The L1 protein serves as the principal capsid component of human papillomavirus (HPV). All globally commercialized HPV vaccines utilize virus-like particles (VLPs) formed through L1 protein self-assembly. Quantitative analysis of L1 protein concentration constitutes a critical parameter for evaluating the antigenic potency of HPV vaccines. In this study, we developed a chemiluminescent enzyme immunoassay (CLEIA) for precise quantification of L1 protein in bivalent HPV vaccines. Employing a sandwich immunoassay format, antigen-antibody complexes were immobilized on 96-well microplates using capture antibodies, followed by detection with HRP-conjugated secondary antibodies. Chemiluminescent signal amplification was achieved through enzymatic catalysis of luminol/hydrogen peroxide in the presence of enhancer molecules. Systematic optimization of experimental parameters yielded a validated methodology demonstrating excellent reproducibility (inter-assay CV < 4 %), accuracy (recovery rate 100.5 ± 2.8 % for 16L1 and 95.5 ± 6.4 % for 18L1), precision (inter-assay CV < 7 %) and sensitivity (limit of quantitation (LOQ) 0.0996 μg/mL for HPV16L1 and 0.1459 μg/mL for HPV18L1). This optimized assay provides a reliable analytical platform for quantitating L1 Protein in bivalent HPV vaccine.

Helicobacter pylori (H. pylori) is a known risk factor for gastric cancer, possibly via the PD-1/L1 pathway, and this infection may reduce the efficacy of immune checkpoint inhibitors (ICIs). This study explored the effects of H. pylori infection status on survival outcomes in patients with gastric cancer.

This single-center, retrospective study included patients with gastric adenocarcinoma between June 1985 and August 2022. Patients with different histological subtypes were excluded. Primary variables of interest included H. pylori infection status and treatment with ICIs. Other clinical information included demographics, cancer histology, the presence of other cancers, and vital status.

A total of 2930 patients were included, of whom 206 (7.0%) received ICIs, 196 (6.7%) had prior H. pylori infection, and 1037 (35.4%) had a diffuse subtype. Diffuse cancer subtypes were associated with better survival (P<0.05) at 3 and 5 years compared to intestinal-type adenocarcinomas. Diffuse cancers demonstrated better survival outcomes than intestinal cancers at 10 years, but only among H. pylori-positive patients (P=0.013). H. pylori positivity was associated with worse survival at 3 years (P=0.041) among patients taking ICIs, but not in those not receiving ICIs (P=0.325).

These findings suggest H. pylori infection may be an obstacle to successful immunotherapy, and may interact with cancer subtypes to differentially impact survival. Future studies are needed to validate the potential prognostic value of H. pylori positivity in gastric cancer.

Oral Cancer is one of the most prevalent malignant tumors of the head and neck. The three primary clinical treatments available till now for oral cancer are chemotherapy, radiation, and surgery. The goal of this review was to outline the basic principles of immunotherapy along with various immunotherapeutic agents on Oral Squamous Cell Carcinoma.

A comprehensive search in PubMed, Scopus, and Google Scholar was performed using relevant keywords. All the articles, both English as well as non-English were included also with inclusion data from high-incidence countries (South-east Asia) and the compilation was ten done after getting the data reviewed from two pathologists who were blinded to the data.

All the data has been compiled and the various sections in the manuscript provides an insight into the current trends in immunotherapy.

Advanced research studies are needed to counteract the hurdles associated with immunotherapy so that a greater proportion of patients can be treated.

One of the more recent developments that is promising is immunotherapy, which can be quite beneficial when used as a monotherapy or an adjuvant treatment. This more recent treatment approach could serve as the fourth pillar in cancer care, alongside radiation, chemotherapy, and surgery. Because immunotherapy relies on the patient's immunological environment, careful patient selection is essential to its effectiveness.

KRAS was (Kirsten rat sarcoma viral oncogene homolog) revealed as an important target in current therapeutic cancer research because alteration of RAS (rat sarcoma viral oncogene homolog) protein has a critical role in malignant modification, tumor angiogenesis, and metastasis. For cancer treatment, designing competitive inhibitors for this attractive target was difficult. Nevertheless, computational investigations of the protein's dynamic behavior displayed the existence of temporary pockets that could be used to design allosteric inhibitors. The last decade witnessed intensive efforts to discover KRAS inhibitors. In 2021, the first KRAS G12C covalent inhibitor, AMG 510, received FDA (Food and drug administration) approval as an anticancer medication that paved the path for future treatment strategies against this target. Computer-aided drug designing discovery has long been used in drug development research targeting different KRAS mutants. In this review, the major breakthroughs in computational methods adapted to discover novel compounds for different mutations have been discussed. Undoubtedly, virtual screening and molecular dynamic (MD) simulation and molecular docking are the most considered approach, producing hits that can be employed in subsequent refinements. After comprehensive analysis, Afatinib and Quercetin were computationally identified as hits in different publications. Several authors conducted covalent docking studies with acryl amide warheads groups containing inhibitors. Future studies are needed to demonstrate their true potential. In-depth studies focusing on various allosteric pockets demonstrate that the switch I/II pocket is a suitable site for drug designing. In addition, machine learning and deep learning based approaches provide new insights for developing anti-KRAS drugs. We believe that this review provides extensive information to researchers globally and encourages further development in this particular area of research.

Kaposi Sarcoma (KS) is a complex tumor caused by KS-associated herpesvirus 8 (KSHV). Histological analysis reveals a mixture of "spindle cells", vascular-like spaces, extravasated erythrocytes, and immune cells. In order to elucidate the infected and uninfected cell types in KS tumors, we examined twenty-five skin and blood samples from sixteen subjects by single cell RNA sequence analyses. Two populations of KSHV-infected cells were identified, one of which represented a CD34-negative proliferative fraction of endothelial cells, and the second representing CD34-positive cells expressing endothelial genes found in a variety of cell types including high endothelial venules, fenestrated capillaries, and endothelial tip cells. Although both infected clusters contained cells expressing lytic and latent KSHV genes, the CD34+ cells expressed more K5 and less K12. Novel cellular biomarkers were identified in the KSHV infected cells, including the sodium channel SCN9A. The number of KSHV positive cells was found to be less than 10% of total tumor cells in all samples and correlated inversely with tumor-infiltrating immune cells. T-cell receptor clones were expanded in KS tumors and blood, although in differing magnitudes. Changes in cellular composition in KS tumors after treatment with antiretroviral therapy alone, or immunotherapy were noted. These studies demonstrate the feasibility of single cell analyses to identify prognostic and predictive biomarkers.

