice, which has shown great potential in clinical treatment for cervical precancerous lesions.

scholarly journals Genetic Polymorphism of Cancer Susceptibility Genes and HPV Infection in Cervical Carcinogenesis

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Osamu Nunobiki ◽  
Masatsugu Ueda ◽  
Eisaku Toji ◽  
Michiko Yamamoto ◽  
Kyoko Akashi ◽  
...  
Keyword(s):  
Cancer Susceptibility ◽  
Association Studies ◽  
Gene Promoter ◽  
Hpv Infection ◽  
Host Susceptibility ◽  
Cervical Carcinogenesis ◽  
Mdm2 Gene ◽  
P53 Codon 72 ◽  
Cancer Susceptibility Genes ◽  
Hpv Types

It is widely accepted that specific human papillomavirus (HPV) types are the central etiologic agent of cervical carcinogenesis. However, a number of infected women do not develop invasive lesions, suggesting that other environmental and host factors may play decisive roles in the persistence of HPV infection and further malignant conversion of cervical epithelium. Although many previous reports have focused on HPV and environmental factors, the role of host susceptibility to cervical carcinogenesis is largely unknown. Here, we review the findings of genetic association studies in cervical carcinogenesis with special reference to polymorphisms of glutathione-S-transferase (GST) isoforms, p53 codon 72, murine double-minute 2 homolog (MDM2) gene promoter 309, and FAS gene promoter -670 together with HPV types including our recent research results.

scholarly journals Characteristics of Human Papillomavirus Infection Among Women With Cervical Cytological Abnormalities in the Zhoupu District, Shanghai City, China, 2014–2019

2020 ◽  
Author(s):  
Ping Li ◽  
Qing Liu ◽  
Wei Li ◽  
Zhou Liu ◽  
Baoling Xing ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Precancerous Lesions ◽  
Hpv Infection ◽  
Single Type ◽  
Squamous Intraepithelial Lesions ◽  
Shanghai City ◽  
Intraepithelial Lesions ◽  
Type Infection ◽  
Multiple Type

Abstract Background: Human papillomavirus (HPV) infection is the main cause of precancerous lesions and cervical cancer in women. To determine the epidemiological characteristics as well as the relationship between the HPV genotype and cytology test results among women, we retrospectively collected and analyzed the data from Zhoupu District hospital in Shanghai, China.Methods: We made a retrospective analysis of human papillomavirus prevalence rate of 23,724 women between 2014 and 2019 in the District Zhoupu of Shanghai City in China. Their cervical exfoliations were collected. HPV genotype testing was performed using a commercial kit designed to detect 21 HPV subtypes including 15 high-risk HPV subtypes(16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 ,68) and 6 low-risk HPV subtypes(6, 11, 42, 43, 44 and 81). And the thinPrep cytological test (TCT) was also performed at the same time.Results: Among all 23,724 cases, 3,816 (16.08%) women were infected with HPV. HPV52 (3.19%), HPV58 (2.47%) and HPV16 (2.34%) had higher prevalence. 3,480(91.20%) single-type infections were more common than 336(8.8%) multiple-type infections. Single-type infection was more frequently seen in women aged 50–60 years (16.63%) and <30 years (15.37%), and multiple-type infection was more common in those aged >= 60 (2.67%). Significant differences in secular trends from 2014 to 2019 were observed for subtypes HPV52, 58 and 16.HPV positive rates of women changed significantly along with the time period from 2014 to 2019.Among 4,502 TCT positive women, 15 (4.04%), 125 (2.64%) ,159 (1.54%), 4,202(17.71%) and 1(0.004%) had atypical squamous cells (ASC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), atypical glandular cells (AGC) and cervical adenocarcinoma respectively. The HPV infection rates were 66.08%, 63.99%, 115.20%, 119.50%, and 31.72% for NILM, AGCs, HSILs LSILs and ASCs, respectively.Conclusions: HPV and TCT screening were a key step in the secondary prevention of cervical cancer. Further tracking the results of HPV and TCT was an important clinical strategy for the treatment of cervical precancerous lesions. The widespread use of preventive HPV vaccines can significantly reduce the incidence of pre-neoplastic and neoplastic cervical lesions.

scholarly journals Distribution and Prevalence of High-Risk Human Papillomavirus Genotypes in Cervical Specimens

