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PloS One 2024Colorectal cancer (CRC) is a cancer type that is thought to be influenced by human papillomaviruses (HPVs) and human polyomaviruses (HPyVs). In Egypt, CRC ranks as the...
BACKGROUND
Colorectal cancer (CRC) is a cancer type that is thought to be influenced by human papillomaviruses (HPVs) and human polyomaviruses (HPyVs). In Egypt, CRC ranks as the 7th most common cancer, accounting for 3.47% of male cancers and 3% of female cancers. However, there is currently a lack of information regarding the presence of PyVs and HPVs co-infection specifically in CRC cases in Egypt. Therefore, the aim of this study was to investigate the occurrence of HPVs and HPyVs (JCPyV, BKPyV, and SV40) infections, as well as co-infections, among CRC patients in Egypt. Additionally, the study aimed to assess any potential association between these viral infections and tumor stages.
METHODS
In the present study, we analyzed a total of 51 tissue samples obtained from Egyptian CRC patients, along with 19 polyps' samples. Our investigation focused on the detection and genotyping of HPyVs using Real-Time PCR. Additionally, we employed real-time PCR for the detection of HPVs, and for their genotyping, we utilized a combination of PCR amplification followed by sequencing.
RESULTS
In our study, we found evidence of HPyVs infection in the CRC patients, specifically SV40 (25.5%) and BKPyV (19.6%). However, JCPyV was not detected in the samples that were examined. Additionally, we discovered that HPV was present in 43.1% of the CRC patients. When considering viral co-infections, 19.6% of the CRC samples showed coexistence of multiple viruses, while no co-infections were found in the polyps samples. Importantly, we observed a significant correlation between the presence of HPVs and advanced colorectal tumor grades B2 and D.
CONCLUSION
Our findings provide valuable data for the detection of oncogenic viruses in colorectal cancer (CRC) and underscore the association of viral co-infections with advanced tumor stages. However, further research with larger cohorts is necessary to validate these findings and strengthen their significance in the field of CRC.
Topics: Humans; Colorectal Neoplasms; Egypt; Female; Male; Middle Aged; Polyomavirus Infections; Papillomavirus Infections; Polyomavirus; Papillomaviridae; Case-Control Studies; Coinfection; Aged; Adult; Tumor Virus Infections; Genotype
PubMed: 38861564
DOI: 10.1371/journal.pone.0304147 -
PloS One 2024Advances in laboratory techniques for HPV diagnosis necessitate a thorough assessment of the efficiency, replicability, sensitivity, and specificity of those methods.... (Comparative Study)
Comparative Study
Comparative evaluation of HPV genotyping: A study on the performance concordance between Anyplex II HPV28 detection and Linear Array genotyping tests in nationwide studies in Brazil.
BACKGROUND
Advances in laboratory techniques for HPV diagnosis necessitate a thorough assessment of the efficiency, replicability, sensitivity, and specificity of those methods. This study aims to validate and compare HPV detection/genotyping using the Anyplex™ II HPV28 Detection assay (Seegene) assay and the Linear Array HPV Genotyping test (Roche Diagnostics) on genital samples for use in epidemiological studies.
METHODS
From 6,388 penile and cervical DNA samples collected in the POP-Brazil, 1,745 were randomly selected to be included in this study. The samples were submitted to HPV detection and genotyping following the manufacturers' protocols. DNA was genotyped using the Anyplex™ II HPV28 Detection kit (Seegene), and the results were compared to those obtained using the Linear Array HPV Genotyping test (Roche Diagnostics). Concordance of HPV genotyping results was assessed by the percentage agreement and Cohen's kappa score (κ).
RESULTS
The agreement between the two methodologies was deemed good for HPV detection (κ = 0.78). Notably, Anyplex™ II HPV28 demonstrated enhanced capability in detecting a broader spectrum of genotypes compared to Linear Array.
CONCLUSION
Anyplex™ II HPV28 exhibited comparable results to the Linear Array assay in clinical specimens, showcasing its potential suitability for a diverse array of research applications requiring the detection and genotyping of HPV. The study supports the utility of Anyplex™ II HPV28 as an effective tool for HPV screening in epidemiological studies, emphasizing its robust performance in comparison to established diagnostic tests.