Virion Infectivity Factor (Vif) of the Human Immunodeficiency Virus type 1 (HIV-1) targets and degrades cellular APOBEC3 proteins, key regulators of intrinsic and innate antiretroviral immune responses, thereby facilitating HIV-1 infection. While Vif's role in degrading APOBEC3G is well-studied, Vif is also known to cause cell cycle arrest, but the detailed nature of Vif's effects on the cell cycle has yet to be delineated. In this study, we employed high-temporal resolution single-cell live imaging and super-resolution microscopy to monitor individual cells during Vif-induced cell cycle arrest. Our findings reveal that Vif does not affect the G2/M boundary as previously thought. Instead, Vif triggers a unique and robust pseudo-metaphase arrest, distinct from the mild prometaphase arrest induced by Vpr. During this arrest, chromosomes align properly and form the metaphase plate, but later lose alignment, resulting in polar chromosomes. Notably, Vif, unlike Vpr, significantly reduces the levels of both Protein Phosphatase 1 (PP1) and 2 A (PP2A) at kinetochores, which regulate chromosome-microtubule interactions. These results unveil a novel role for Vif in kinetochore regulation that governs the spatial organization of chromosomes during mitosis.

This comprehensive review delves into the intricate role of programmed cell death in Epstein-Barr virus (EBV)-associated malignancies, focusing on the sophisticated interplay between viral mechanisms and the host's immune response. The central objective is to unravel how EBV exerts control over cell death pathways such as apoptosis, ferroptosis, and autophagy, thereby fostering its persistence and oncogenic potential. By dissecting these mechanisms, the review seeks to identify therapeutic strategies that could disrupt EBV's manipulation of these pathways, enhancing immune recognition and opening new avenues for targeted treatment. A deeper understanding of the molecular underpinnings of EBV's influence on cell death not only enriches the field of viral oncology but also pinpoints targets for drug development. Furthermore, the insights gleaned from this review could catalyze the design of vaccines aimed at preventing EBV infection or curtailing its oncogenic impact. Innovatively, the review synthesizes recent discoveries on the multifaceted roles of non-coding RNAs and cellular signaling pathways in modulating cell death within the context of EBV infection. By consolidating current knowledge and identifying areas where understanding is lacking, it lays the groundwork for future research that could lead to significant advancements in vaccine development and therapeutic interventions for EBV-related cancers. This review underscores the critical necessity for ongoing investigation into the complex interplay between EBV and host cell death mechanisms, with the ultimate goal of enhancing patient outcomes in EBV-associated diseases.

The resemblance between fallopian tube cells and serous borderline ovarian tumors (BOTs) suggests a potential origin link, with salpingitis proposed as a contributing factor in the pathogenesis of BOT. This study aimed to explore the potential association between pelvic inflammatory disease (PID) and the risk of developing BOT. A national population-based case-control study in Sweden included women with BOT between 1999 and 2020 and 10 matched controls. Data from nationwide registers were analyzed using conditional logistic regression, adjusting for age, residential district, educational level and parity. Among 4782 cases and 45,167 controls, 2.0% of cases and 1.3% of controls had a history of PID. Previous PID was associated with an increased risk of BOT overall (aOR, 1.48; 95% CI, 1.19-1.85). Significant association was observed with serous tumors (aOR, 1.76; 95% CI, 1.36-2.29), while not with mucinous tumors (aOR, 0.95; 95% CI, 0.60-1.49). A dose-response relationship between number of PID episodes and serous BOT risk was noted (Ptrend < .001). This study demonstrates that PID is associated with increased risk of serous BOT, with a dose response relationship. The study highlights the potential serious implications of upper reproductive tract infections and inflammation. This underscores the need for further investigation of biological mechanisms and possible impact of PID on serous BOT development.

Epstein-Barr virus (EBV) establishes persistent infection, causes infectious mononucleosis, is a major trigger for multiple sclerosis and contributes to multiple cancers. Yet, knowledge remains incomplete about how the virus remodels host B cells to support lytic replication. We previously identified that EBV lytic replication results in selective depletion of plasma membrane (PM) B cell receptor (BCR) complexes, composed of immunoglobulin and the CD79A and CD79B signaling chains. Here, we used proteomic and biochemical approaches to identify that the EBV early lytic protein BALF0/1 is responsible for EBV lytic cycle BCR degradation. Mechanistically, an immunoglobulin heavy chain (HC) cytoplasmic tail KVK motif was required for ubiquitin-mediated BCR degradation, while CD79A and CD79B were dispensable. BALF0/1 subverted caveolin-mediated endocytosis to internalize PM BCR complexes and to deliver them to the endoplasmic reticulum. BALF0/1 stimulated immunoglobulin HC cytoplasmic tail ubiquitination, which together with the ATPase valosin-containing protein/p97 drove ER-associated degradation of BCR complexes by cytoplasmic proteasomes. BALF0/1 knockout reduced the viral load of secreted EBV particles from B cells that expressed a monoclonal antibody against EBV glycoprotein 350 but not a control anti-influenza hemagglutinin antibody and increased viral particle immunoglobulin incorporation. Consistent with downmodulation of PM BCR, BALF0/1 overexpression reduced viability of a diffuse large B cell lymphoma cell line whose survival is dependent upon BCR signaling. Collectively, our results suggest that EBV BALF0/1 downmodulates immunoglobulin upon lytic reactivation to block BCR signaling and support virion release, but await the development of suitable models to test its roles in EBV reactivation in vivo.

A substantial portion of gastric cancer (GC) is linked to Epstein-Barr virus (EBV) infection. The characteristics of this viral genome, such as specific viral strains and large structural variations, influence the progression of diseases like nasopharyngeal carcinoma and hematological malignancy. However, the EBV genomes from GC have not been thoroughly characterized.