2020 ◽  
Vol 25 (3) ◽  
pp. 325-331
Author(s):  
Erkan Özmen ◽  
Ülkü Altoparlak ◽  
Muhammet Hamidullah Uyanık ◽  
Abdulkadir Gülen
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Age Groups ◽  
Hpv Infection ◽  
High Rate ◽  
Genotype Distribution ◽  
Hpv Dna ◽  
Hpv Test ◽  
Significant Difference ◽  
Hpv Types

Introduction: Human papillomavirus (HPV) is frequently a sexually transmitted virus and can cause cervical cancer in women. Cervical cancer is the second most common type of cancer among the developing countries. In this study, cervical HPV DNA positivity and genotype distributions were investigated in female patients living in our region and the results were compared with different studies. Materials and Methods: Between 1 July, 2017 and 1 March, 2019, 433 cervical swabs were sent to Ataturk University, Medical Faculty Hospital, Medical Microbiology Laboratory due to suspicion of HPV. Swab samples were evaluated for HPV virus using molecular (Polymerase Chain Reaction-PCR) methods. For this purpose, Xpert HPV Test (Cepheid, Inc, Sunnyvale, CA) was used to identify HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 t in a single sample. Results: Mean age of the patients ranged from 20 to 69 years, with a mean of 39.8 years (± 10.0). Positivity was detected in 62 of the 433 patients. Mean age of the positive patients was 40.2 years (± 11.3). When the positive patients were examined in terms of HPV types, the presence of HPV 16 was observed with a rate of 25.6%, while the HPV 18/45 types were found to be 9.0% in total. When patients were evaluated according to age groups, HPV DNA positivity was highest in the 25-34 age group with 38.7%. In our statistical study, there was no significant difference in HPV DNA positivity rate between the ages of 35 and under 35 years. Conclusion: This study demonstrates the prevalence and viral genotype distribution of HPV infection in women in Erzurum region. HPV type 16 is seen with a high rate in our region.

Human papillomavirus vaccination: evidence base for efficacy and safety

GYNECOLOGY ◽  
2021 ◽  
Vol 23 (2) ◽  
pp. 125-130
Author(s):  
Yuliya E. Dobrokhotova ◽  
Ekaterina I. Borovkova
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Hpv Vaccination ◽  
Intraepithelial Neoplasia ◽  
Evidence Base ◽  
Hpv Infection ◽  
Efficacy And Safety ◽  
Human Papillomavirus Vaccination ◽  
Hpv Types ◽  
Further Development

The article provides a literature review on the prevention of cervical cancer by human papillomavirus (HPV) vaccination. Currently, 3 vaccines are available: the 4-valent vaccine against HPV types 6, 11, 16 and 18, the 9-valent vaccine against HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58 and the bivalent vaccine against HPV types 16 and 18. Vaccination provides protection for women and men against infection with HPV and further development of HPV-associated diseases. Following immunization, seroconversion develops in 93-100% of women and in 99-100% of men and is effective in preventing incident and persistent HPV infection as well as cervical intraepithelial neoplasia. HPV immunization is ineffective in treating an existing HPV infection, genital warts, or anogenital intraepithelial neoplasia. HPV vaccination status does not affect recommendations for cervical cancer screening.

scholarly journals Associations among Serum Lipocalin-2 Concentration, Human Papilloma Virus, and Clinical Stage of Cervical Cancer

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 229 ◽  
Author(s):  
Agnė Vitkauskaitė ◽  
Joana Celiešiūtė ◽  
Saulius Paškauskas ◽  
Erika Skrodenienė ◽  
Rūta Jolanta Nadišauskienė ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papilloma Virus ◽  
Clinical Stage ◽  
Stage Iv ◽  
Hpv Infection ◽  
Control Group ◽  
Lipocalin 2 ◽  
Papilloma Virus ◽  
Tissue Biopsy ◽  
Hpv Types

