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Asian Pacific Journal of Cancer... Jun 2024
Review
Topics: Humans; India; Papillomavirus Vaccines; Health Knowledge, Attitudes, Practice; Papillomavirus Infections; Vaccination; Papillomaviridae; Uterine Cervical Neoplasms; Human Papillomavirus Viruses
PubMed: 38918643
DOI: 10.31557/APJCP.2024.25.6.1857 -
Scientific Reports Jun 2024High-risk human papillomavirus (HR-HPV) is the primary carcinogen in uterine cervical carcinoma. While genotype-specific carcinogenic risks have been extensively studied...
High-risk human papillomavirus (HR-HPV) is the primary carcinogen in uterine cervical carcinoma. While genotype-specific carcinogenic risks have been extensively studied in Western populations, data from Korean are sparse. This study evaluates the malignant potential of the three most prevalent HR-HPVs in Korea: HPV16, HPV52, and HPV58. We analyzed 230 patients who underwent cervical conization and had been tested for HPV within a year prior to the procedure, excluding those with multiple infections. This analysis was confined to patients with single HPV infections and assessed outcomes of CIN3+, which includes carcinoma in situ (CIN3) and invasive carcinoma. The incidence of invasive cervical cancer was 6.7% for HPV16, 1.7% for HPV52, and 2.0% for HPV58; however, these differences were not statistically significant (p = 0.187). The rate of CIN3+ for HPV16, HPV52, and HPV58 were 70.6%, 51.7%, and 58.8%, respectively. Despite the small sample size, which may limit the robustness of statistical analysis, the data suggest a higher observed risk with HPV16. These findings highlight the need for vigilant clinical management tailored to specific HPV genotypes and support the implementation of a nine-valent vaccine in Korea. Physicians should be aware of these genotype-specific risks when treating patients.
Topics: Humans; Female; Republic of Korea; Uterine Cervical Neoplasms; Papillomavirus Infections; Adult; Middle Aged; Human papillomavirus 16; Uterine Cervical Dysplasia; Cervix Uteri; Genotype; Cohort Studies; Aged; Papillomaviridae; Incidence
PubMed: 38918416
DOI: 10.1038/s41598-024-65056-7 -
Nature Communications Jun 2024Human T-cell leukemia virus type 1 (HTLV-1) infection is linked to the development of adult T-cell leukemia/lymphoma (ATLL) and the neuroinflammatory disease,...
Human T-cell leukemia virus type 1 (HTLV-1) infection is linked to the development of adult T-cell leukemia/lymphoma (ATLL) and the neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax oncoprotein regulates viral gene expression and persistently activates NF-κB to maintain the viability of HTLV-1-infected T cells. Here, we utilize a kinome-wide shRNA screen to identify the tyrosine kinase KDR as an essential survival factor of HTLV-1-transformed cells. Inhibition of KDR specifically induces apoptosis of Tax expressing HTLV-1-transformed cell lines and CD4 + T cells from HAM/TSP patients. Furthermore, inhibition of KDR triggers the autophagic degradation of Tax resulting in impaired NF-κB activation and diminished viral transmission in co-culture assays. Tax induces the expression of KDR, forms a complex with KDR, and is phosphorylated by KDR. These findings suggest that Tax stability is dependent on KDR activity which could be exploited as a strategy to target Tax in HTLV-1-associated diseases.
Topics: Humans; Gene Products, tax; Human T-lymphotropic virus 1; Vascular Endothelial Growth Factor Receptor-2; NF-kappa B; Paraparesis, Tropical Spastic; Cell Survival; Apoptosis; HTLV-I Infections; CD4-Positive T-Lymphocytes; T-Lymphocytes; Leukemia-Lymphoma, Adult T-Cell; Phosphorylation; HEK293 Cells
PubMed: 38918393
DOI: 10.1038/s41467-024-49737-5 -
PloS One 2024Danish women-who were HPV-vaccinated as girls-are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical... (Observational Study)
Observational Study
BACKGROUND
Danish women-who were HPV-vaccinated as girls-are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical cancer risk, we must reassess our screening strategies. We analyzed Danish HPV-vaccinated women's outcomes after the first screening test at age 23.
