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Viruses May 2024DNA viruses that produce persistent infections have been proposed as potential causes for the extinction of Neanderthals, and, therefore, the identification of viral...
DNA viruses that produce persistent infections have been proposed as potential causes for the extinction of Neanderthals, and, therefore, the identification of viral genome remnants in Neanderthal sequence reads is an initial step to address this hypothesis. Here, as proof of concept, we searched for viral remnants in sequence reads of Neanderthal genome data by mapping to adenovirus, herpesvirus and papillomavirus, which are double-stranded DNA viruses that may establish lifelong latency and can produce persistent infections. The reconstructed ancient viral genomes of adenovirus, herpesvirus and papillomavirus revealed conserved segments, with nucleotide identity to extant viral genomes and variable regions in coding regions with substantial divergence to extant close relatives. Sequence reads mapped to extant viral genomes showed deamination patterns of ancient DNA, and these ancient viral genomes showed divergence consistent with the age of these samples (≈50,000 years) and viral evolutionary rates (10 to 10 substitutions/site/year). Analysis of random effects showed that the Neanderthal mapping to genomes of extant persistent viruses is above what is expected by random similarities of short reads. Also, negative control with a nonpersistent DNA virus does not yield statistically significant assemblies. This work demonstrates the feasibility of identifying viral genome remnants in archaeological samples with signal-to-noise assessment.
Topics: Animals; Neanderthals; Genome, Viral; DNA, Ancient; Evolution, Molecular; DNA, Viral; Sequence Analysis, DNA; Humans; Phylogeny; DNA Viruses; Fossils
PubMed: 38932149
DOI: 10.3390/v16060856 -
Microorganisms Jun 2024We present the validity of using an ultrasensitive enzyme-linked immunosorbent assay (ELISA) for quantifying high-risk human papillomavirus (HPV) 16 E7 oncoproteins in...
We present the validity of using an ultrasensitive enzyme-linked immunosorbent assay (ELISA) for quantifying high-risk human papillomavirus (HPV) 16 E7 oncoproteins in urine specimens as a noninvasive method of analyzing the oncogenic activity of HPV. Some reports claim that the oncogenic activity of HPV is a more relevant clinical indicator than the presence of HPV DNA for estimating malignant potential. In the present study, urine containing HPV16 and related types were selected by uniplex E6/E7 polymerase chain reaction and classified according to the pathologic diagnosis of cervical intraepithelial neoplasia (CIN) in cervical biopsy specimens. Our ultrasensitive ELISA was able to detect attomole levels of HPV16 E7 oncoproteins, and it detected HPV16-positive SiHa cells at >500 cells/mL without detecting HPV18-positive cells. Our ELISA results showed E7 oncoproteins in 80% (4/5) of urine specimens from women with HPV16-positive CIN1, 71% (5/7) of urine specimens from CIN2 patients, and 38% (3/8) of urine specimens from CIN3 patients. Some urine specimens with undetectable E7 oncoproteins were thought to be negative for live HPV 16-positive cells or in an inactivated state of infection. These results provide the basis for assessing oncogenic activity by quantifying E7 oncoproteins in patient urine.
PubMed: 38930587
DOI: 10.3390/microorganisms12061205 -
Microorganisms May 2024Some infectious agents have the potential to cause specific modifications in the cellular microenvironment that could be propitious to the carcinogenesis process.... (Review)
Review
Some infectious agents have the potential to cause specific modifications in the cellular microenvironment that could be propitious to the carcinogenesis process. Currently, there are specific viruses and bacteria, such as human papillomavirus (HPV) and , that are well established as risk factors for neoplasia. (CT) infections are one of the most common bacterial sexually transmitted infections worldwide, and recent European data confirmed a continuous rise across Europe. The infection is often asymptomatic in both sexes, requiring a screening program for early detection. Notwithstanding, not all countries in Europe have it. can cause chronic and persistent infections, resulting in inflammation, and there are plausible biological mechanisms that link the genital infection with tumorigenesis. Herein, we aimed to understand the epidemiological and biological plausibility of CT genital infections causing endometrial, ovarian, and cervical tumors. Also, we covered some of the best suitable in vitro techniques that could be used to study this potential association. In addition, we defend the point of view of a personalized medicine strategy to treat those patients through the discovery of some biomarkers that could allow it. This review supports the need for the development of further fundamental studies in this area, in order to investigate and establish the role of chlamydial genital infections in oncogenesis.
