miR-9, miR-21, miR-27b, and miR-34a Expression in HPV16/58/52-Infected Cervical Cancer

The aim of this study was to observe the expression of miR-9, miR-21, miR-27b, and miR-34a related with E6/E7 in HPV16-, HPV52-, and HPV58-infected cervical cancer patients and explore their possible role in cervical cancer with HPV infection. The expression levels of 4 miRNAs were detected in cervical exfoliated cells using qRT-PCR. In the current study, miR-34a expression was significantly upregulated in HPV-positive cervical cancer compared with the HPV-negative healthy population and HPV-positive CIN, but just the expression of miR-34a in HPV16 cervical cancer was statistically significant, and the expression of HPV52 and HPV58 was not statistically significant. The expression of miR-21 increased in HPV-positive cervical cancer compared with HPV-positive CIN, but only HPV16-infected cervical cancer had statistical significance compared with HPV16-infected CIN. By observing the change trend of each subtype group, we can show that the expression of miR-9 in HPV16 CIN was opposite to the other subtypes, and it was upregulated, compared with HPV58 CIN, and significantly increased. The level change of miR-27b in HPV58 cervical cancer and HPV58 CIN was opposite to the other subtypes; unlike the expression of miR-27b which was upregulated in HPV16 and HPV52 infected, it was downregulated compared with Normal. We also found that the expression of miR-34a and miR-9 was contrary to other studies. These findings indicate that the upregulated miR-21 expression may be a biomarker to distinguish between CC and CIN. miR-34a in HPV infection, especially in HPV16 infection, might be related to the occurrence and development of cervical cancer. The infection of different subtypes may play different roles in disease by activating different mechanisms; miRNAs play a very complex role in tumorigenesis and development, and there may be multiple targets in which multiple mechanisms play a role.

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The Effect of Productive HPV16 Infection on Global Gene Expression of Cervical Epithelium

10.1101/295402 ◽

2018 ◽

Cited By ~ 1

Author(s):

Sa Do Kang ◽

Sreejata Chatterjee ◽

Samina Alam ◽

Anna C. Salzberg ◽

Janice Milici ◽

...

Keyword(s):

Gene Expression ◽

Cervical Cancer ◽

Immune Response ◽

Early Stage ◽

Therapeutic Targets ◽

Global Gene Expression ◽

Hpv Infection ◽

Cervical Tissue ◽

First Time ◽

Hpv16 Infection

AbstractHuman papillomavirus (HPV) infection is the world’s most common sexually transmitted infection, and is responsible for most cases of cervical cancer. Previous studies of global gene expression changes induced by HPV infection have focused on the cancerous stages of infection, and therefore, not much is known about global gene expression changes at early pre-neoplastic stages of infection. We show for the first time, global gene expression changes of early stage HPV16 infection in cervical tissue using 3-dimensional organotypic raft cultures that produce high levels of progeny virions.cDNA microarray analysis showed that a total of 594 genes were upregulated and 651 genes were downregulated at least 1.5-fold with HPV16 infection. Gene ontology analysis showed that biological processes including cell cycle progression and DNA metabolism were upregulated, while skin development, immune response, and cell death were downregulated with HPV16 infection in cervical keratinocytes. Individual genes were selected for validation at the transcriptional and translational levels including UBC, which was central to the protein association network of immune response genes, and top downregulated genes RPTN, SERPINB4, KRT23, and KLK8. In particular, KLK8 and SERPINB4 have shown to be upregulated in cancer, which contrasts our results.Organotypic raft cultures that allow full progression of the HPV life-cycle have allowed us to identify novel gene modulations and potential therapeutic targets of early stage HPV infection in cervical tissue. Additionally, our results suggest that early stage productive infection and cancerous stages of infection are distinct disease states expressing different transcriptomes.ImportancePersistent HPV infection is responsible for most cases of cervical cancer. Transition from precancerous to cancerous stages of HPV infection is marked by a significant reduction in virus production. Most global gene expression studies of HPV infection have focused on the cancerous stages. Therefore, little is known about global gene expression changes at precancerous stages. For the first time, we measured global gene expression changes at precancerous stages of HPV16 infection in human cervical tissue producing high levels of virus. We identified a group of genes that are typically overexpressed in cancerous stages to be significantly downregulated at the precancerous stage. Moreover, we identified significantly modulated genes that have not yet been studied in the context of HPV infection. Studying the role of these genes in HPV infection will help us understand what drives the transition from precancerous to cancerous stages, and may lead to development of new therapeutic targets.

