Endobronchial involvement by diffuse large B-cell lymphoma (DLBCL) is rare in children, particularly in the setting of Epstein–Barr virus (EBV)-associated lymphoproliferation. We report an 8-year-old girl with a previous clinical diagnosis of chronic active Epstein–Barr virus infection and hemophagocytic lymphohistiocytosis who was readmitted with paronychia and fever. Imaging showed an obstructing mass in the right main bronchus with atelectasis, together with widespread lymphadenopathy and hepatic lesions. An initial ultrasound-guided fine-needle biopsy of a right cervical lymph node showed EBV-associated lymphoid hyperplasia without definite lymphoma. During the subsequent admission, a newly identified left submandibular mass was sampled by ultrasound-guided core-needle biopsy. However, no finalized pathological diagnosis was available when the airway obstruction progressed. Interventional bronchoscopy was therefore undertaken under general anesthesia to obtain bronchial tissue and improve airway patency. The mass was partially removed using electrosurgical snaring and cryo-extraction, followed by argon plasma coagulation for hemostasis. Preliminary assessment of the bronchial tissue and flow cytometry supported B-cell lymphoma, and systemic treatment was initiated on 5 June 2026. Final written pathology reports for both the submandibular and bronchial specimens, issued on 10 June, supported EBV-positive DLBCL with polymorphic morphology. Chest CT on 16 June showed improved aeration of the right lung and a patent right main bronchus. At the 16-day follow-up, the patient remained on treatment without recurrent dyspnea, hypoxemia, or a need for supplemental oxygen. In this patient, interventional bronchoscopy provided additional tissue while the lymph-node specimen was under evaluation and partially restored airway patency.
Persistent infection with High-Risk Human Papillomavirus (hrHPV) causes almost all cervical cancer cases, and the world is steadily moving towards primary HPV testing for cervical cancer screening. We determined the prevalence, distribution, and trends of hrHPV genotypes at Mbarara Regional Referral Hospital (MRRH), south western Uganda. In this retrospective study, we reviewed laboratory records at MRRH for a period of six years from January 2020 and July 2025. Data on age, district of residence, HIV status, HPV test result, HPV genotype and date of testing were collected and analyzed using STATA 17. Out of the 4,852 HPV test results we retrieved, the overall prevalence of hrHPV infection was 28.52
HBV infection remains a major global health burden and a leading cause of hepatocellular carcinoma (HCC), with viral genetic variability contributing to the heterogeneity of clinical outcomes. Among HBV proteins, HBx functions as a multifunctional regulatory protein involved in viral replication, host transcriptional regulation, apoptosis, immune signaling, and oncogenic pathways. Although HBx biology has been extensively investigated, most mechanistic insights are derived from genotype B and C infections, while genotype D—particularly subgenotype D1—remains comparatively underrepresented. This narrative review provides an integrative synthesis of reported HBx mutational patterns across distinct clinical contexts of HBV infection, including acute infection, chronic hepatitis B, and HBV-related HCC, with particular emphasis on genotype D1–dominant populations from the Middle East. The review incorporates findings from previously published phase-specific studies together with relevant external literature to explore how HBx variability may relate to functional domains and disease-associated molecular patterns. Mutations are discussed in the context of major HBx functional regions, including the N-terminal regulatory region, the transactivation domain, the H-box/DDB1-binding motif, and the BH3-like region. Structural modeling, protein–protein interaction network analysis, and phylogenetic contextualization are used as conceptual and illustrative frameworks to interpret reported variants without inferring direct causality. Reported HBx variability appears to preferentially involve structurally flexible and interaction-rich regions. Recurrent substitutions, particularly involving glycine residues, are more frequently reported in acute and chronic infection settings, whereas HCC-associated variants more commonly involve C-terminal alterations and truncation events. Collectively, these observations support a hypothesis-generating framework in which HBx functional plasticity may reflect adaptive virus–host interactions under selective pressures rather than a linear oncogenic mechanism driven by individual mutations alone. Importantly, no new experimental or clinical data are presented, and all interpretations are derived from previously published studies and in silico analyses. By emphasizing genotype D1–specific evolutionary characteristics and addressing a geographical gap in HBV research, this review may provide a useful conceptual basis for future functional investigations, genotype-stratified analyses, and translational studies in HBV-associated liver disease.