Our study involved 849 consecutive GC patients diagnosed at Nagoya City University Hospital, Japan (NCU cohort). We detected EBV from formalin-fixed, paraffin-embedded sections using a novel direct PCR-based rapid detection method. Additionally, we analyzed 142 EBV whole genomes (125 newly sequenced) from GC, comparing them with 205 genomes from other EBV-associated diseases.

We identified 32 (3.8%) patients associated with EBVaGC in the NCU cohort. Moreover, the direct PCR identified several GC specimens containing EBV-infected lymphocytes or their follicles. The dominant viral strain in GC was type 1 EBV, prevalent in most parts of the world, and no GC-specific strain was identified. We found no significant associations between single-nucleotide variants in the viral genome and GC. Structural variations of the EBV genome were infrequent in GC (4 cases, 2.1%), contrasting with EBV-associated hematological malignancy, which frequently carries large deletions.

This study is the first to uncover the genomic variations of EBV in GC. While EBV is definitively linked to GC, the characteristics of its genomes do not strongly correlate with disease development or progression. Our findings on viral genomes supplement the current understanding of human genomes in EBVaGC.

Colorectal cancer (CRC) is considered a widespread cancer, ranking second in mortality and incidence among cancer patients worldwide. CRC develops from adenoma to carcinoma through the dynamic interplay of genetic and environmental factors. The conventional modes of treatment, including operation, chemotherapy, and irradiation, are associated with significant challenges, such as drug resistance and toxicity, necessitating the exploration of new treatment modalities. These difficulties reveal the necessity of the emergence of new therapeutic approaches. This review mainly emphasizes the bacterial-based therapies that have recently developed like the engineered bacteriophage therapy and bacterial immunotherapy that pale the existing chemotherapy in terms of toxicity but are effective in killing tumor cells. Also, it also investigates various molecular genetic engineering strategies such as CRISPR-Cas9, CRISPR prime editing and gene silencing to achieve better targeting of CRC. Implementing these new approaches into the forefront of CRC treatment may bring better, more effective therapy with fewer side effects on patients' quality of life.

Viral infection plays a significant role in the development and progression of many cancers. Certain viruses, such as Human Papillomavirus (HPV), Epstein-Barr Virus (EBV), and Hepatitis B and C viruses (HBV, HCV), are well-known for their oncogenic potential. These viruses can dysregulate specific molecular and cellular processes through complex interactions with host cellular mechanisms. One such interaction involves a family of DNA mutators known as APOBEC3 (Apolipoprotein B mRNA Editing Catalytic Polypeptide-like 3). The primary function of these cytidine deaminases is to provide protection against viral infections by inducing viral mutagenesis. However, induction and dysregulation of A3 enzymes, driven by viral infection, can inadvertently lead to cellular DNA tumorigenesis. This review focuses on the current knowledge regarding the interplay between viral infection, A3 dysregulation, and cancer, highlighting the molecular mechanisms underlying this relationship.

Virion Infectivity Factor (Vif) of the Human Immunodeficiency Virus type 1 (HIV-1) targets and degrades cellular APOBEC3 proteins, key regulators of intrinsic and innate antiretroviral immune responses, thereby facilitating HIV-1 infection. While Vif's role in degrading APOBEC3G is well-studied, Vif is also known to cause cell cycle arrest, but the detailed nature of Vif's effects on the cell cycle has yet to be delineated. In this study, we employed high-temporal single-cell live imaging and super-resolution microscopy to monitor individual cells during Vif-induced cell cycle arrest. Our findings reveal that Vif does not affect the G2/M boundary as previously thought. Instead, Vif triggers a unique and robust pseudo-metaphase arrest, distinct from the mild prometaphase arrest induced by Vpr. During this arrest, chromosomes align properly and form the metaphase plate, but later lose alignment, resulting in polar chromosomes. Notably, Vif, unlike Vpr, significantly reduces the levels of both Protein Phosphatase 1 (PP1) and 2A (PP2A) at kinetochores, which regulate chromosome-microtubule interactions. These results unveil a novel role for Vif in kinetochore regulation that governs the spatial organization of chromosomes during mitosis.

The connection between microbial infections and tumor formation is notably exemplified by Helicobacter pylori (H. pylori) and its association with gastric cancer (GC) and colorectal cancer (CRC). While early studies hinted at a link between H. pylori and colorectal neoplasms, comprehensive retrospective cohort studies were lacking. Recent research indicates that individuals treated for H. pylori infection experience a significant reduction in both CRC incidence and mortality, suggesting a potential role of this infection in malignancy development. Globally, H. pylori prevalence varies, with higher rates in developing countries (80-90%) compared to developed nations (20-50%). This infection is linked to chronic gastritis, peptic ulcers, and GC, highlighting the importance of understanding its epidemiology for public health interventions. H. pylori significantly increases the risk of non-cardia GC. Some meta-analyses have shown a 1.49-fold increased risk for colorectal adenomas and a 1.70-fold increase for CRC in infected individuals. Additionally, H. pylori eradication may lower the CRC risk, although the relationship is still being debated. Although eradication therapy shows promise in reducing GC incidence, concerns about antibiotic resistance pose treatment challenges. The role of H. pylori in colorectal tumors remains contentious, with some studies indicating an increased risk of colorectal adenoma, while others find minimal association. Future research should investigate the causal mechanisms between H. pylori infection and colorectal neoplasia, including factors like diabetes, to better understand its role in tumor formation and support widespread eradication efforts to prevent both gastric and colorectal cancers.