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Human papillomavirus infection rate, distribution characteristics, and risk of age in pre- and postmenopausal women

BMC Women s Health ◽

10.1186/s12905-021-01217-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yan Shen ◽

Jing Xia ◽

Huihui Li ◽

Yang Xu ◽

Sanping Xu

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

High Risk ◽

Postmenopausal Women ◽

Infection Rate ◽

Hpv Infection ◽

The Other ◽

Distribution Characteristics ◽

Significant Difference ◽

High Risk Hpv

Abstract Background The incidence rate of cervical cancer is increasing yearly. The persistent infection of high-risk human papillomavirus (HPV) is the main factor leading to cervical cancer. HPV infection is double peak type. This study aimed at analyzing the HPV distribution characteristics, infection rate, and risk of age in pre- and postmenopausal women. So as to provide reference for the prevention of HPV infection and cervical cancer screening strategy. Methods A retrospective analysis of 4614 women who underwent cervical cytology, and HPV examination from January 2018 to October 2019 at the healthcare department of Wuhan Union Hospital was done. We explored the characteristics and distribution of HPV infections around the menopause, then comparing the infection rate of HPV in postmenopause and over 65 years old, in order to analyze the influence of different ages on HPV infection. Results Generally, the HPV infection rate was 13.10% (539/4115), whereby the high-risk subtype constituted 73.84% (398/539) of all positive cases. On the other hand, the HPV39 infection was more common in postmenopausal women; however, there was no significant difference in the distribution of the other types in the pre- and postmenopausal women. The first four types were 52/53/58/16. The results further showed that the rates of HPV infection before and after menopause were 12.34% (367/2975) and 15.09% (172/1140), respectively, which had no significant difference (P = 0.056), but more susceptible to high-risk HPV infection after the age of 65 (P = 0.041). Except for 40 years old to menopause, the infection rate of high-risk HPV in this age group was different from that in postmenopause (P = 0.023, 0.729 (0.555, 0.957)), other age groups had no significant effect on high-risk HPV infection. Conclusions It was concluded that whether menopause has nothing to do with HPV infection. Moreover, the risk of high-risk HPV infection in women aged 40 to premenopausal is relatively low, but the infection rate increases after 65. Hence the cutoff screening age should be appropriately prolonged.

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Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

10.21203/rs.2.16632/v2 ◽

2019 ◽

Author(s):

Wei Sun ◽

Xueyun Qin ◽

Jing Zhou ◽

Mingjing Xu ◽

Zhangyan Lyu ◽

...

Keyword(s):

Cervical Cancer ◽

Logistic Regression ◽

Mitochondrial Dna ◽

Copy Number ◽

Wald Test ◽

Hpv Infection ◽

Dna Copy Number ◽

Mitochondrial Dna Copy Number ◽

Exfoliated Cells ◽

Hpv Types

Abstract Background Although human papillomavirus (HPV) infection has been recognized as the major cause of cervical cancer, only a minority of HPV-infected women develop this malignancy. An increasing amount of evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may c ontribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains unknown. Methods In this case-control study, we included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assay s , and logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Interaction between mtCN and HPV types was assessed by using the Wald test in logistic regression models. Results HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls ( P = 0.03). After adjustment for age and HPV types , the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed ( P trend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant. Conclusions Increased mtCN in cervical exfoliated cells is associated with cervical cancer after HPV infection, suggesting a potential role of mtCN in cervical carcinogenesis.

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AB0407 HUMAN PAPILLOMA VIRUS (HPV) INFECTION AND CERVICAL CANCER PREVALENCE IN A PORTUGUESE UNIVERSITY HOSPITAL SINGLE-CENTER SYSTEMIC LUPUS ERYTHEMATOSUS COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5181 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1504.3-1504

Author(s):