PubMed: 38930508
DOI: 10.3390/microorganisms12061126 -
Medicina (Kaunas, Lithuania) Jun 2024: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia...
: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia is one of the highest among European countries, and this cancer is the second-leading cause of death in Serbian women aged from 15 to 44. : This retrospective study was conducted at the Institute of Public Health of Vojvodina. A total of 10,062 cervical specimens from Serbian women were collected and HPV tested in ten years. The study patients were divided into five age groups. HPV genotype testing was performed using a commercial kit to detect 14 high-risk (HR) HPV genotypes. Additionally, cervix cytology data have been available for patients tested in 2022 and 2023. : An overall positive rate was found in 43.3% of patients (4356/10,062). A single HPV infection (62.1%) was the main infection pattern. The most frequent HR HPV genotypes were HPV 16, 31, 52, 56, 39, and 51, comprising 62.3% of the detected genotypes, including multiple infections. A significant difference was noted in the HPV prevalence across the different age groups, with a bimodal distribution of HPV infection. The highest prevalence was recorded in the age group ≤ 30 and those after 61 years. Women diagnosed with high-grade squamous intraepithelial lesions (HSIL) were significantly older compared to others. HR HPV is the most prevalent in patients with HSIL cytological findings (76.5%). The most common type, according to age-specific distribution and cytological findings, was HR HPV 16. : This study provides comprehensive data on HR HPV distribution among Serbian women, which can serve as a basis for subsequent monitoring of genotypic distribution. It is particularly significant considering they are missing in the updated ICO/IARC Report for Serbia, and the cervical cancer mortality rate in Serbia is one of the highest among European countries.
Topics: Humans; Female; Serbia; Papillomavirus Infections; Adult; Retrospective Studies; Genotype; Prevalence; Middle Aged; Adolescent; Papillomaviridae; Uterine Cervical Neoplasms; Young Adult; Aged
PubMed: 38929539
DOI: 10.3390/medicina60060922 -
Medicina (Kaunas, Lithuania) May 2024: Cervical cancer is the fourth most frequent type of neoplasia in women. It is most commonly caused by the persistent infection with high-risk strands of human...
: Cervical cancer is the fourth most frequent type of neoplasia in women. It is most commonly caused by the persistent infection with high-risk strands of human papillomavirus (hrHPV). Its incidence increases rapidly from age 25 when routine HPV screening starts and then decreases at the age of 45. This reflects both the diagnosis of prevalent cases at first-time screening and the likely peak of HPV exposure in early adulthood. For early stages, the treatment offers the possibility of fertility preservation.. However, in more advanced stages, the treatment is restricted to concomitant chemo-radiotherapy, combined, in very selected cases with surgical intervention. After the neoadjuvant treatment, an imagistic re-evaluation of the patients is carried out to analyze if the stage of the disease remained the same or suffered a downstaging. Lymph node downstaging following neoadjuvant treatment is regarded as an indubitable prognostic factor for predicting disease recurrence and survival in patients with advanced cervical cancer. This study aims to ascertain the important survival role of radiotherapy in the downstaging of the disease and of lymphadenectomy in the control of lymph node invasion for patients with advanced-stage cervical cancer. : We describe the outcome of patients with cervical cancer in stage IIIC1 FIGO treated at Bucharest Oncological Institute. All patients received radiotherapy and two-thirds received concomitant chemotherapy. A surgical intervention consisting of type C radical hysterectomy with radical pelvic lymphadenectomy was performed six to eight weeks after the end of the neoadjuvant treatment. : The McNemar test demonstrated the regression of lymphadenopathies after neoadjuvant treatment-: <0.001. However, the persistence of adenopathies was not related to the dose of irradiation (: 0.61), the number of sessions of radiotherapy (: 0.80), or the chemotherapy (: 0.44). Also, there were no significant differences between the adenopathies reported by imagistic methods and those identified during surgical intervention-: 0.62. The overall survival evaluated using Kaplan-Meier curves is dependent on the post-radiotherapy FIGO stage-: 0.002 and on the lymph node status evaluated during surgical intervention-: 0.04. The risk factors associated with an increased risk of death were represented by a low preoperative hemoglobin level (: 0.003) and by the advanced FIGO stage determined during surgical intervention (-value: 0.006 for stage IIIA and 0.01 for stage IIIC1). In the multivariate Cox model, the independent predictor of survival was the preoperative hemoglobin level (: 0.004, HR 0.535, CI: 0.347 to 0.823). Out of a total of 33 patients with neoadjuvant treatment, 22 survived until the end of the study, all 33 responded to the treatment in varying degrees, but in 3 of them, tumor cells were found in the lymph nodes during the intraoperative histopathological examination. : For advanced cervical cancer patients, radical surgery after neoadjuvant treatment may be associated with a better survival rate. Further research is needed to identify all the causes that lead to the persistence of adenopathies in certain patients, to decrease the FIGO stage after surgical intervention, and, therefore, to lower the risk of death. Also, it is mandatory to correctly evaluate and treat the anemia, as it seems to be an independent predictor factor for mortality.