Topics: Humans; Brazil; Papillomavirus Infections; Female; Genotyping Techniques; Male; Papillomaviridae; Genotype; DNA, Viral; Adult; Middle Aged; Sensitivity and Specificity; Alphapapillomavirus
PubMed: 38861542
DOI: 10.1371/journal.pone.0305122 -
Journal of Obstetrics and Gynaecology :... Dec 2024The vaginal flora has been reported to be associated with human papillomavirus (HPV) infection. The purpose of this study was to investigate the characteristics of the...
OBJECTIVE
The vaginal flora has been reported to be associated with human papillomavirus (HPV) infection. The purpose of this study was to investigate the characteristics of the cervical microbiota in patients with HPV infection and to analyse the changes in the vaginal flora and enzyme profiles in females with HPV infection.
METHODS
We conducted a cross-sectional study involving 206 participants who underwent HPV genotyping, sexually transmitted diseases pathogen testing, cytology examination, and microbiome analysis. Additionally, we collected 115 HPV-negative samples and 48 HPV-positive samples for 16S rRNA amplicon sequencing. The vaginal microbial communities of both groups were analysed for diversity and differences to explore their association with HPV infection.
RESULTS
The abundance of was found to be reduced, while was significantly more prevalent in the HPV + group. In terms of alpha diversity indices, the Shannon index ( = .0036) and Simpson index ( = .02) were higher in the HPV + group compared to the HPV - group, indicating greater community diversity in the HPV + group. Among the 10 sexually transmitted diseases pathogens analysed, Uup3 and Uup6 were significantly associated with HPV infection. Statistically significant differences were observed in Nugent scores and bacterial vaginosis between the two groups ( < .05). In functional analysis, 11 proteins and 13 enzymes were found to be significantly altered in the HPV + group.
CONCLUSION
Our study demonstrates that disruptions in the vaginal flora are associated with HPV infection. Reduced levels of , increased prevalence of , and abnormal enzyme profiles are closely linked to HPV infection.
Topics: Humans; Female; Papillomavirus Infections; Cross-Sectional Studies; Vagina; Adult; Microbiota; Lactobacillus; Gardnerella vaginalis; Vaginosis, Bacterial; Middle Aged; RNA, Ribosomal, 16S; Papillomaviridae; Young Adult; Cervix Uteri
PubMed: 38861397
DOI: 10.1080/01443615.2024.2361847 -
Nature Communications Jun 2024The differentiation of the stroma is a hallmark event during postnatal uterine development. However, the spatiotemporal changes that occur during this process and the...
The differentiation of the stroma is a hallmark event during postnatal uterine development. However, the spatiotemporal changes that occur during this process and the underlying regulatory mechanisms remain elusive. Here, we comprehensively delineated the dynamic development of the neonatal uterus at single-cell resolution and characterized two distinct stromal subpopulations, inner and outer stroma. Furthermore, single-cell RNA sequencing revealed that uterine ablation of Pr-set7, the sole methyltransferase catalyzing H4K20me1, led to a reduced proportion of the inner stroma due to massive cell death, thus impeding uterine development. By combining RNA sequencing and epigenetic profiling of H4K20me1, we demonstrated that PR-SET7-H4K20me1 either directly repressed the transcription of interferon stimulated genes or indirectly restricted the interferon response via silencing endogenous retroviruses. Declined H4K20me1 level caused viral mimicry responses and ZBP1-mediated apoptosis and necroptosis in stromal cells. Collectively, our study provides insight into the epigenetic machinery governing postnatal uterine stromal development mediated by PR-SET7.
Topics: Female; Animals; Uterus; Stromal Cells; Epigenesis, Genetic; Mice; Histone-Lysine N-Methyltransferase; Interferons; Endogenous Retroviruses; Apoptosis; Mice, Inbred C57BL; Cell Death; Necroptosis; RNA-Binding Proteins; Histones; Single-Cell Analysis; Mice, Knockout; Cell Differentiation
PubMed: 38858353
DOI: 10.1038/s41467-024-49342-6 -
BMJ Open Jun 2024Multiplathogen home-based self-sampling offers an opportunity to increase access to screening and treatment in endemic settings with high coinfection prevalence of...
Zipime-Weka-Schista study protocol: a longitudinal cohort study and economic evaluation of an integrated home-based approach for genital multipathogen screening in women, including female genital schistosomiasis, human papillomavirus, Trichomonas and HIV in Zambia.