Colorectal cancer (CRC) is one of the most common and life-threatening malignancies worldwide. Despite extensive research, the precise molecular mechanisms underlying CRC progression remain incompletely understood. Accumulating evidence indicates that complex interactions among oncogenic signaling pathways, non-coding RNAs, and the gut microbiota play a pivotal role in CRC pathogenesis. Among oral microbiota, Porphyromonas gingivalis (P. gingivalis) has been implicated in tumorigenesis through the induction of chronic inflammation and activation of oncogenic pathways. This study aimed to investigate the expression levels of the lncRNA CCAT2 and the c-MYC, as well as to evaluate the relative abundance of P. gingivalis and Bifidobacterium bifidum (B. bifidum) in colorectal cancer tissues compared with adjacent normal tissues. DNA and RNA were extracted from biopsy specimens obtained from 40 patients with CRC and 25 healthy controls. Complementary DNA (cDNA) was synthesized using commercial kits, and quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the expression levels of CCAT2 and c-MYC, as well as the relative abundance of the 16S rRNA genes of P. gingivalis and B. bifidum. Expression levels of lncRNA CCAT2 and c-MYC were significantly higher in CRC tissues than in normal samples (p < 0.05). Likewise, the relative abundance of P. gingivalis was significantly increased, whereas B. bifidum abundance was significantly decreased in CRC tissues (p < 0.05). In the combined study population (CRC and healthy controls), Spearman’s rank correlation analysis demonstrated significant positive correlations between P. gingivalis abundance and both CCAT2 and c-MYC expression, as well as a significant inverse correlation between B. bifidum abundance and CCAT2 expression. However, in the CRC subgroup, only the positive correlation between P. gingivalis abundance and c-MYC expression remained statistically significant. These findings demonstrate significant associations between P. gingivalis colonization, B. bifidum depletion, and oncogenic molecular alterations in CRC. Although associations involving CCAT2 were evident in the combined cohort, only the relationship between P. gingivalis abundance and c-MYC expression persisted within the CRC subgroup, suggesting that some observed correlations may primarily reflect differences between CRC patients and healthy controls. Owing to the cross-sectional design, causal inferences cannot be drawn. Further mechanistic and longitudinal studies are warranted to validate these findings and to explore the clinical utility of microbiota-based biomarkers and therapeutic strategies.
The human microbiota — comprising bacteria, fungi, archaea, and viruses — forms a complex ecosystem that maintains host homeostasis through multifaceted host-microbe interactions. Increasing evidence suggests associations between microbial dysbiosis and upper gastrointestinal malignancies, including esophageal cancer, gastric cancer, pancreatic cancer, and hepatocellular carcinoma. Mechanistically, tumor-associated microbes may contribute to carcinogenesis through several convergent pathways, including direct genotoxicity, activation of oncogenic signaling cascades such as TLR/NF-κB pathway, induction of chronic inflammation, metabolic reprogramming and modulation of anti-tumor immunity. Key tumor-associated microbiota — Fusobacterium nucleatum, Porphyromonas gingivalis, Helicobacter pylori, and hepatitis B virus— exhibit cancer-type-specific enrichment patterns and are associated with clinicopathological features and prognosis. This review synthesizes current evidence on microbiota-driven mechanisms in upper gastrointestinal cancers, critically evaluates the strength of evidence for each microbe-cancer relationship, and explores the translational potential of microbiota-based biomarkers for early detection and prognosis. However, most current evidence remains limitations, and large-scale prospective studies with standardized methodologies are needed to establish causality and enable clinical translation.
Adenovirus based vectors are commonly used as platforms for therapeutic cancer vaccines due to their high transduction efficiency, large genetic payload capacity, and intrinsic immunostimulatory properties. This systematic review evaluates the safety, immunogenicity, and clinical efficacy of adenovirus-based cancer vaccines in human clinical trials. A comprehensive literature search was conducted according to PRISMA guidelines across PubMed, Scopus, Web of Science, EMBASE, and ClinicalTrials.gov up to February 2026. Twenty clinical trials met the inclusion criteria. Adenoviral vaccines, primarily based on human Ad5 and chimpanzee-derived vectors, were used to deliver tumor-associated antigens and neoantigens. Across studies, these vaccines demonstrated a favorable safety profile, with predominantly mild-to-moderate (grade 1–2) adverse events such as injection-site reactions, flu-like symptoms, and fatigue, while severe toxicities were rare. Immunogenicity outcomes were consistent, with most trials reporting strong antigen-specific CD8⁺ and CD4⁺ T-cell responses. However, clinical efficacy remained limited when used as monotherapy, with modest objective response rates but evidence of disease stabilization and improved survival in some combination strategies. Despite encouraging immunogenicity and safety, the overall clinical benefit of adenoviral vaccines remains constrained by tumor immune evasion and pre-existing vector immunity. Future large-scale randomized trials and rational combination approaches are warranted to enhance their therapeutic potential.