J. Sousa Morais ◽

D. G. Oliveira ◽

R. Faria ◽

A. Almeida ◽

M. Brandão ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Cervical Cancer ◽

Human Papillomavirus ◽

Lupus Erythematosus ◽

Hpv Infection ◽

University Hospital ◽

Healthy Population ◽

Single Center ◽

Systemic Lupus ◽

Patient Cohort

Background:About 12% of women worldwide are infected with Human Papillomavirus (HPV), the most frequent cause of cervical cancer (CC) - very prevalent (~ 7,5%) and preventable. National screening efforts are in use in several countries, including Portugal. Patients with Systemic Lupus Erythematosus (SLE) are at increased risk of HPV infection and CC when compared to the healthy population.Objectives:To evaluate the prevalence of HPV infection and rate of incidence of cervical neoplastic lesions in a SLE patient cohort followed at a university hospital.Methods:Retrospective single-center (35 year long, 463 SLE patient cohort) review of all female SLE patients’ local and online national health care records on HPV vaccination and CC screening.Results:Of the 463 SLE patients, 420 were women (91%), of which 322 had records on of HPV infection or CC developed. Mean patients’ current age was 48 years and all had screening for cervical pathology in the last 3 years. Thirty-three patients (11%) had HPV infection diagnosed at a mean age of 44 years. Twenty-seven (8%) of SLE patients were vaccinated for HPV: 8 (22%) of the infected patients had the vaccine, half after the HPV infection. Despite HPV infection, 49 patients (15%) had developed some cervical lesion, of which 41 (84% of cervical lesion) were suggestive of malignancy, and ultimately CC was diagnosed in 20 women (41%; 6% of total women), with a mean age at diagnosis of 45 years. All CC patients had history of HPV infection, but only 3 women (15%; 0,9% of total women) had been vaccinated against HPV, 2 after the diagnoses of CC and 1 before.Conclusion:In our population the prevalence of HPV was higher than reported for the general population using the World Health Organization database, conforming the higher risk of HPV infection in SLE patients. The prevalence of cervical cancer, however, was similar to the healthy population.References:[1]https://www.who.int/immunization/diseases/hpv/en/[2]Forman David (2012); “Global Burden of Human Papillomavirus and Related Diseases”, Vaccine, Elsevier Volume 30, Supplement 5, 20 November 2012[3]Grein Ingrid (2016), Department of Pediatric Immunology and Rheumatology, Netherland (2016), HPV infection and vaccination in Systemic Lupus Erythematosus patients: what we really should know, Pediatric Rheumatology, 2016Disclosure of Interests: :None declared

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HPVE6/E7,hTERT, andKi67mRNA RT-qPCR Assay for Detecting High-Grade Cervical Lesion with Microscope Slides

Analytical Cellular Pathology ◽

10.1155/2019/9365654 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7

Author(s):

Geehyuk Kim ◽

Jemberu Taye ◽

Kwangmin Yu ◽

Sunyoung Park ◽

Jungho Kim ◽

...

Keyword(s):

Cervical Cancer ◽

Precancerous Lesion ◽

Hpv Infection ◽

Screening Methods ◽

High Grade ◽

Human Telomerase Reverse Transcriptase ◽

Exfoliated Cells ◽

Hpv Test ◽

Hpv Screening ◽

Microscope Slides

After breast and colon cancer, cervical cancer is the third most common cancer of women worldwide. Since human papillomavirus (HPV) infection is known to be the predominant cause of cervical cancer, molecular HPV screening is currently used along with cytological and histological examination methods for precancer diagnosis. Nevertheless, the sensitivity of the current HPV test is less than 80%; thus, many cervical cancer cases are not able to be diagnosed by HPV screening alone, and likewise, patients with cervical cancer are often determined to be HPV-negative by the current screening methods. Therefore, human telomerase reverse transcriptase (hTERT) andKi67previously identified as cancer markers were attempted. And cervical exfoliated cells of high-grade squamous intraepithelial lesion (HSIL), the most severe precancerous lesion of cancer, were used in the study. However, it takes a long time to collect enough specimens to conduct statistical analysis. Therefore, in the present study, microscope slides, cervical exfoliated cells on glass slides, were attempted. The results of the analysis demonstrated thathTERTandKi67expression levels were useful in distinguishing between cancerous and normal specimens, exhibiting a higher sensitivity and specificity than conventional HPVE6/E7testing. And the study suggests clinical slide cell samples could be effectively used in the context of retrospective studies to identify novel biomarkers.

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Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

10.21203/rs.2.16632/v4 ◽

2020 ◽

Author(s):

Wei Sun ◽

Xueyun Qin ◽

Jing Zhou ◽

Mingjing Xu ◽

Zhangyan Lyu ◽

...