INTRODUCTION
Multiplathogen home-based self-sampling offers an opportunity to increase access to screening and treatment in endemic settings with high coinfection prevalence of sexually transmitted (HIV, human papillomavirus (HPV)) and non-sexually transmitted pathogens ()). Chronic coinfections may lead to disability (female genital schistosomiasis) and death (cervical cancer). The Zipime-Weka-Schista (Do self-testing sister!) study aims to evaluate the validity, acceptability, uptake, impact and cost-effectiveness of multipathogen self-sampling for genital infections among women in Zambia.
METHODS AND ANALYSIS
This is a longitudinal cohort study aiming to enrol 2500 non-pregnant, sexually active and non-menstruating women aged 15-50 years from two districts in Zambia with 2-year follow-up. During home visits, community health workers offer HIV and self-testing and cervicovaginal self-swabs for (1) HPV by GeneXpert and, (2) DNA detection by conventional (PCR)and isothermal (recombinase polymerase assay) molecular methods. ova and circulating anodic antigen are detected in urine. At a clinic follow-up, midwives perform the same procedures and obtain hand-held colposcopic images. High-risk HPV positive women are referred for a two-quadrant cervical biopsy according to age and HIV status. A cost-effectiveness analysis is conducted in parallel.
ETHICS AND DISSEMINATION
The University of Zambia Biomedical Research Ethics Committee (UNZABREC) (reference: 1858-2021), the London School of Hygiene and Tropical Medicine (reference: 25258), Ministry of Health and local superintendents approved the study in September 2021.Written informed consent was obtained from all participants prior to enrolment. Identifiable data collected are stored securely and their confidentiality is protected in accordance with the Data Protection Act 1998.
Topics: Humans; Female; Zambia; Longitudinal Studies; Adult; Adolescent; Young Adult; Middle Aged; Cost-Benefit Analysis; Papillomavirus Infections; HIV Infections; Mass Screening; Coinfection; Self-Testing; Animals; Schistosomiasis haematobia; Trichomonas Vaginitis; Trichomonas vaginalis; Uterine Cervical Neoplasms; Human Papillomavirus Viruses
PubMed: 38858160
DOI: 10.1136/bmjopen-2023-080395 -
Trends in Molecular Medicine Jun 2024Countless efforts have been made to eradicate cervical cancer worldwide, including improving disease screening and human papillomavirus (HPV) vaccination programs.... (Review)
Review
Countless efforts have been made to eradicate cervical cancer worldwide, including improving disease screening and human papillomavirus (HPV) vaccination programs. Nevertheless, cervical cancer still claims the lives of more than 300 000 women every year. Persistent infections with high-risk HPV genotypes 16 and 18 are the main cause of cancer and may result in HPV integration into the host genome. The central dogma is that HPV integration is an important step in oncogenesis, but in fact, it impedes the virus from replicating and spreading. HPV causing cervical cancer can therefore be perceived as a failed evolutionary viral trait. Here we outline the occurrence and mechanisms of HPV integration and how this process results in oncogenic transformation.
PubMed: 38853085
DOI: 10.1016/j.molmed.2024.05.009 -
Cell Death Discovery Jun 2024Diverse mechanisms have been established to understand the chemoresistance of hepatocellular carcinoma (HCC), but the contribution of non-coding RNAs is not surveyed...
Diverse mechanisms have been established to understand the chemoresistance of hepatocellular carcinoma (HCC), but the contribution of non-coding RNAs is not surveyed well. Here, we aimed to explore the lncRNA-miRNA axis in Hepatitis C and B virus (HCV and HBV) infected HCC to investigate the molecular mechanism of chemoresistance and to identify a potential therapeutic target for HCC. The small RNA transcriptome analysis followed by qRT-PCR validation with the liver tissues of both HCV and HBV infected HCC patients revealed that miR-424-5p, miR-136-3p, miR-139-5p, miR-223-3p, and miR-375-3p were the most downregulated miRNAs in HCC compared to normal (log fold change ≤-1.5, P ≤ 0.05). In silico pathway analysis with the validated targets of each miRNA revealed that the signalling pathway regulating pluripotency of stem cells is commonly targeted by these five miRNAs. Subsequent validation by 3'UTR-luciferase assay and western blot analysis unveiled that these five miRNAs impeded either same or diverse genes, but all linked to BMP signalling pathway such as BMPR1A/BMPR1B by miR-139-5p, miR-136-3p, and miR-375-3p, and ACVR2A/ACVR2B by miR-424-5p and miR-223-3p. Furthermore, restoration of each miRNA in Huh7/SNU449 cells inhibited phosphorylation of downstream SMAD1/5 and ERK1/2, and attenuated Epithelial-mesenchymal transition, stemness, spheroid formation, chemoresistance, invasion and migration of cells. To investigate the mechanism of suppression of these miRNAs, "DIANA" tool was employed and lncRNA-KCNQ1OT1 was retrieved as interacting partner of all the five miRNAs. In vitro RNA pull-down assay revealed that lncRNA-KCNQ1OT1 physically interacted and sequestered these five miRNAs in the cytoplasm. Hence, KCNQ1OT1 was suppressed in Huh7/SNU449 cells using CRISPR technology and observed regression of oncogenic properties with enhanced chemosensitivity and reduced metastasis in cancer cells. Shrinkage of tumour size and volume in NOD-SCID mice injected with KCNQ1OT1-sgRNA cells further strengthened our observations. Thus, lncRNA-KCNQ1OT1 is the main regulator, which reduces the level of beneficiary miRNAs in the tumour milieu and modulates BMP signalling pathway to promote chemoresistance in HCC, suggesting lncRNA-KCNQ1OT1 might have robust potential to be a therapeutic target in HCC.