METHODS AND FINDINGS
Our study was embedded in Danish routine cytology-based screening. We conducted an observational study and included women born in 1994, offered the 4-valent HPV vaccine at age 14, and subsequently invited to screening at age 23. Cervical cytology was used for diagnostics and clinical management. Residual material was HPV tested with Cobas® 4800/6800. The most severe histology diagnosis within 795 days of screening was found through linkage with the Danish National Pathology Register. We calculated the number of women undergoing follow-up (repeated testing and/or colposcopy) per detected cervical intraepithelial neoplasia (CIN2+). A total of 6021 women were screened; 92% were HPV-vaccinated; 12% had abnormal cytology; 35% were high-risk HPV-positive, including 0.9% HPV16/18 positive, and 20% had follow-up. In women that were cytology-abnormal and HPV-positive (Cyt+/HPV+), 610 (98.5%) had been followed up, and 138 CIN2+ cases were diagnosed, resulting in 4.4 (95% CI 3.9-5.2) women undergoing follow-up per detected CIN2+. In contrast to recommendations, 182 (12.2%) cytology-normal and HPV-positive (Cyt-/HPV+) women were followed up within 795 days, and 8 CIN2+ cases were found, resulting in 22.8 (95% CI 13.3-59.3) women undergoing follow-up per detected CIN2+.
CONCLUSION
Overall, HPV prevalence was high in HPV-vaccinated women, but HPV16/18 had largely disappeared. In the large group of cytology-normal and HPV-positive women, 23 had been followed up per detected CIN2+ case. Our data indicated that primary HPV screening of young HPV-vaccinated women would require very effective triage methods to avoid an excessive follow-up burden.
TRIAL REGISTRATION
Trial registration number: NCT0304955.
Topics: Humans; Female; Denmark; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Papillomavirus Infections; Early Detection of Cancer; Young Adult; Cohort Studies; Uterine Cervical Dysplasia; Adult; Adolescent; Vaccination; Human papillomavirus 18; Mass Screening
PubMed: 38917143
DOI: 10.1371/journal.pone.0306044 -
NPJ Vaccines Jun 2024Gammaherpesviruses are oncogenic viruses that establish lifelong infections and are significant causes of morbidity and mortality. Vaccine strategies to limit...
Gammaherpesviruses are oncogenic viruses that establish lifelong infections and are significant causes of morbidity and mortality. Vaccine strategies to limit gammaherpesvirus infection and disease are in development, but there are no FDA-approved vaccines for Epstein-Barr or Kaposi sarcoma herpesvirus. As a new approach to gammaherpesvirus vaccination, we developed and tested a replication-deficient virus (RDV) platform, using murine gammaherpesvirus 68 (MHV68), a well-established mouse model for gammaherpesvirus pathogenesis studies and preclinical therapeutic evaluations. We employed codon-shuffling-based complementation to generate revertant-free RDV lacking expression of the essential replication and transactivator protein encoded by ORF50 to arrest viral gene expression early after de novo infection. Inoculation with RDV-50.stop exposes the host to intact virion particles and leads to limited lytic gene expression in infected cells yet does not produce additional infectious particles. Prime-boost vaccination of mice with RDV-50.stop elicited virus-specific neutralizing antibody and effector T cell responses in the lung and spleen. In contrast to vaccination with heat-inactivated WT MHV68, vaccination with RDV-50.stop resulted in a near complete abolishment of virus replication in the lung 7 days post-challenge and reduction of latency establishment in the spleen 16 days post-challenge with WT MHV68. Ifnar1 mice, which lack the type I interferon receptor, exhibit severe disease and high mortality upon infection with WT MHV68. RDV-50.stop vaccination of Ifnar1 mice prevented wasting and mortality upon challenge with WT MHV68. These results demonstrate that prime-boost vaccination with a gammaherpesvirus that is unable to undergo lytic replication offers protection against acute replication, impairs the establishment of latency, and prevents severe disease upon the WT virus challenge. Our study also reveals that the ability of a gammaherpesvirus to persist in vivo despite potent pre-existing immunity is an obstacle to obtaining sterilizing immunity.
PubMed: 38914546
DOI: 10.1038/s41541-024-00908-x -
Virology Journal Jun 2024We describe the case of a 57-year-old male with jaundice, abdominal distension and fatigue. He was diagnosed as chronic active Epstein-Barr virus infection (CAEBV) due...