Background and objective: Lipocalin 2 (LCN2) has an oncogenic role in promoting tumorigenesis through enhancing tumor cell proliferation and the metastatic potential. The aim of our study was to determine whether serum LCN2 could serve as a diagnostic marker of cervical cancer (CC) and to evaluate the correlation between its serum concentration, the clinical stage of the cancer and Human Papilloma Virus HPV infections in women. Materials and methods: A total of 33 women with histologically proven cervical cancer (CC), 9 women with high- grade cervical intraepithelial neoplasia (HSIL) and 48 healthy women (NILM) were involved in the study. A concentration of LCN2 was assayed with the Magnetic LuminexR Assay multiplex kit. An HPV genotyping kit was used for the detection and differentiation of 15 high-risk (HR) HPV types in the liquid-based cytology medium (LBCM) and the tissue biopsy. Results: The majority (84.8%) of the women were infected by HPV16 in the CC group, and there was no woman with HPV16 in the control group (P < 0.01). Several types of HR HPV were found more often in the LBCM compared to in the tissue biopsy (P = 0.044). HPV16 was more frequently detected in the tissue biopsy than the LBCM (P < 0.05). The LCN2 level was higher in HPV-positive than in HPV-negative women (P = 0.029). The LCN2 concentration was significantly higher in women with stage IV than those with stage I CC (P = 0.021). Conclusions: Many HR HPV types, together with HPV16/18, can colonize the vagina and cervix, but often HPV16 alone penetrates into the tissue and causes CC. The serum LCN2 concentration was found to be associated not only with HR HPV infection, irrespective of the degree of cervical intraepithelial changes, but also with advanced clinical CC stage. LCN2 could be used to identify patients with advanced disease, who require a more aggressive treatment.

Association of detection of aflatoxin in plasma of Kenyan women with increased detection of oncogenic HPV.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5530-5530
Author(s):  
Jianjun Zhiang ◽  
Elkanah Omenge ◽  
Titus Maina ◽  
Kapten Muthoka ◽  
Stephen Kiptoo ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cervical Dysplasia ◽  
Hpv Infection ◽  
Immunosuppressive Agent ◽  
Sub Saharan Africa ◽  
Hpv Testing ◽  
Hpv 16 ◽  
Kenyan Women ◽  
Hpv Types ◽  
Oncogenic Hpv

5530 Background: Cervical cancer is the leading cause of cancer-related deaths among women living in Africa. Only a small proportion of HPV-infected women develop cervical cancer and other cofactors may increase a woman’s risk of developing cervical cancer. Aflatoxin, a potent carcinogen and immunosuppressive agent, is produced by fungi that contaminate corn and other staple foods in sub-Saharan Africa. Women who ingest aflatoxin may be more likely to have persistent infections with oncogenic HPV type. Methods: Demographics, behavioral data, plasma, and cervical swabs were collected from HIV-uninfected women 18 and 45 years of age who presented for cervical cancer screening at Moi Referral and Teaching Hospital (Eldoret, Kenya) and had normal VIA examination. HPV testing was performed on cervical swabs using the Roche Linear Array Assay. Aflatoxin-albumin adduct (AFB1-lys) was detected and quantified in plasma. The association of plasma AFB1-lys detection and concentration and the detection of HPV was examined. Results: Sufficient plasma was available from 88 HIV-uninfected women and was transported to the U.S. for aflatoxin testing. Valid HPV testing results were available for 86 of these women (mean age 34.0 years); 49 women (57.0%) had detectable AFB1-lys and 37 (43.0%) had no detection. Substantial variation existed in plasma AFB1-lys concentrations among the 49 women (range 0.02 to 0.21 pg/µL). Detection of AFB1-lys was not associated with age, and other behavioral factors such as number of lifetime partners, marital status and age at first sex. AFB1-lys detection was associated with detection of A9 HPV types (HPV 16, 31, 33, 35, 52, and 58) as a group in cervical swabs (p = 0.029) as well as A9 types excluding HPV 16 (p = 0.020), but not with individual A9 types, A7 HPV types (such as HPV 18), or low-risk HPV types. A concentration dependent association of AFB1-lys was seen with detection of A9 HPV types as a group (p = 0.009), non-HPV 16 A9 types (p = 0.005), and HPV 52 (p = 0.042), but not with the A7 HPV types. Conclusions: AFB1-lys was detected in 57% of HIV-uninfected Kenyan women without cervical dysplasia. AFB1-lys-positive women were more likely than AFB1-lys-negative women to have oncogenic HPV A9 types detected. Higher plasma AFB1-lys concentrations were associated with increased likelihood of oncogenic HPV A9 type detection. Further studies are needed to determine if chronic exposure to aflatoxin interacts with HPV infection (and possibly HIV co-infection) to modulate the risk of cervical cancer in women in Kenya and other developing countries.

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