PubMed: 38851743
DOI: 10.1038/s41420-024-02016-0 -
Clinical Epigenetics Jun 2024The major challenge in routine endocervical curettage (ECC) among Human Papillomavirus (HPV) 16/18-positive patients is that only a small fraction benefit. Nevertheless,...
PAX1 methylation as a robust predictor: developing and validating a nomogram for assessing endocervical curettage (ECC) necessity in human papillomavirus16/18-positive women undergoing colposcopy.
OBJECTIVE
The major challenge in routine endocervical curettage (ECC) among Human Papillomavirus (HPV) 16/18-positive patients is that only a small fraction benefit. Nevertheless, current reported models often overestimate the validity and necessity of ECC, making it difficult to improve benefits for patients. This research hypothesized that assessing paired boxed gene 1 methylation levels (PAX1) and clinical characteristics could enhance the predictive accuracy of detecting additional high-grade squamous intraepithelial lesions or worse (HSIL +) through ECC that were not identified by colposcopy-directed biopsy (CDB).
METHODS
Data from 134 women with HPV16/18 positivity undergoing CDB and ECC between April 2018 and April 2022 were collected and analyzed. Quantitative methylation-specific polymerase chain reaction (qMSP) was utilized to measure PAX1, expressed as ΔCp. Univariate and multivariate regression analyses were conducted to screen variables and select predictive factors. A nomogram was constructed using multivariate logistic regression to predict additional HSIL + detected by ECC. The discrimination, calibration, and clinical utility of the nomogram were evaluated using receiver operating characteristic curves (ROC) and the calibration plot.
RESULTS
Age (odds ratio [OR], 5.654; 95% confidence interval [CI], 1.131-37.700), cytology (OR, 24.978; 95% CI, 3.085-540.236), and PAX1 methylation levels by grade (PAX1 grade) (OR, 7.801; 95% CI, 1.548-44.828) were independent predictive factors for additional detection of HSIL + by ECC. In HPV16/18-positive women, the likelihood of additional detection of HSIL + through ECC increased with the severity of cytological abnormalities, peaking at 43.8% for high-grade cytological lesions. Moreover, when cytological findings indicated low-grade lesions, PAX1 methylation levels were positively correlated with the additional detection of HSIL + by ECC (P value < 0.001). A nomogram prediction model was developed (area under curve (AUC) = 0.946; 95% CI, 0.901-0.991), demonstrating high sensitivity (90.9%) and specificity (90.5%) at the optimal cutoff point of 107. Calibration analysis confirmed the model's strong agreement between predicted and observed probabilities.
CONCLUSION
The clinical nomogram presented promising predictive performance for the additional detection of HSIL + through ECC among women with HPV16/18 infection. PAX1 methylation level could serve as a valuable tool in guiding individualized clinical decisions regarding ECC for patients with HPV 16/18 infection, particularly in cases of low-grade cytological findings.
Topics: Humans; Female; Paired Box Transcription Factors; Human papillomavirus 16; Nomograms; Adult; DNA Methylation; Middle Aged; Human papillomavirus 18; Papillomavirus Infections; Colposcopy; Uterine Cervical Neoplasms; Curettage; ROC Curve; Uterine Cervical Dysplasia; Cervix Uteri
PubMed: 38849868
DOI: 10.1186/s13148-024-01691-1 -
Virus Research Aug 2024The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other...