We describe the case of a 57-year-old male with jaundice, abdominal distension and fatigue. He was diagnosed as chronic active Epstein-Barr virus infection (CAEBV) due to intermittent elevated liver enzymes, hepatosplenomegaly and pancytopenia, with persistent positive of EBV biomarkers in blood and also positive in liver tissue. The patient was reinfected by SARS-CoV-2 within 2 months companied with CAEBV. The patient's second infection with SARS-CoV-2 led to the aggravated liver dysfunction with pneumonia and re-admission. After receiving symptomatic treatment, the patient showed significantly improvement of symptoms with partially restoration of liver function. After discharge, the patient's health status continued to deteriorate and eventually died. The instances of SARS-CoV-2 co-infection with the original chronic virus are not uncommon, but the exact mechanism of EBV and SARS-CoV-2 coinfection and the relationship between them are still unclear. Since co-infection of SARS-CoV-2 with original chronic virus might affect each other and lead disease aggravated and complicated, it is necessary to differentiate in the diagnosis of disease and it is important to be aware of the re-infection signs of SARS-CoV-2 in people with chronic virus infection diseases, as well as the risk of co-infection of SARS-CoV-2 with other viruses.
Topics: Humans; Male; COVID-19; Epstein-Barr Virus Infections; Middle Aged; Reinfection; Coinfection; SARS-CoV-2; Herpesvirus 4, Human; Chronic Disease; Fatal Outcome
PubMed: 38910238
DOI: 10.1186/s12985-024-02418-7 -
Scientific Reports Jun 2024First-void urine (FVU) samples, containing human papillomavirus (HPV)-specific IgG from female genital tract secretions, provide a non-invasive option for disease...
First-void urine (FVU) samples, containing human papillomavirus (HPV)-specific IgG from female genital tract secretions, provide a non-invasive option for disease monitoring and vaccine impact assessment. This study explores the utility of FVU for IgG quantification, exploring stability and compatibility with DNA preservation methods, alongside various IgG enrichment methods. Healthy female volunteers provided FVU and serum samples. FVU was collected with or without urine conservation medium (UCM) and stored under different conditions before freezing at -80 °C. Four IgG enrichment methods were tested on FVU samples. All samples were analyzed using three total human IgG quantification assays and an in-house HPV16-specific IgG assay. Samples stored with UCM buffer had higher total and HPV16-specific IgG concentrations (p ≤ 0.01) and IgG remained stable for at least 14 days at room temperature. Among IgG enrichment methods, Amicon filtration (AM) and AM combined with Melon Gel purification (AM-MG) provided similar HPV16-IgG concentrations, correlating strongly with serum levels. Protein G magnetic beads methods were incompatible with time-resolved fluorescence-based assays. This study highlights FVU as a reliable and convenient sample for IgG quantification, demonstrating stability for at least 14 days at room temperature and compatibility with UCM DNA preservation. It emphasizes the need to select appropriate IgG enrichment methods and confirms the suitability of both AM and AM-MG methods, with a slightly better performance for AM-MG.
Topics: Humans; Female; Human papillomavirus 16; Immunoglobulin G; Adult; Antibodies, Viral; Papillomavirus Infections; Young Adult
PubMed: 38910149
DOI: 10.1038/s41598-024-65257-0 -
BMJ Open Jun 2024Sub-Saharan Africa (SSA) regions have the highest burden of cervical cancer (CC), accounting for nearly a quarter of global mortality. Many women in SSA are reluctant to...
INTRODUCTION
Sub-Saharan Africa (SSA) regions have the highest burden of cervical cancer (CC), accounting for nearly a quarter of global mortality. Many women in SSA are reluctant to access CC screening because they are uncomfortable exposing their private parts to healthcare providers. The perception of women who have experienced self-sampling in SSA is yet to be reviewed. This scoping review will explore the literature on the perception and attitude of women towards methods of collecting cervicovaginal samples for human papillomavirus (HPV) testing in SSA.
