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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 -
The American Journal of Medicine Jun 2024Human papillomavirus (HPV) is the most common sexually transmitted infection in the US and worldwide, with more than 42 million Americans infected with types of HPV that... (Review)
Review
Human papillomavirus (HPV) is the most common sexually transmitted infection in the US and worldwide, with more than 42 million Americans infected with types of HPV that are known to cause disease. While the link between HPV and the development of a variety of cancers has been strongly established, recent literature has demonstrated a potential association between HPV and increased risk of cardiovascular disease. Nevertheless, despite plausible mechanisms for the development of cardiovascular disease with HPV infection, a causative relationship has yet to be firmly established, in part due to potential confounding risk factors between the two. In this 2-part series, we discuss the emerging relationship between HPV and cardiovascular disease. In part 1, we focus on the pathophysiology of HPV infection and potential mechanisms for the development of cardiovascular disease.
PubMed: 38925496
DOI: 10.1016/j.amjmed.2024.06.018 -
Microbial Pathogenesis Jun 2024With the knowledge of female reproductive tract microbiota gradually increasing, the connection between vaginal microbiota (VMB) and its related diseases is increasingly... (Review)
Review
With the knowledge of female reproductive tract microbiota gradually increasing, the connection between vaginal microbiota (VMB) and its related diseases is increasingly highlighted. Manifestation of VMB keeps changing with various dominated bacteria, which can affect the immune response of mucosal barrier and the entrance of pathogens. Human papillomavirus (HPV), as an oncogenic virus, is closely related to viral-associated cancer, such as cervical cancer. According to HPV infection status, VMB can transform into different types, and result in accelerating or restraining the progression of diseases,which have exposed the inner link between VMB and HPV. Therefore, probiotics therapy promises to be a new complementary therapy to rebuild a healthy VMB for patients, but there's still a long way to go before it's ready for the clinic. This review focuses on composition, immune response, and application of VMB in HPV and its associated diseases and aims to provide the new ideas and directions for the research on VMB.
PubMed: 38925345
DOI: 10.1016/j.micpath.2024.106761 -
Modern Pathology : An Official Journal... Jun 2024Vulvar lichen sclerosus (LS) is an inflammatory dermatosis which can progress to human papillomavirus (HPV-)independent vulvar intraepithelial neoplasia (HPVi VIN) and...
Vulvar lichen sclerosus (LS) is an inflammatory dermatosis which can progress to human papillomavirus (HPV-)independent vulvar intraepithelial neoplasia (HPVi VIN) and vulvar squamous cell carcinoma (VSCC). Although LS has a much lower cancer risk compared to HPVi VIN (5% versus 50%, respectively), its incidence is significantly higher. Therefore, there is a clinical need to identify LS patients with an increased cancer risk. Our objective was to study the value of DNA methylation and p53 immunohistochemistry (IHC) as prognostic biomarkers for progression to cancer in patients with LS. Vulvar tissues from 236 patients were selected, including 75 LS and 68 HPVi VIN, both with and without cancer development, 32 VSCC and 61 healthy vulvar controls. Samples were subjected to p53 IHC and DNA methylation analysis of a three-gene marker panel containing ZNF582, SST and miR124-2. Methylation levels and p53 IHC status (mutant or wild-type) were assessed and compared among all disease categories. Odds ratios (ORs) were determined to identify whether the biomarkers were associated with progression to cancer in patients with LS. Highest methylation levels were found in HPVi VIN and VSCC, followed by LS and healthy vulvar controls. The largest heterogeneity in methylation levels was observed in LS cases. In fact, the three-marker panel tested positive in 70% of LS which progressed to VSCC versus only 17% of LS in patients without cancer development (p=0.002). Also, mutant p53 IHC was observed more frequently in LS with progression to VSCC as compared to non-progressive LS cases (42% versus 3%, respectively, p=0.001). Multivariable analysis identified a mutant p53 status as the only independent risk factor for cancer development in LS (OR 34.0, 95% CI: 1.4 - 807.4). In conclusion, DNA methylation testing and p53 IHC show strong potential as prognostic biomarkers for the identification of LS patients at high risk of progression to cancer.
PubMed: 38925253
DOI: 10.1016/j.modpat.2024.100553