Helicobacter pylori (H. pylori) infection is widely acknowledged as the primary risk factor for gastric cancer, facilitating its progression via the Correa cascade. Concurrently, Hexokinase Domain Containing 1 (HKDC1) has been implicated in the mediation of aerobic glycolysis, contributing to tumorigenesis across various cancers. However, the precise role of HKDC1 in the inflammatory transformation associated with H. pylori-induced gastric cancer remains elusive. In this study, transcriptome sequencing revealed a significant correlation between HKDC1 and H. pylori-induced gastric cancer. Subsequent validation using qRT-PCR, immunohistochemistry, and Western blot analysis confirmed elevated HKDC1 expression in both human and murine gastritis and gastric tumors. Moreover, in vitro and in vivo experiments demonstrated that H. pylori infection up-regulates TGF-β1 and p-Smad2, thereby activating the epithelial-mesenchymal transition (EMT) pathway, with HKDC1 playing a pivotal role. Suppression of HKDC1 expression or pharmacological inhibition of TGF-β1 reversed EMT activation, consequently reducing gastric cancer cell proliferation and metastasis. These results underscore HKDC1's essential contribution to H. pylori-induced gastric cancer progression via EMT activation.

Nasopharyngeal carcinoma (NPC) is a neoplasm related to inflammation; the expression of cytokines, such as CCL3, CCL4, CCL20, IL-1α, IL-1β, IL-6, IL-8, and IL-10, among others, is presumed to be associated with NPC occurrence and development. Therefore, the circulating levels of these cytokines may be potential biomarkers for assessing tumor aggressiveness, exploring cellular interactions, and monitoring tumor therapeutic responses. Numerous scholars have comprehensively explored the putative mechanisms through which these inflammatory factors affect NPC progression and therapeutic responses. Moreover, investigations have focused on elucidating the correlation between the systemic levels of these cytokines and the incidence and prognosis of NPC. This comprehensive review aims to delineate the advancements in research concerning the relationship between inflammatory factors and NPC while considering their prospective roles as novel prognostic and predictive biomarkers in the context of NPC.

Cancers account for many deaths worldwide and natural compounds and their derivatives are interesting chemotherapeutic agents for cancer drug development. In this study, a natural compound 3,3'4-trimethoxy-4'-rutinosylellagic acid (TR2) and its acetylated derivative 3,3'4-trimethoxy-4'-hexaacetylrutinosylellagic acid (TR22) were evaluated for their antioxidant and anticancer effects against estrogen sensitive (MCF-7) and estrogen non-sensitive (MDA-MB 231) breast adenocarcinoma. In the β-Carotene-linoleic acid assay, DPPH• radical scavenging and CUPRAC assay, the compound TR2 had better activity than the standard α-Tocopherol, while in the ABTS•+ assay, it was more active than both standards α- α-Tocopherol and BHA. Both compounds had good antioxidant effects with TR2 being more active than TR22. Both compounds inhibited growth of breast carcinoma cells when compared to the untreated controls after 72 h. Compound TR22 significantly (p < 0.001) inhibited proliferation of both MCF-7 and MDA-MB 231 breast carcinoma cell lines suggesting that acetylation reaction improves inhibition of breast cancer cells growth. On the contrary, TR2 exhibited better inhibitory effect of clone formation than TR22 suggesting that acetylation reduces the activity in this assay. Both compounds inhibited migration of the cancer cells when compared to the untreated control cells and compound TR2 exhibited greater cellular anti-migration effect than TR22 at the same concentration and after the same period of incubation. Molecular docking studies supplemented the results and revealed that TR2 and TR22 had appreciable interactions with tyrosine kinase with negative binding energies suggesting that they are potent receptor tyrosine kinase inhibitors which can impede on cancer progression.

The tumor microenvironment (TME) can be regarded as a complex and dynamic microecosystem generated by the interactions of tumor cells, interstitial cells, the extracellular matrix, and their products and plays an important role in the occurrence, progression and metastasis of tumors. In a previous study, we constructed an IEO model (prI-, prE-, and pOst-metastatic niche) according to the chronological sequence of TME development. In this paper, to fill the theoretical gap in spatial heterogeneity in the TME, we defined an MCIB model (Metabolic, Circulatory, Immune, and microBial microenvironment). The MCIB model divides the TME into four subtypes that interact with each other in terms of mechanism, corresponding to the four major links of metabolic reprogramming, vascular remodeling, immune response, and microbial action, providing a new way to assess the TME. The combination of the MCIB model and IEO model comprehensively depicts the spatiotemporal evolution of the TME and can provide a theoretical basis for the combination of clinical targeted therapy, immunotherapy, and other comprehensive treatment modalities for tumors according to the combination and crosstalk of different subtypes in the MCIB model and provide a powerful research paradigm for tumor drug-resistance mechanisms and tumor biological behavior.

Cumulative evidence attests to the essential roles of commensal microbes in the physiology of hosts. Although the microbiome has been a major research subject since the time of Luis Pasteur and William Russell over 140 years ago, recent findings that certain intracellular bacteria contribute to the pathophysiology of healthy vs. diseased tissues have brought the field of the microbiome to a new era of investigation. Particularly, in the field of breast cancer research, breast-tumor-resident bacteria are now deemed to be essential players in tumor initiation and progression. This is a resurrection of Russel's bacterial cause of cancer theory, which was in fact abandoned over 100 years ago. This review will introduce some of the recent findings that exemplify the roles of breast-tumor-resident microbes in breast carcinogenesis and metastasis and provide mechanistic explanations for these phenomena. Such information would be able to justify the utility of breast-tumor-resident microbes as biomarkers for disease progression and therapeutic targets.

Hepatitis B infection due to poor practices can result in prolonged hospital stays, long-term disability, increased microbial resistance, financial burdens and death. There has been no comprehensive study assessing the practice level of hepatitis B virus infection prevention in Ethiopia despite the high risk of exposure. Thus, this review aimed to assess practice on hepatitis B virus infection prevention in Ethiopia.

For published studies, we conducted a thorough search of the PubMed, African Journal Online, Science Direct, Cochrane Library and Google Scholar databases. The data were exported to STATA version 11 (STATA Corp LLC) for meta-analysis. Heterogeneity between the results of the primary studies was assessed using Cochran's Q chi-square test and quantified with I2 statistics. A random effect model, specifically the DerSimonian and Laird pooled estimate method, was used due to the presence of heterogeneity between the included articles.