METHODS AND ANALYSIS
An extensive search using the Arksey and O'Malley framework will be conducted. The search criteria will be limited to original research conducted in community or clinical settings in SSA within the last 10 years. Four databases, namely, PUBMED, Cochrane, African Journals Online and Google Scholar, will be searched. Two independent persons (UIAB and DOO) will screen the titles and abstracts and later full texts using population, intervention, comparison and outcome criteria. IOMB will serve as a tiebreaker whenever there is no agreement on the choice of eligibility criteria. The screening process will be presented using Preferred Reporting Items for Systematic Reviews and Meta-Analyses for the scoping review flow format. The descriptive analysis of eligible studies for scoping reviews will be summarised. We will describe themes of attitude and perception covering pain, embarrassment, privacy and comfortability, willingness to self-sample, anxiety and confidence.
ETHICS AND DISSEMINATION
This is a scoping review protocol and does not require ethical approval. Findings from this review will be disseminated through peer-reviewed publications, the production of policy briefs, and presentations at local and international conferences.
Topics: Humans; Female; Africa South of the Sahara; Papillomavirus Infections; Uterine Cervical Neoplasms; Specimen Handling; Research Design; Early Detection of Cancer; Vaginal Smears; Papillomaviridae; Review Literature as Topic; Mass Screening; Human Papillomavirus Viruses
PubMed: 38910004
DOI: 10.1136/bmjopen-2024-085408 -
Nature Communications Jun 2024Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV,...
Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials.
Topics: Animals; Epstein-Barr Virus Infections; Antibodies, Neutralizing; Herpesvirus 4, Human; Humans; Female; Mice; Antibodies, Viral; Glycoproteins; Nanoparticles; Adjuvants, Immunologic; Lymphoma; Nanovaccines
PubMed: 38906867
DOI: 10.1038/s41467-024-49546-w -
Frontiers in Public Health 2024Persistent HR-HPV causes cervical cancer, exhibiting geographic variance. Europe/Americas have higher HPV16/18 rates, while Asia/Africa predominantly have non-16/18...
BACKGROUND
Persistent HR-HPV causes cervical cancer, exhibiting geographic variance. Europe/Americas have higher HPV16/18 rates, while Asia/Africa predominantly have non-16/18 HR-HPV. This study in Fujian, Asia, explores non-16/18 HR-HPV infections, assessing their epidemiology and cervical lesion association for targeted prevention.
METHODS
A total of 101,621 women undergoing HPV screening at a hospital in Fujian Province from 2013 to 2019 were included. HPV genotyping was performed. A subset of 11,666 HPV-positive women with available histopathology results were analyzed to characterize HPV genotype distribution across cervical diagnoses.
RESULTS
In 101,621 samples, 24.5% tested positive for HPV. Among these samples, 17.3% exhibited single infections, while 7.2% showed evidence of multiple infections. The predominant non-16/18 high-risk HPV types identified were HPV 52, 58, 53, 51, and 81. Single HPV infections accounted for 64.1% of all HPV-positive cases, with 71.4% of these being non-16/18 high-risk HPV infections. Age-related variations were observed in 11,666 HPV-positive patients with pathological results. Cancer patients were older. In the cancer group, HPV52 (21.8%) and HPV58 (18.6%) were the predominant types, followed by HPV33, HPV31, and HPV53. Compared to single HPV16/18 infection, non-16/18 HPV predominated in LSIL. Adjusted odds ratios (OR) for LSIL were elevated: multiple HPV16/18 (OR 2.18), multiple non-16/18 HR-HPV (OR 2.53), and multiple LR-HPV (OR 2.38). Notably, solitary HPV16/18 conferred higher odds for HSIL and cancer.
CONCLUSION
Our large-scale analysis in Fujian Province highlights HPV 52, 58, 53, 51, and 81 as predominant non-16/18 HR-HPV types. Multiple HPV poses increased LSIL risks, while solitary HPV16/18 elevates HSIL and cancer odds. These findings stress tailored cervical cancer prevention, highlighting specific HPV impacts on lesion severity and guiding region-specific strategies for optimal screening in Asia, emphasizing ongoing surveillance in the vaccination era.
Topics: Humans; Female; Papillomavirus Infections; Middle Aged; Adult; China; Uterine Cervical Neoplasms; Genotype; Papillomaviridae; Aged; Early Detection of Cancer; Human papillomavirus 18
PubMed: 38903575
DOI: 10.3389/fpubh.2024.1357073