Keyword(s):

Cervical Cancer ◽

Logistic Regression ◽

Mitochondrial Dna ◽

Copy Number ◽

Wald Test ◽

Hpv Infection ◽

Dna Copy Number ◽

Mitochondrial Dna Copy Number ◽

Exfoliated Cells ◽

Hpv Types

Abstract Background: Although human papillomavirus (HPV) infection has been recognized as the cause of cervical cancer in over 99% of cases, only a minority of HPV-infected women develop this malignancy. Emerging evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may contribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains unknown.Methods: In this case-control study, we included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assays, and logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Interaction between mtCN and HPV types was assessed by using the Wald test in logistic regression models.Results: HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls (1.63 vs. 1.23, P = 0.03). After adjustment for age and HPV types, the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed (Ptrend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant.Conclusions: In women who test HPV positive, the increase of mtCN in cervical exfoliated cells is associated with cervical cancer. This suggests a potential role of mtCN in cervical carcinogenesis.

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Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

10.21203/rs.2.16632/v5 ◽

2020 ◽

Author(s):

Wei Sun ◽

Xueyun Qin ◽

Jing Zhou ◽

Mingjing Xu ◽

Zhangyan Lyu ◽

...

Keyword(s):

Cervical Cancer ◽

Logistic Regression ◽

Mitochondrial Dna ◽

Copy Number ◽

Wald Test ◽

Hpv Infection ◽

Dna Copy Number ◽

Mitochondrial Dna Copy Number ◽

Exfoliated Cells ◽

Hpv Types

Abstract Background Although human papillomavirus (HPV) infection has been recognized as the cause of cervical cancer in over 99% of cases, only a minority of HPV-infected women develop this malignancy. Emerging evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may contribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains unknown.Methods In this case-control study, we included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assays, and logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Interaction between mtCN and HPV types was assessed by using the Wald test in logistic regression models.Results HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls (1.63 vs. 1.23, P = 0.03). After adjustment for age and HPV types, the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed (Ptrend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant.Conclusions In women who test HPV positive, the increase of mtCN in cervical exfoliated cells is associated with cervical cancer. This suggests a potential role of mtCN in cervical carcinogenesis.

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P–578 Human pappiloma virus 16,18 genome methylation patterns in subfertile women

Human Reproduction ◽

10.1093/humrep/deab130.577 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

E Mastora ◽

A Zikopoulos ◽

A Galani ◽

I Georgiou ◽

K Zikopoulos

Keyword(s):

Cervical Cancer ◽

Dna Methylation ◽

High Risk ◽

Cervical Intraepithelial Neoplasia ◽

Promoter Region ◽

Methylation Status ◽

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Hpv Types ◽

Hpv16 Infection

Abstract Study question A comparison between L1 gene and LCR region methylation status of HPV16 and HPV18 viruses in subfertile women, investigating HPV methylation pattern in cervical cancer and asymptomatic HPV infection. Summary answer CpG methylation was more frequent in L1 gene compared to LCR in both HPV types. Methylation levels were associated with the grade of cervical dysplasia. What is known already HPV infection is a common sexually transmitted disease, related to genital warts and cancer. DNA methylation as a dynamic and strictly controlled process can be involved in numerous cellular processes, cell differentiation, gene expression regulation and genome reprogramming. Human pappiloma virus genome epigenetic alterations may play a key role in HPV life cycle as well as in the oncogenic process in general. However, whether the prevalence of high risk HPV is correlated with female infertility, has yet to be elucidated. Study design, size, duration From January 2015 to December 2019, about 2505 infertile couples were referred to the Human Reproduction Unit of Ioannina University Hospital. A total of 212 clinical and laboratory data from female partners were included in the study. Participants/materials, setting, methods Cervical smears were studied for HPV DNA methylation. CpG methylation was compared among L1 gene and LCR region in both HPV types. A bisulfite modification assay followed by DNA amplification and sequencing was performed to analyse HPV16 and HPV18 genome. Main results and the role of chance In HPV16 types, L1 gene and promoter region indicated high methylation levels in cervical cancer cases. LCR regions methylation levels ranged from 0,5% to 24,2% in asymptomatic HPV16 infection or cervical intraepithelial neoplasia and cervical cancer, respectively. As for L1 gene, the differences between asymptomatic HPV16 infection and cervical cancer cases were statistically significant (P = 0.003). In HPV18 types, L1 gene was methylated in cervical intraepithelial neoplasia and cervical cancer cases. Promoter region methylation levels were high in cervical cancer cases while LCR region methylation levels were low. Limitations, reasons for caution Main limitation is the relatively small size of the collected samples. Wider implications of the findings: HPV genome investigation, as for methylation status, may lead to better understanding and earlier diagnostics of cervical pathology in infertile population. These observations point out the importance of fertility preservation in women at high risk for cervical neoplasia. Trial registration number Not applicable