Initially, 1738 articles were retrieved through electronic database searching. Of these, 910 were from Google Scholar, 4 from PubMed, 378 from Science Direct, 421 from African Journal Online and 25 from the Cochrane Library. The pooled estimate showed that 41.54% (95% CI: 33.81-49.27, P < 0.001) of individuals had a good practice towards hepatitis B virus infection prevention. Good knowledge of HBV infection prevention (POR = 1.13, 95% CI: (0.28-4.46) and urban residence (POR = 4.27, 95% CI: 1.17-15.49) were factors significantly associated with practices aimed at preventing hepatitis B virus infection. Based on the findings of the current study, most of the participants reported poor practices for hepatitis B virus infection prevention. Residence and knowledge of hepatitis B virus prevention were significantly associated with practices aimed at preventing hepatitis B virus infection. The Ministry of Health should collaborate with the health bureau for continual awareness about the mode of transmission and preventive measures of HBV.

Background The preparation of multidisciplinary team (MDT) meetings can be time-consuming. In addition to the clinical data being available digitally in subsystems, the preparation of more complex cases requires literature research. Several expert systems have been developed to support this process. However, the interaction with these systems has to be trained. Current development enables linguistic interaction with such artificial intelligence (AI) systems. To the best of our knowledge, these have not been tested as premedical screening tools for MDT. Methods This is a retrospective consecutive case series of 10 cervical cancer cases comparing the medical recommendations of the MDT and artificial intelligence (AI) on a low level (i.e., surgery, systemic treatment, and radiotherapy). Results The clinical cases ranged from primary diagnosis via suspected recurrence to palliative settings. The AI repeatedly stated that medical professionals need to be consulted before treatment decisions. The AI answers ranged from no agreement to overachievement by mentioning treatment options for preexisting risk factors (such as obesity). In standard cases, the AI answer matched well with the expert recommendations. In some cases, the AI answers were contrary to our treatment recommendation. Conclusion The interaction with current language AIs is temptingly easy, and the replies are very understandable. Despite the AI warning regarding medical recommendations in the majority of our cases, there was a good match with the MDT recommendations. However, in some cases, the medical evidence behind the answers was missing or in the worst case fictional. In our case series, the AI did not meet the requirements to support a clinical MDT meeting by prescreening the therapeutic options. However, it did exceed the expectations regarding the risk factors of the patients.

The human leukocyte antigen (HLA) region plays an important role in human health through involvement in immune cell recognition and maturation. While genetic variation in the HLA region is associated with many diseases, the pleiotropic patterns of these associations have not been systematically investigated. Here, we developed a haplotype approach to investigate disease associations phenome-wide for 412,181 Finnish individuals and 2,459 traits. Across the 1,035 diseases with a GWAS association, we found a 17-fold average per-SNP enrichment of hits in the HLA region. Altogether, we identified 7,649 HLA associations across 647 traits, including 1,750 associations uncovered by haplotype analysis. We find some haplotypes show trade-offs between diseases, while others consistently increase risk across traits, indicating a complex pleiotropic landscape involving a range of diseases. This study highlights the extensive impact of HLA variation on disease risk, and underscores the importance of classical and non-classical genes, as well as non-coding variation.

T cells are essential tumor suppressors in cancer immunology, but their dysfunction induced by cancer cells can result in T cell exhaustion. Exhausted T cells (Tex) significantly influence the tumor immune environment, and thus, there is a need for their thorough investigation across different types of cancer. Here, we address the role of Tex cells in pan-cancer, focusing on the expression, mutations, methylation, immune infiltration, and drug sensitivity of a molecular signature comprising of the genes HAVCR2, CXCL13, LAG3, LAYN, TIGIT, and PDCD1across multiple cancer types, using bioinformatics analysis of TCGA data. Our analysis revealed that the Tex signature genes are differentially expressed across 14 cancer types, being correlated with patient survival outcomes, with distinct survival trends. Pathway analysis indicated that the Tex genes influence key cancer-related pathways, such as apoptosis, EMT, and DNA damage pathways. Immune infiltration analysis highlighted a positive correlation between Tex gene expression and immune cell infiltration in bladder cancer, while mutations in these genes were associated with specific immune cell enrichments in UCEC and SKCM. CNVs in Tex genes were widespread across cancers. We also highlight high LAYN methylation in most tumors and a negative correlation between methylation levels and immune cell infiltration in various cancers. Drug sensitivity analysis identified numerous correlations, with CXCL13 and HAVCR2 expressions influencing sensitivity to several drugs, including Apitolisib, Belinostat, and Docetaxel. Overall, these findings highlight the importance of reviving exhausted T cells to enhance the treatment efficacy to significantly boost anti-tumor immunity and achieve better clinical outcomes.

This study explores the pharmacological potential of chalcones through a multidisciplinary approach, including synthesis, quantum theory, molecular electrostatics, and density functional theory (DFT) calculations. The synthesized compound, analyzed via single crystal X-ray diffraction, crystallized in the triclinic system (space group P-1) with C-H⋯O interactions stabilizing its structure. Hirshfeld surface analysis confirms these interactions, with H-H contacts dominating (45.1 %). Molecular electrostatics analysis reveals charge distribution, and a 3.10 eV HOMO-LUMO energy gap indicates bioactivity. Molecular docking identifies the compound (3a) showed a maximum Gscore of HTNF-α (-9.81 kcal/mol); Tubulin (-7.96 kcal/mol); COX2 (-7.88 kcal/mol), EGFR (-6.72 kcal/mol), and VEGFR1(-2.50 kcal/mol). Where compound (3c) showed maximum binding at the putative binding site with dock scores for VEGFR2 (-9.24 kcal/mol). This research not only advances molecular science but also holds promise for diverse applications, including drug design. The significance of this study lies in its comprehensive exploration of the pharmacological potential of chalcones using a multidisciplinary approach. Through the integration of synthesis, quantum theory, molecular electrostatics, and density functional theory (DFT) calculations, we have extensively explored the structural and biochemical characteristics of these compounds. This investigation has revealed valuable insights that have the potential to lead to significant advancements in the fields of molecular science and drug design. Moreover, the molecular docking studies shed light on the compound's interaction with various biological targets. The significant binding affinities observed for these targets underscore the potential therapeutic relevance of the synthesized compound in diverse disease conditions.