Topics: Humans; Female; Uterine Cervical Neoplasms; Neoadjuvant Therapy; Adult; Middle Aged; Neoplasm Staging; Lymph Node Excision; Lymph Nodes; Hysterectomy; Lymphatic Metastasis; Aged
PubMed: 38929488
DOI: 10.3390/medicina60060871 -
Cancers Jun 2024Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated...
Synergistic Effect of Human Papillomavirus and Environmental Factors on Skin Squamous Cell Carcinoma, Basal Cell Carcinoma, and Melanoma: Insights from a Taiwanese Cohort.
Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated with HPV infection in Taiwan region, using data from the National Health Insurance Research Database between 2007 and 2015. Our analysis revealed a significant increase in skin cancer risk among those with HPV, particularly for squamous cell carcinoma (SCC), the subtype with the highest observed adjusted hazard ratio (aHR) = 5.97, 95% CI: 4.96-7.19). The overall aHR for HPV-related skin cancer was 5.22 (95% CI: 4.70-5.80), indicating a notably higher risk in the HPV-positive group. The risk of skin cancer was further stratified by type, with basal cell carcinoma (aHR = 4.88, 95% CI: 4.14-5.74), and melanoma (aHR = 4.36, 95% CI: 2.76-6.89) also showing significant associations with HPV. The study also highlighted regional variations, with increased risks in southern Taiwan and the Kaohsiung-Pingtung area. Key findings emphasize the importance of sun protection, particularly in regions of high UV exposure and among individuals in high-risk occupations. This research contributes to a better understanding of the complex interactions between HPV and skin cancer risk, reinforcing the importance of preventive strategies in public health.
PubMed: 38927988
DOI: 10.3390/cancers16122284 -
Cancers Jun 2024The aim of the study was to evaluate the impact of urine-sample HPV (human papillomavirus) testing on the effectiveness of screening for cervical cancer. (Review)
Review
BACKGROUND
The aim of the study was to evaluate the impact of urine-sample HPV (human papillomavirus) testing on the effectiveness of screening for cervical cancer.
METHODS
The analysis was based on the results of a systematic review. Secondary studies were searched in the following medical databases: Medline, Embase, and the Cochrane Library. The results of the statistical tests presented in the article originate from research conducted by the authors of the included articles.
RESULTS
From a total of 1869 citations, 5 studies were included in this review. Sensitivity and specificity for the detection of any HPV from first-void urine samples were 87% [95% CI: (0.74; 0.94)] and 89% [95% CI: (0.81; 0.93)], respectively. Moreover, participants in the analyzed studies had indicated that they felt comfortable with urine testing.
CONCLUSIONS
The development of methods to detect HPV infection in first-void urine samples and the application of this sampling method in widely available screening tests could significantly increase patients' willingness to participate in testing.
PubMed: 38927949
DOI: 10.3390/cancers16122244 -
Cancers Jun 2024HPV 16 integration is crucial for the onset and progression of premalignant lesions to invasive squamous cell carcinoma (ISCC) because it promotes the amplification of...