Epstein-Barr virus (EBV) has been shown to play a role in the pathogenesis of several B-cell malignancies, but its role in chronic lymphocytic leukemia (CLL) remains unclear. EBV-encoded microRNAs, including BHRF1 and BART families, are thought to modulate host cell survival and apoptosis. This study aimed to evaluate the expression of EBV miRNAs in CLL patients and assess their association with disease stage and viral load. In this study, peripheral blood mononuclear cells (PBMCs) were separated using the Ficoll-Paque density gradient method from 20 EBV-positive CLL patients, including early-stage (stage 0–1, n = 10) and advanced-stage (stage 3–4, n = 10) groups. EBV viral load was quantified using real-time PCR targeting EBNA-1, and expression levels of BHRF1, BART4, and BART7 miRNAs were measured using stem-loop RT-qPCR. Correlations between miRNA expression, viral load, and clinical stage were analyzed. EBV viral load was significantly higher in advanced-stage CLL patients than in early-stage patients (P = 0.0363). However, miR-BHRF1 expression tended to be higher in early-stage patients than in advanced-stage patients; however, this difference was not statistically significant (P > 0.05). In contrast, miR-BART4 and miR-BART7 were significantly upregulated in advanced-stage patients (P < 0.05). Notably, BHRF1 expression positively correlated with EBV DNA load (r = 0.516, p = 0.019), while no significant association was observed for BART4 (p = 0.174, r = 0.316) or BART7 (p = 0.117, r = 0.361). Our results indicate that EBV-encoded miRNAs exhibit differential expression in CLL depending on disease stage and may contribute to leukemic progression. BHRF1, in particular, may serve as a biomarker of viral activity and early-stage disease, while BART miRNAs may promote advanced-stage pathogenesis. Further studies are warranted to validate these miRNAs as potential prognostic markers and therapeutic targets in CLL.
The functions of innate lymphoid cells (ILCs) remain ambiguous in cervical cancer (CC). Thus, this study sought to pinpoint prognostic genes linked to ILCs in CC through both bioinformaticis analyses and experiments. First, single-cell analysis was conducted to identify ILCs, subsequently followed by hdWGCNA to identify key module genes, and Least absolute shrinkage and selection operator (Lasso)+StepCox [both] was determined to the optimum model. Subsequently, differential expression analysis coupled with univariate Cox regression was used to discover CC survival-related genes, which were then intersected with key module genes. A prognostic model was identified using 101 combinations derived from 10 machine learning algorithms, AGPAT4, UCP2, NDUFB7, SELL, TNF, WDR45, TFRC, FCRL3, TBX21, and AKNA were identified as prognostic genes. The area under the curve (AUC) for prognostic model exceeded 0.7, and Kaplan-Meier curve demonstrated that the low-risk cohort had an extended survival duration, suggesting the prognostic model’s predictive capacity for CC survival. Additionally, reverse transcription real-time polymerase chain reaction (RT-qPCR) and Western blot were employed to verify prognostic gene expression in tissue samples. Expression study revealed that FCRL3 shown significantly increased expression in CC samples at the levels of bioinformatics, mRNA, and protein. This study identified ten ILC-related prognostic genes in CC, which offer preliminary candidate molecular markers for CC survival stratification, further large-scale clinical validation and functional research are required prior to clinical prognostic or therapeutic translation.