Gastric cancer (GC) poses notable economic and health burdens in settings where the incidence of disease is prevalent. Some countries have established early screening and treatment programs to address these challenges. The objectives of this systematic review were to summarize the cost-effectiveness of gastric cancer screening presented in the literature and to identify the critical factors that influence the cost-effectiveness of screening. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Economic evaluation studies of gastric cancer screening were reviewed from SCOPUS and PubMed. The Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) was used to assess the quality of reporting presented in the selected articles. Only primary economic evaluation studies addressing the cost-effectiveness, cost-utility, and cost-benefit of gastric cancer screening were selected. Two reviewers scrutinized the selected articles (title, abstract, and full text) to determine suitability for the systematic review based on inclusion and exclusion criteria. Authors' consensus was relied on where disagreements arose. The main outcome measures of concern in the systematic review were cost, effectiveness (as measured by either quality-adjusted life years (QALY) or life-years saved (LYS)), and incremental cost-effectiveness ratio (ICER) of screening versus either no screening or an alternative screening method. Thirty-one studies were selected for the final review. These studies investigated the cost-effectiveness of GC screening based on either primary, secondary, or a combination of primary and secondary interventions. The main primary intervention was Helicobacter pylori (Hp) screening with eradication, while the main secondary intervention was endoscopic screening. Cost-effectiveness was evaluated against no screening or screening using an alternative method in both observational and model-based studies. Screening was mainly cost-effective in Asian countries or their diasporas where the prevalence of GC was high. GC screening was generally not cost-effective among Western countries. GC screening can be cost-effective, but cost-effectiveness is dependent on context-specific factors, including geographical location, the prevalence of GC in the local population, and the screening tool adopted. However, there is benefit in targeting high-risk population groups in Asian countries and their diaspora for GC screening.

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk.

Human papillomavirus (HPV), a common cause of sexually transmitted diseases, may cause warts and lead to various types of cancers, which makes it important to understand the risk factors associated with it. HPV is the leading risk factor and plays a crucial role in the progression of cervical cancer. Viral oncoproteins E6 and E7 play a pivotal role in this process. Beyond cervical cancer, HPV-associated cancers of the mouth and throat are also increasing. HPV can also contribute to other malignancies like penile, vulvar, and vaginal cancers. Emerging evidence links HPV to these cancers. Research on the oncogenic effect of HPV is still ongoing and explorations of screening techniques, vaccination, immunotherapy and targeted therapeutics are all in progress. The present review offers valuable insight into the current understanding of the role of HPV in cancer and its potential implications for treatment and prevention in the future.

Kaposi sarcoma associated herpesvirus (KSHV) is associated with around 1% of all human tumors, including the B cell malignancy primary effusion lymphoma (PEL), in which co-infection with the Epstein Barr virus (EBV) can almost always be found in malignant cells. Here, we demonstrate that KSHV/EBV co-infection of mice with reconstituted human immune systems (humanized mice) leads to IgM responses against both latent and lytic KSHV antigens, and expansion of central and effector memory CD4+ and CD8+ T cells. Among these, KSHV/EBV dual-infection allows for the priming of CD8+ T cells that are specific for the lytic KSHV antigen K6 and able to kill KSHV/EBV infected B cells. This suggests that K6 may represent a vaccine antigen for the control of KSHV and its associated pathologies in high seroprevalence regions, such as Sub-Saharan Africa.

Epithelial cells adhere to a specialized extracellular matrix called the basement membrane which allows them to polarize and form epithelial tissues. The extracellular matrix provides essential physical scaffolding and biochemical and biophysical cues required for tissue morphogenesis, differentiation, function, and homeostasis. Epithelial cell adhesion to the extracellular matrix (i.e., basement membrane) plays a critical role in organizing epithelial tissues, separating the epithelial cells from the stroma. Epithelial cell detachment from the basement membrane classically results in death, though detachment or invasion through the basement membrane represents a critical step in carcinogenesis. Epithelial cells bind to the extracellular matrix via specialized matrix receptors, including integrins. Integrins are transmembrane receptors that form a mechanical linkage between the extracellular matrix and the intracellular cytoskeleton and are required for anchorage-dependent cellular functions such as proliferation, migration, and invasion. The role of integrins in the development, growth, and dissemination of multiple types of carcinomas has been investigated by numerous methodologies, which has led to great complexity. To organize this vast array of information, we have utilized the "Hallmarks of Cancer" from Hanahan and Weinberg as a convenient framework to discuss the role of integrins in the pathogenesis of cancers. This review explores this biology and how its complexity has impacted the development of integrin-targeted anti-cancer therapeutics.

Colorectal cancer (CRC) is a common malignant tumor that occurs in the colon. Gut microbiota is a complex ecosystem that plays an important role in the pathogenesis of CRC. Our previous studies showed that the soluble dietary fiber of foxtail millet (FMB-SDF) exhibited significant antitumor activity in vitro. The present study evaluated the anticancer potential of FMB-SDF in the azoxymethane (AOM)- and dextran sodium sulfate (DSS)-induced mouse CRC models. The results showed that FMB-SDF could significantly alleviate colon cancer symptoms in mice. Further, we found that FMB-SDF consumption significantly altered gut microbiota diversity and the overall structure and regulated the abundance of some microorganisms in CRC mice. Meanwhile, KEGG pathway enrichment showed that FMB-SDF can also alleviate the occurrence of colon cancer in mice by regulating certain cancer-related signaling pathways. In conclusion, our findings may provide a novel approach for the prevention and biotherapy of CRC.

In view of a large number of people infected with Helicobacter pylori (H. pylori) with great harm followed, there is an urgent need to develop a non-invasive, easy-to-operate, and rapid detection method, and to identify effective sterilization strategies. In this study, highly specific nanoprobes with nanozyme activity, Ag@Pt nanoparticles (NPs) with the antibody, were utilized as a novel lateral flow immunoassay (LFIA). The optical label (Ag@Pt NPs) was enhanced by the introduction of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) and compared with a gold nanoparticles (Au NPs) optical label. Under the optimal condition, Ag@Pt-LFIA and TMB-enhanced Ag@Pt-LFIA for H. pylori were successfully established, two of which were over twofold and 100-fold more sensitive than conventional visual Au NP-based LFIA, respectively. Furthermore, Ag@Pt NPs with the antibody irradiated with NIR laser (808 nm) at a power intensity of 550 mW/cm2 for 5 min exhibited a remarkable antibacterial effect. The nanoprobes could close to bacteria through effective interactions between antibodies and bacteria, thereby benefiting photothermal sterilization. Overall, Ag@Pt NPs provide promising applications in pathogen detection and therapeutic applications.

