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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 -
Scientific Data Jun 2024The Cervical Screening Cohort enrols women screened for human papillomavirus (HPV) and cervical abnormalities within the capital region of Sweden from the organised...
The Cervical Screening Cohort enrols women screened for human papillomavirus (HPV) and cervical abnormalities within the capital region of Sweden from the organised screening program and the non-organised testing of cervical samples. The cohort started in 2011 and has enrolled more than 670,000 women, contributing with more than 1.2 million biobanked samples. The cohort is systematically updated with individual-level data from the Swedish National Cervical Screening Registry (NKCx). Key variables include birthdate, sampling date, cytological, histopathological and HPV analysis results, and invitation history. Each sampling and subsequent clinical follow-up is sequentially registered, allowing for longitudinal analyses of screening results and associated results of the clinical workup. The cohort is ideal for longitudinal, long-term follow-up studies due to its validated documentation and registry-derived information. From the data, it is possible to penetrate important human health mechanisms. The data are available as open-data and GDPR-compliant. Samples are available after getting the required permissions. Results will help researchers understand factors that increase cancer risk and other diseases.
Topics: Humans; Sweden; Female; Uterine Cervical Neoplasms; Papillomavirus Infections; Early Detection of Cancer; Cohort Studies; Registries; Mass Screening; Adult; Cervix Uteri; Papillomaviridae; Middle Aged
PubMed: 38926412
DOI: 10.1038/s41597-024-03519-2 -
Sexually Transmitted Infections Jun 2024Specific to sexual health, individuals in need of information may be adolescents who have limited ability to formally access healthcare. These digital natives may turn...
OBJECTIVES
Specific to sexual health, individuals in need of information may be adolescents who have limited ability to formally access healthcare. These digital natives may turn to ChatGPT to address their concerns on sexually transmitted infections (STI). We sought to evaluate the veracity of ChatGPT's responses to commonly asked questions on STIs.
METHODS
We instructed ChatGPT (GPT 3.5) to answer STI questions from three domains, namely, (1) general risk factors for STIs, (2) access to care and diagnosis of STIs and (3) management of STIs and postexposure prophylaxis. The responses were recorded and checked against the US Centers for Disease Control and Prevention STI Treatment Guidelines 2021.
RESULTS
Overall, the responses were concise and accurate. In terms of prevention, ChatGPT could also recommend measures like safe sex practices and human papillomavirus vaccination. However, it failed to recommend HIV pre-exposure prophylaxis. When an individual expressed a symptom that could potentially represent STI (eg, dyspareunia) ChatGPT appropriately provided reassurance that other possibilities exist, but advocated for testing. In terms of treatment, ChatGPT consistently communicated the importance of partner testing and follow-up testing, but at times, failed to highlight the importance of testing for other STIs. Overall, the advice given was not tailored to the specific individual's circumstances.
CONCLUSIONS
ChatGPT can provide helpful information regarding STIs, but the advice lacks specificity and requires a human physician to fine-tune. Its ubiquity may make it a useful adjunct to sexual health clinics, to improve knowledge and access to care.
PubMed: 38925936
DOI: 10.1136/sextrans-2024-056217 -
Anticancer Research Jul 2024Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is clinically and immunologically distinct from HPV-negative HNSCC. Herein, we...
BACKGROUND/AIM
Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is clinically and immunologically distinct from HPV-negative HNSCC. Herein, we investigated the presence of tumor antigens HPV E6/E7 and wild-type p53-specific T-cell responses, and the impact of immune checkpoint blockade in patients with HPV-positive HNSCC.
MATERIALS AND METHODS
Peripheral blood mononuclear cells (PBMCs) from patients with HPV-positive HNSCC were stimulated with HPV E6/E7 or wild-type p53-derived peptide mixture and evaluated using the interferon-γ enzyme-linked immunosorbent spot assay. Flow cytometry was performed to analyze the proportion of T-cell subsets and T cells expressing immune checkpoint molecules.
RESULTS
HPV E6/E7-specific T cells were detected in 22 (95.7%) of 23 patients, whereas wild-type p53-specific T cells were detected in 3 (15.0%) of 20 patients. Seven (43.8%) of 16 patients exhibited wild-type p53-specific T-cell responses, as determined using whole proteins instead of peptides. Immune checkpoint blockade enhanced wild-type p53-specific T-cell responses in 9 (45.0%) of 20 patients. Flow cytometric analysis of PBMCs revealed that responders exhibiting enhanced wild-type p53-specific T-cell responses following immune checkpoint blockade had a significantly higher proportion of Ki-67+CD4+ T cells, Ki-67+CD8+ T cells, regulatory T cells, PD-1+CD4+ T cells, and TIM-3+CD4+ T cells than non-responders.