Cervical cancer ranks as the second most common malignancy among Nigerian women, contributing heavily to preventable mortality, particularly in low-resource settings. HPV infection is the primary cause, and vaccination provides an effective prevention strategy. However, coverage in Nigeria remains critically low. Understanding knowledge and barriers among adolescent girls is imperative for designing interventions. This study explored these determinants among in-school girls in Kwara State. This cross-sectional study surveyed 628 adolescent girls aged 9–14 years across rural, semi urban and urban LGAs in Kwara State. Multistage sampling included, random LGA selection, random school selection (7 public, 5 private per LGA), and systematic student sampling. Data were collected via comprehensive interviewer-administered questionnaires covering demographics, cervical cancer/HPV knowledge, barriers, and vaccine uptake. Analysis used STATA v18 with descriptive statistics and logistic regression with robust standard errors to identify predictors. Mean age was 12.4 years (SD:1.7); 68.0
To characterize the burden, temporal trends, geographic heterogeneity, demographic components, pandemic-era deviations, and projected age-standardized rates of bladder cancer across Africa. We conducted an ecological secondary analysis of modeled Global Burden of Disease Study 2023 estimates for the GBD aggregate labeled “African Union” and 54 African country locations from 2010 to 2023. Incidence, prevalence, deaths, and disability-adjusted life-years (DALYs) were assessed as counts and age-standardized rates (ASRs) per 100,000 population for both sexes combined. Trends were summarized using estimated annual percentage changes. Incidence trajectories were descriptively grouped using dynamic time warping, and changes in counts were partitioned into population-size, age-structure, and age-specific rate components using Das Gupta decomposition. Exploratory autoregressive integrated moving average models compared GBD-estimated rates in 2020–2023 with trajectories extrapolated from 2010 to 2019. Country-specific ASRs were projected through 2030 using log-linear models. For the GBD aggregate labeled “African Union,” incident cases increased from 16,357 in 2010 to 31,503 in 2023, prevalent cases from 73,806 to 147,599, deaths from 9,261 to 16,467, and DALYs from 232,414 to 415,746. Corresponding ASRs increased from 3.5 to 4.4 for incidence, 13.9 to 18.3 for prevalence, 2.2 to 2.6 for deaths, and 48.1 to 56.1 for DALYs. The highest estimated incidence ASRs in 2023 occurred in Tunisia, Malawi, Libya, Egypt, and Mali, while several countries with low estimated baseline rates had rapid relative increases. Population-size change was the largest decomposition component, accounting for 39.8
Endemic Burkitt Lymphoma, characterized by an MYC translocation during B-cell activation, is an aggressive, fast-proliferating cancer that predominantly accounts for more than half of all childhood cancers in sub-Saharan Africa. Although a well-established epidemiologic association exists between Epstein-Barr virus infection and Plasmodium falciparum malaria, disentangling their mechanistic interactions in the pathogenesis of endemic Burkitt Lymphoma remains difficult. To address this challenge, a comprehensive narrative review of studies published between 2010 and 2026, was conducted. Evidence from mouse models, in vitro and ex vivo studies was synthesized to identify potential key effector cells, cytokine groups, and molecular pathways likely involved in fostering an immune environment that supports lymphomagenesis. The synthesized evidence informed the development of a speculative multi-hit model of endemic Burkitt Lymphoma, in which chronic Plasmodium falciparum exposure reconfigures the immune landscape through sustained inflammation, altered effector cell function, and impaired immune surveillance. Within this framework, these changes may subsequently facilitate Epstein-Barr virus persistence, intermittent B-cell reactivation, and cumulative genomic instability, ultimately increasing the likelihood of MYC translocations and the development of endemic Burkitt Lymphoma. The review also proposes incorporating emerging immune effector populations into this conceptual multi-hit model. Although several of the mechanistic relationships explored remain inferential, the framework identifies potential therapeutic and preventive immune targets that warrant further investigation in experimental and longitudinal human studies in high-burden regions.