(1) Background: HBV-DNA is an essential clinical indicator of primary hepatocellular carcinoma (HCC) prognosis. Our study aimed to investigate the prognostic implication of a low load of HBV-DNA in HCC patients who underwent local treatment. Additionally, we developed and validated a nomogram to predict the recurrence of patients with low (20-100 IU/mL) viral loads (L-VL). (2) Methods: A total of 475 HBV-HCC patients were enrolled, including 403 L-VL patients and 72 patients with very low (<20 IU/mL) viral loads (VL-VL). L-VL HCC patients were randomly divided into a training set (N = 282) and a validation set (N = 121) at a ratio of 7:3. Utilizing the Lasso-Cox regression analysis, we identified independent risk factors for constructing a nomogram. (3) Results: L-VL patients had significantly shorter RFS than VL-VL patients (38.2 m vs. 23.4 m, p = 0.024). The content of the nomogram included gender, BCLC stage, Glob, and MLR. The C-index (0.682 vs. 0.609); 1-, 3-, and 5-year AUCs (0.729, 0.784, and 0.783, vs. 0.631, 0.634, the 0.665); calibration curves; and decision curve analysis (DCA) curves of the training and validation cohorts proved the excellent predictive performance of the nomogram. There was a statistically significant difference in RFS between the low-, immediate-, and high-risk groups both in the training and validation cohorts (p < 0.001); (4) Conclusions: Patients with L-VL had a worse prognosis. The nomogram developed and validated in this study has the advantage of predicting patients with L-VL.

Helicobacter pylori is a gastric oncopathogen that infects over half of the world's human population. It is a Gram-negative, microaerophilic, helix-shaped bacterium that is equipped with flagella, which provide high motility. Colonization of the stomach is asymptomatic in up to 90% of people but is a recognized risk factor for developing various gastric disorders such as gastric ulcers, gastric cancer and gastritis. Invasion of the human stomach occurs via numerous virulence factors such as CagA and VacA. Similarly, outer membrane proteins (OMPs) play an important role in H. pylori pathogenicity as a means to adapt to the epithelial environment and thereby facilitate infection. While some OMPs are porins, others are adhesins. The epithelial cell receptors SabA, BabA, AlpA, OipA, HopQ and HopZ have been extensively researched to evaluate their epidemiology, structure, role and genes. Moreover, numerous studies have been performed to seek to understand the complex relationship between these factors and gastric diseases. Associations exist between different H. pylori virulence factors, the co-expression of which appears to boost the pathogenicity of the bacterium. Improved knowledge of OMPs is a major step towards combatting this global disease. Here, we provide a current overview of different H. pylori OMPs and discuss their pathogenicity, epidemiology and correlation with various gastric diseases.

Kaposi Sarcoma (KS) is a complex tumor caused by KS-associated herpesvirus 8 (KSHV). Histological analysis reveals a mixture of "spindle cells", vascular-like spaces, extravasated erythrocytes, and immune cells. In order to elucidate the infected and uninfected cell types in KS tumors, we examined skin and blood samples from twelve subjects by single cell RNA sequence analyses. Two populations of KSHV-infected cells were identified, one of which represented a proliferative fraction of lymphatic endothelial cells, and the second represented an angiogenic population of vascular endothelial tip cells. Both infected clusters contained cells expressing lytic and latent KSHV genes. Novel cellular biomarkers were identified in the KSHV infected cells, including the sodium channel SCN9A. The number of KSHV positive tumor cells was found to be in the 6% range in HIV-associated KS, correlated inversely with tumor-infiltrating immune cells, and was reduced in biopsies from HIV-negative individuals. T-cell receptor clones were expanded in KS tumors and blood, although in differing magnitudes. Changes in cellular composition in KS tumors were identified in subjects treated with antiretroviral therapy alone, or immunotherapy. These studies demonstrate the feasibility of single cell analyses to identify prognostic and predictive biomarkers.

Kaposi sarcoma (KS) is a malignancy caused by the KS-associated herpesvirus (KSHV) that causes skin lesions, and may also be found in lymph nodes, lungs, gastrointestinal tract, and other organs in immunosuppressed individuals more commonly than immunocompetent subjects. The current study examined gene expression in single cells from the tumor and blood of these subjects, and identified the characteristics of the complex mixtures of cells in the tumor. This method also identified differences in KSHV gene expression in different cell types and associated cellular genes expressed in KSHV infected cells. In addition, changes in the cellular composition could be elucidated with therapeutic interventions.

The purpose of this study was to identify biomarkers associated with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and to develop a new combination with good diagnostic performance. This study was divided into four phases: discovery, verification, validation, and modeling. A total of four candidate tumor-associated autoantibodies (TAAb; anti-ZIC2, anti-PCNA, anti-CDC37L1, and anti-DUSP6) were identified by human proteome microarray (52 samples) and bioinformatics analysis. Subsequently, these candidate TAAbs were further confirmed by indirect ELISA with two testing cohorts (120 samples for verification and 663 samples for validation). The AUC for these four TAAbs to identify patients with HBV-HCC from chronic hepatitis B (CHB) patients ranged from 0.693 to 0.739. Finally, a diagnostic panel with three TAAbs (anti-ZIC2, anti-CDC37L1, and anti-DUSP6) was developed. This panel showed superior diagnostic efficiency in identifying early HBV-HCC compared with alpha-fetoprotein (AFP), with an AUC of 0.834 [95% confidence interval (CI), 0.772-0.897] for this panel and 0.727 (95% CI, 0.642-0.812) for AFP (P = 0.0359). In addition, the AUC for this panel to identify AFP-negative patients with HBV-HCC was 0.796 (95% CI, 0.734-0.858), with a sensitivity of 52.4% and a specificity of 89.0%. Importantly, the panel in combination with AFP significantly increased the positive rate for early HBV-HCC to 84.1% (P = 0.005) and for late HBV-HCC to 96.3% (P < 0.001). Our findings suggest that AFP and the autoantibody panel may be independent but complementary serologic biomarkers for HBV-HCC detection.