HPV 16 integration is crucial for the onset and progression of premalignant lesions to invasive squamous cell carcinoma (ISCC) because it promotes the amplification of proto-oncogenes and the silencing of tumor suppressor genes; some of these are proteins with PDZ domains involved in homeostasis and cell polarity. Through a bioinformatics approach based on interaction networks, a group of proteins associated with HPV 16 infection, PDZ domains, and direct physical interaction with E6 and related to different hallmarks of cancer were identified. MAGI-1 was selected to evaluate the expression profile and subcellular localization changes in premalignant lesions and ISCC with HPV 16 in an integrated state in cervical cytology; the profile expression of MAGI-1 diminished according to lesion grade. Surprisingly, in cell lines CaSki and SiHa, the protein localization was cytoplasmic and nuclear. In contrast, in histological samples, a change in subcellular localization from the cytoplasm in low-grade squamous intraepithelial lesions (LSIL) to the nucleus in the high-grade squamous intraepithelial lesion (HSIL) was observed; in in situ carcinomas and ISCC, MAGI-1 expression was absent. In conclusion, MAGI-1 expression could be a potential biomarker for distinguishing those cells with normal morphology but with HPV 16 integrated from those showing morphology-related uterine cervical lesions associated with tumor progression.
PubMed: 38927930
DOI: 10.3390/cancers16122225 -
Genes May 2024Glycogen synthase kinase-3β (GSK3β) not only plays a crucial role in regulating sperm maturation but also is pivotal in orchestrating the acrosome reaction. Here, we...
Glycogen synthase kinase-3β (GSK3β) not only plays a crucial role in regulating sperm maturation but also is pivotal in orchestrating the acrosome reaction. Here, we integrated single-molecule long-read and short-read sequencing to comprehensively examine expression patterns in adult Diannan small-ear pig (DSE) testes. We identified the most important transcript ENSSSCT00000039364 of , obtaining its full-length coding sequence (CDS) spanning 1263 bp. Gene structure analysis located on pig chromosome 13 with 12 exons. Protein structure analysis reflected that consisted of 420 amino acids containing PKc-like conserved domains. Phylogenetic analysis underscored the evolutionary conservation and homology of across different mammalian species. The evaluation of the protein interaction network, KEGG, and GO pathways implied that GSK3β interacted with 50 proteins, predominantly involved in the Wnt signaling pathway, papillomavirus infection, hippo signaling pathway, hepatocellular carcinoma, gastric cancer, colorectal cancer, breast cancer, endometrial cancer, basal cell carcinoma, and Alzheimer's disease. Functional annotation identified that was involved in thirteen GOs, including six molecular functions and seven biological processes. ceRNA network analysis suggested that DSE was regulated by 11 miRNA targets. Furthermore, qPCR expression analysis across 15 tissues highlighted that was highly expressed in the testis. Subcellular localization analysis indicated that the majority of the GSK3β protein was located in the cytoplasm of ST (swine testis) cells, with a small amount detected in the nucleus. Overall, our findings shed new light on 's role in DSE reproduction, providing a foundation for further functional studies of function.
Topics: Animals; Glycogen Synthase Kinase 3 beta; Male; Swine; Spermatogenesis; Testis; Phylogeny; Gene Expression Regulation
PubMed: 38927591
DOI: 10.3390/genes15060655 -
NPJ Vaccines Jun 2024Persistent infection with high-risk human papillomavirus (HPV) is widely recognized as the primary cause of cervical and other malignant cancers. There are six licensed...
Persistent infection with high-risk human papillomavirus (HPV) is widely recognized as the primary cause of cervical and other malignant cancers. There are six licensed prophylactic vaccines available against HPV, but none of them shows any significant therapeutic effect on pre-existing infections or lesions. Thus, a prophylactic vaccine also endowed with therapeutic activity would afford protection regardless of the vaccine recipients HPV-infection status. Here, we describe the refinement and further potentiation of a dual-purpose HPV nanoparticle vaccine (hereafter referred to as cPANHPVAX) relying on eight different HPV L2 peptide epitopes and on the E7 oncoantigens from HPV16 and 18. cPANHPVAX not only induces anti-HPV16 E7 cytotoxic T-cell responses in C57BL/6 mice, but also anti-HPV18 E7 T-cell responses in transgenic mice with the A2.DR1 haplotype. These cytotoxic responses add up to a potent, broad-coverage humoral (HPV-neutralizing) response. cPANHPVAX safety was further improved by deletion of the pRb-binding domains of E7. Our dual-purpose vaccine holds great potential for clinical translation as an immune-treatment capable of targeting active infections as well as established HPV-related malignancies, thus benefiting both uninfected and infected individuals.
PubMed: 38926425
DOI: 10.1038/s41541-024-00914-z