The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other diseases in immunosuppressed individuals, including granule cell neuronopathy, JCV-associated nephropathy, encephalitis, and meningitis in rare cases. JCV classification is still unclear, where the ICTV (International Committee on Taxonomy of Viruses) has grouped all the strains into human polyomavirus 2, with no classification on clade and subclade levels. Therefore, JCV strains were previously classified using different genomic regions, e.g., full-length, VP1, and the V-T intergenic region etc., and the strains were grouped into several types related to various geographic locations and human ethnicities. However, neither of these classifications and nomenclature contemplates all the groups described so far. Herein, we evaluated all the available full-length coding genomes, VP1, and large T antigen nucleotide sequences of JCV reported during 1993-2023 and classified them into four major phylogenetic clades, i.e., GI-GIV, where GI is further grouped into two types GI.1 and GI.2 with five sub-clades each (GI.1/GI.2 a-e), GII into three (GII a-c), GIII as a separate clade, and GIV into seven sub-clades (GIV a-g). Similarly, the phylogeographic network analysis indicated four major clusters corresponding to GI-GIV clades, each with multiple subclusters and mutational sub-branches corresponding to the subclades. GI and GIV clusters are connected via GI.1-e reported from Europe and America, GII, GIII and GIV clusters are connected by GII-b and GII-c strains reported from Africa, while GIV cluster strains are connected to the Russia-Italy JCV haplotype. Furthermore, we identified JCV-variant-GS/B-Germany-1997 (GenBank ID: AF004350.1) as an inter-genotype recombinant having major and minor parents in the GI.1-e and GII-a clades, respectively. Additionally, the amino acid variability analysis revealed high entropy across all proteins. The large T antigen exhibited the highest variability, while the small t antigen showed the lowest variability. Our phylogenetic and phylogeographic analyses provide a new approach to genotyping and sub-genotyping and present a comprehensive classification system of JCV strains based on their genetic characteristics and geographic distribution, while the genetic recombination and amino acid variability can help identify pathogenicity and develop effective preventive and control measures against JCV infections.
Topics: JC Virus; Phylogeography; Humans; Phylogeny; Genome, Viral; Leukoencephalopathy, Progressive Multifocal; Polyomavirus Infections; Genetic Variation; Cluster Analysis
PubMed: 38848817
DOI: 10.1016/j.virusres.2024.199414 -
PloS One 2024Cervical cancer, a malignancy caused by infection with oncogenic human papillomavirus, disproportionally affects women from low resource settings. Persistence of human...
INTRODUCTION
Cervical cancer, a malignancy caused by infection with oncogenic human papillomavirus, disproportionally affects women from low resource settings. Persistence of human papillomavirus infection may mediate an association between tobacco use and cervical cancer. In limited resource settings, women from indigenous communities are often marginalized and do not benefit from evidence-based interventions to prevent tobacco use or cervical cancer due to the limited reach of mainstream healthcare services to these communities. This study determined the association between smoking and high-risk human papillomavirus infection among women from indigenous communities in western Botswana.
METHODS
A cross-sectional study of women in indigenous communities was conducted between June and October 2022. Demographic, clinical and self-reported smoking data were collected. Cervical cytology and HPV DNA testing for high-risk human papillomavirus genotypes were performed. Multilevel multivariable logistic regression models were fit to evaluate the association between smoking and high-risk human papillomavirus infection while adjusting for potential confounders.
RESULTS
A total of 171 participants with a median (interquartile range) age of 40 (31-50) years from three settlements and two villages were recruited for the study. Of these, 17% were current smokers, 32.8% were living with HIV and high-risk human papillomavirus DNA was detected in 32.8% of the cervical specimens. Women who were current smokers, were nearly twice as likely to have cervical high-risk human papillomavirus infection compared to non-smokers (Adjusted Odds Ratio (95% CI); 1.74(1.09, 2.79)) after controlling for confounders.
CONCLUSION
These data underscore the need for effective tobacco control to help mitigate cervical cancer risk in this setting. These findings can help inform decisions about targeted cervical cancer prevention and tobacco cessation interventions for women from indigenous communities.
Topics: Humans; Female; Papillomavirus Infections; Botswana; Adult; Middle Aged; Cross-Sectional Studies; Uterine Cervical Neoplasms; Smoking; Indigenous Peoples; Papillomaviridae; Risk Factors
PubMed: 38848414
DOI: 10.1371/journal.pone.0302153