We developed a robust diagnostic panel for identifying patients with HBV-HCC from patients with CHB. This autoantibody panel provided superior diagnostic performance for HBV-HCC at an early stage and/or with negative AFP results. Our findings suggest that AFP and the autoantibody panel may be independent but complementary biomarkers for HBV-HCC detection.

Human Papillomaviruses (HPV) are a diverse family of non-enveloped dsDNA viruses that infect the skin and mucosal epithelia. Persistent HPV infections can lead to cancer frequently involving integration of the virus into the host genome, leading to sustained oncogene expression and loss of capsid and genome maintenance proteins. Microhomology-mediated double-strand break repair, a DNA double-stranded breaks repair pathway present in many organisms, was initially thought to be a backup but it's now seen as vital, especially in homologous recombination-deficient contexts. Increasing evidence has identified microhomology (MH) near HPV integration junctions, suggesting MH-mediated repair pathways drive integration. In this comprehensive review, we present a detailed summary of both the mechanisms underlying MH-mediated repair and the evidence for its involvement in HPV integration in cancer. Lastly, we highlight the involvement of these processes in the integration of other DNA viruses and the broader implications on virus lifecycles and host innate immune response.

Single-point mutations in the Kirsten rat sarcoma (KRAS) viral proto-oncogene are the most common cause of human cancer. In humans, oncogenic KRAS mutations are responsible for about 30% of lung, pancreatic, and colon cancers. One of the predominant mutant KRAS G12D variants is responsible for pancreatic cancer and is an attractive drug target. At the time of writing, no Food and Drug Administration (FDA) approved drugs are available for the KRAS G12D mutant. So, there is a need to develop an effective drug for KRAS G12D. The process of finding new drugs is expensive and time-consuming. On the other hand, in silico drug designing methodologies are cost-effective and less time-consuming. Herein, we employed machine learning algorithms such as K-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF) for the identification of new inhibitors against the KRAS G12D mutant. A total of 82 hits were predicted as active against the KRAS G12D mutant. The active hits were docked into the active site of the KRAS G12D mutant. Furthermore, to evaluate the stability of the compounds with a good docking score, the top two complexes and the standard complex (MRTX-1133) were subjected to 200 ns MD simulation. The top two hits revealed high stability as compared to the standard compound. The binding energy of the top two hits was good as compared to the standard compound. Our identified hits have the potential to inhibit the KRAS G12D mutation and can help combat cancer. To the best of our knowledge, this is the first study in which machine-learning-based virtual screening, molecular docking, and molecular dynamics simulation were carried out for the identification of new promising inhibitors for the KRAS G12D mutant.

Helicobacter pylori (H. pylori) infection is a known cause of many digestive diseases, including gastritis, peptic ulcers, and gastric cancer. However, the underlying mechanisms by which H. pylori infection triggers these disorders are still not clearly understood. Gastric cancer is a slow progressing disease, which makes it difficult to study. We have developed an accelerated disease progression mouse model, which leverages mice deficient in the myeloid differentiation primary response 88 gene (Myd88-/-) infected with Helicobacter felis (H. felis). Using this model and gastric biopsy samples from patients, we report that activation of the Toll/interleukin-1 receptor (TIR)-domain-containing adaptor inducing interferon-β (TRIF)-type I interferon (IFN-I) signaling pathway promotes Helicobacter-induced disease progression toward severe gastric pathology and gastric cancer development. Further, results implicated downstream targets of this pathway in disease pathogenesis. These findings may facilitate stratification of Helicobacter-infected patients and thus enable treatment prioritization of patients.

Glioblastoma (GB) is a lethal and aggressive brain tumour. While molecular characteristics of GB is studied extensively, the aetiology of GB remains uncertain. The interest in exploring viruses as a potential contributor to the development of GB stems from the notion that viruses are known to play a key role in pathogenesis of other human cancers such as cervical cancer. Nevertheless, the role of viruses in GB remains controversial.

This review delves into the current body of knowledge surrounding the presence of viruses in GB as well as provide updates on clinical trials examining the potential inclusion of antiviral therapies as part of the standard of care protocol.

The review summarises current evidences and important gaps in our knowledge related to the presence of viruses in GB.

Increasing evidence suggests the potential of Epstein-Barr virus (EBV) vaccination in preventing multiple sclerosis (MS). We aimed to explore the cost-effectiveness of a hypothetical EBV vaccination to prevent MS in an Australian setting.

A five-state Markov model was developed to simulate the incidence and subsequent progression of MS in a general Australian population. The model inputs were derived from published Australian sources. Hypothetical vaccination costs, efficacy and strategies were derived from literature. Total lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated for two hypothetical prevention strategies versus no prevention from the societal and health system payer perspectives. Costs and QALYs were discounted at 5% annually. One-way, two-way and probabilistic sensitivity analyses were performed.

From societal perspective, EBV vaccination targeted at aged 0 and aged 12 both dominated no prevention (ie, cost saving and increasing QALYs). However, vaccinating at age 12 was more cost-effective (total lifetime costs reduced by $A452/person, QALYs gained=0.007, ICER=-$A64 571/QALY gained) than vaccinating at age 0 (total lifetime costs reduced by $A40/person, QALYs gained=0.003, ICER=-$A13 333/QALY gained). The probabilities of being cost-effective under $A50 000/QALY gained threshold for vaccinating at ages 0 and 12 were 66% and 90%, respectively. From health system payer perspective, the EBV vaccination was cost-effective at age 12 only. Sensitivity analyses demonstrated the cost-effectiveness of EBV vaccination to prevent MS under a wide range of plausible scenarios.

MS prevention using future EBV vaccinations, particularly targeted at adolescence population, is highly likely to be cost-effective.