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Knowledge of Human Papillomavirus and Uptake of its Vaccine among Female Undergraduate Students of Ambrose Alli University, Ekpoma, Nigeria

Journal of Community Medicine and Primary Health Care ◽

10.4314/jcmphc.v33i1.6 ◽

2021 ◽

Vol 33 (1) ◽

pp. 64-75

Author(s):

A.R. Isara ◽

N. Osayi

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Undergraduate Students ◽

Hpv Vaccine ◽

Sexual Debut ◽

Statistical Significance ◽

Hpv Infection ◽

Vaccine Uptake ◽

P Value ◽

Female Undergraduate

Background: Human Papillomavirus (HPV) is a prerequisite for the development of cervical cancer which is the fourth most common cancer affecting women worldwide. The use of HPV vaccine has been found to be responsible for significant decline in the prevalence of HPV infection and consequently, of cervical cancer. This study assessed the knowledge of HPV and the uptake of HPV vaccine among female undergraduate students of Ambrose Alli University, Ekpoma, Nigeria.Methods: This institution-based cross-sectional study was carried out among 229 students selected using multi-staged sampling technique. A structured, pretested, self-administered questionnaire was used to collect data. IBM SPSS version 21.0 was used for data analysis. Statistical significance was set at p-value less than 0.05.Results: Only 12 (5.2%) students were knowledgeable about HPV and 39 (17.0%) were aware of the existence of HPV vaccines. The participants’ age (p = 0.031) and level of study (p = 0.026) were significantly associated with knowledge of HPV. Only 1 (0.44%) student had received the vaccine. Eight (10.8%) students had their sexual debut at 10 to 14 years, 9 (12.1%) had more than five sexual partners and 21 (23.4%) never used condom during sexual intercourse.Conclusion: The knowledge about HPV infection and uptake of HPV vaccine were very low in this study. Concerted effort should be made by health authorities to create awareness about HPV infection and its vaccine among university students. This will improve HPV vaccine uptake, prevent HPV infections and reduce the prevalence of cervical cancer.

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miR-508-5p and mir-510-5p expressions and their relationships with spermatozoa motility and morphology

Journal of Shahrekord University of Medical Sciences ◽

10.34172/jsums.2020.23 ◽

2020 ◽

Vol 22 (3) ◽

pp. 146-150

Author(s):

Tahere Hasheminiya ◽

Mohammadreza Saberiyan ◽

Delnya Gholami ◽

Hossein Teimori

Keyword(s):

Male Infertility ◽

Statistical Significance ◽

The Other ◽

Quantitative Real Time Pcr ◽

Clinical Criteria ◽

Spermatozoa Motility ◽

Qrt Pcr ◽

Regulatory Functions ◽

Role Of It

Background and aims:miRNAs have regulatory functions in developmental processes. The stages of spermatogenesis can also be affected by miRNAs. We tried to detect a relationship between the expression of miR-508-5p and miR-510-5p and male infertility. The purpose of this study was to investigate the association between expression of miR-508-5p and mir-510-5p in ejaculated sperm from patients with idiopathic asthenozoospermia, teratozoospermia, and teratoasthenozoospermia. Materials and Methods:We enrolled 18 men with asthenozoospermia, 17 men with teratozoospermia, 18 men with teratoasthenozoospermia, and 18 individuals with normozoospermia based on the clinical criteria. Then, the expressions of the mentioned miRs in the spermatozoa were evaluated by quantitative real-time PCR (qRT-PCR). Kruskal-Wallis was used to compare their expressions in the studied groups. Results: The expression of mir-508-5p did not show any statistical significance in all groups. On the other hand, the expression of miR-510- 5p in teratozoospermia groups (P<0.05) and the asthenozoospermia group (P<0.05) demonstrated a significant downregulation compared with the control and teratoasthenozoospermia groups. Conclusion: By analyzing the expression profile of miRNAs, we concluded that the expression level of miR-510-5p changed in patients with abnormal motility and morphology of spermatozoa; therefore, it may affect infertility by down-regulating the expression of mir-510-5p which shows the role of it in abnormal morphology and motility defects in infertility cases.

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