CONCLUSION
Our findings indicate that tumor antigen-specific T cells are present in the peripheral blood of patients with HPV-positive HNSCC. Blockade of checkpoint pathways can enhance T-cell responses in certain patients, probably via activated T cells, Tregs, and/or exhausted CD4+ T cells.
Topics: Humans; Immune Checkpoint Inhibitors; Squamous Cell Carcinoma of Head and Neck; Male; Female; Middle Aged; Aged; Head and Neck Neoplasms; Papillomavirus Infections; Antigens, Neoplasm; Oncogene Proteins, Viral; Tumor Suppressor Protein p53; Adult; Leukocytes, Mononuclear; Papillomaviridae; T-Lymphocytes; Human Papillomavirus Viruses
PubMed: 38925841
DOI: 10.21873/anticanres.17104 -
The Urologic Clinics of North America Aug 2024Penile cancer is a rare malignancy with a poor prognosis. Studies with single-agent immune checkpoint inhibitors (ICIs) have demonstrated efficacy, but response rates... (Review)
Review
Penile cancer is a rare malignancy with a poor prognosis. Studies with single-agent immune checkpoint inhibitors (ICIs) have demonstrated efficacy, but response rates are low. Studies combining ICIs with both chemotherapy and targeted therapy are ongoing. Up to 50% of penile cancer cases are associated with human papillomavirus (HPV). HPV-targeting therapies, such as HPV-targeting vaccines and T-cell receptor therapies, are an area of active investigation. Penile cancer cells also express cell surface antigens that may be targeted by the emerging class of antibody-drug conjugates.
Topics: Humans; Penile Neoplasms; Male; Immune Checkpoint Inhibitors; Papillomavirus Infections; Immunotherapy; Neoplasm Metastasis; Molecular Targeted Therapy
PubMed: 38925739
DOI: 10.1016/j.ucl.2024.03.005 -
The Urologic Clinics of North America Aug 2024This article reviews penile squamous cell carcinoma (PSCC), a rare genitourinary cancer that has been increasing in prevalence. It discusses emerging therapies, focusing... (Review)
Review
This article reviews penile squamous cell carcinoma (PSCC), a rare genitourinary cancer that has been increasing in prevalence. It discusses emerging therapies, focusing on immunotherapy, vaccine therapy, and cell-based treatments, especially in the context of human papillomavirus-related PSCC. Factors influencing these therapies are discussed. These include the immune microenvironment, programmed cell death ligand-1 expression, and tumor immune cell infiltration. This article also highlights immune checkpoint inhibitors and related clinical trials. This review supports the use of personalized medicine in treating PSCC. It stresses the need for collaborative studies and data sharing to create specific treatment plans and achieve better outcomes.
Topics: Humans; Penile Neoplasms; Male; Immunotherapy; Carcinoma, Squamous Cell; Immune Checkpoint Inhibitors; Tumor Microenvironment
PubMed: 38925738
DOI: 10.1016/j.ucl.2024.03.014 -
The Urologic Clinics of North America Aug 2024The landscape of squamous cell carcinoma of the penis (SCC-P) has undergone a significant transformation since the new World Health Organization classification of... (Review)
Review
The landscape of squamous cell carcinoma of the penis (SCC-P) has undergone a significant transformation since the new World Health Organization classification of genitourinary cancers and recent European Association of Urology/American Association of Clinical Oncology guidelines. These changes emphasize the necessity to categorize SCC-P into 2 groups based on its association with human papillomavirus (HPV) infection. This shift has major implications, considering that prior knowledge was derived from a mix of both groups. Given the distinct prognosis, treatment options, and staging systems observed for HPV-associated tumors in other body areas, the question now arises: will similar patterns emerge for SCC-P?
Topics: Humans; Penile Neoplasms; Male; Carcinoma, Squamous Cell; Papillomavirus Infections; Neoplasm Staging; Prognosis
PubMed: 38925734
DOI: 10.1016/j.ucl.2024.03.003