Despite major advances in antiretroviral therapy (ART), HIV-associated malignancies remain a significant cause of morbidity and mortality in low- and middle-income countries. In Tunisia, data on AIDS-defining cancers (ADCs) and non–AIDS-defining cancers (NADCs) among people living with HIV (PLWH) remain scarce. We conducted a descriptive retrospective cohort study over a 30-year period (1994–2024) at Farhat Hached University Hospital, Sousse, Tunisia. All PLWH who developed at least one malignant neoplasm were included. Epidemiological, clinical, immunovirological, pathological, and outcome data were retrospectively collected and analyzed. Among 655 PLWH followed during the study period, 25 patients with a median age of 36 years developed malignancies, representing 3.8
Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated malignancy characterized by a highly immune-infiltrated yet clinically heterogeneous tumor microenvironment. Iron metabolism has been proposed as a potential determinant of tumor progression and immune regulation. CD44 and transferrin receptor 1 (TfR1) represent two distinct iron uptake pathways, but their relative contribution to EBV-driven NPC and immune modulation remains unclear. Sixty-eight NPC biopsies from a Tunisian cohort were analyzed by immunohistochemistry for CD44, TfR1, EBV LMP1, PD-L1, CD8, FoxP3, and CD163. Associations with clinicopathological parameters and immune infiltrates were assessed using chi-square and Spearman correlation tests. High CD44 expression was observed in 48.5
This study examined the association between high risk human papillomavirus viral load and cervical squamous lesions using the Cobas 4800 assay and evaluated its potential as an indicator for identifying CIN2+, and analyzed the impact of multiple infections on viral load and disease risk. A total of 3,838 women who underwent hr-HPV testing were included. The Cobas 4800 assay provided cycle threshold values, which were used as indirect measures of viral load. These values were correlated with histopathological diagnoses obtained within three months of HPV testing. Among all participants, 1,660 had normal histology, 900 had CIN1, 1,019 had CIN2/3, and 259 had SCC. HPV16 Ct values decreased with increasing lesion severity in both single and multiple infections, whereas HPV18 and the 12 other hr-HPV types showed no clear correlation with lesion grade. Multiple HPV infections involving HPV16 were not associated with an increased risk of CIN2 + compared with HPV16 single infection. For both HPV16 and HPV18, Ct values did not differ significantly across CIN1, CIN2/3, and SCC between single and multiple infections. ROC curve analysis of HPV16 single infections identified a Ct threshold of 32.25 for identifying CIN2+, with an area under the curve (AUC) of 0.72, a sensitivity of 80.7
Cervical cancer is the most common cancer in women in Mozambique, where limited screening infrastructure contributes to high disease burden. While testing for high-risk human papillomavirus (hrHPV) DNA can identify women at risk for cervical cancer, its limited specificity may lead to overtreatment in screen-and-treat programs, straining resources. We performed a pilot study to evaluate preliminary feasibility of a novel, accessible test to detect hrHPV mRNA, a more specific biomarker for cervical cancer risk, from 22 women who previously screened positive for visual inspection with acetic acid at Maputo Central Hospital in Mozambique. Cervicovaginal samples were analyzed for hrHPV DNA using the Xpert HPV test. RNA was extracted from samples using a benchtop spinner instead of a centrifuge. Isothermal reverse transcription recombinase polymerase amplification (RT-RPA) assays targeting HPV 16, 18, and 45 mRNA, plus a cellular control were performed on a portable fluorimeter with results compared to the gold standard portable reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cervical biopsies were obtained and submitted for histopathologic analysis. RT-RPA and RT-qPCR results were in 100
Consistent with WHO guidance Zimbabwe is transitioning from annual single visit screen-and-treat using visual inspection with acetic acid and cervicography (VIAC) to HPV testing every three years to screen women living with HIV (WLHIV) for cervical cancer. We administered a questionnaire at three public-sector facilities in Zimbabwe to understand reasons why WLHIV accept or decline VIAC and preferences for implementation of HPV testing. A total of 451 WLHIV completed the questionnaire, of whom 414 (91.8
Abstract Background Hepatitis B virus (HBV) infection remains a major global cause of hepatocellular carcinoma (HCC), with the X protein (HBx) playing a central role in viral replication and host-virus interactions. Genetic variability within HBx, particularly in genotype D1, may influence disease progression through structural and functional alterations. Methods In this study, the HBx region from an HBV-infected patient with HCC was analyzed using high-resolution melting (HRM) and direct sequencing. The obtained sequence was compared with a genotype D1 reference, followed by in silico structural interpretation. Results Sequence analysis revealed a distinct mutational profile characterized by multiple amino acid substitutions within the transactivation domain, including H94R, S101S (synonymous), L116S, and V131T, along with a C-terminal truncation spanning amino acids 142–154 (C-terminal deletion/truncation). These alterations were located within or adjacent to functionally important regions, including domains implicated in transcriptional regulation, mitochondrial signaling, and protein-protein interactions. HRM analysis demonstrated a shift in melting temperature consistent with altered nucleotide composition. Structural interpretation suggested that the combined presence of point mutations and C-terminal truncation may contribute to localized conformational changes and altered interaction potential, although no definitive functional conclusions can be drawn. Conclusion The identified HBx variant represents a complex mutational pattern involving both non-synonymous substitutions and a C-terminal truncation, which may reflect a multi-step process of structural and functional perturbations. This observation expands the current understanding of HBx variability in genotype D1 HBV and highlights the potential relevance of combined mutational profiles in the context of HBV-associated hepatocarcinogenesis. Further studies are required to clarify the biological significance of these findings.
Epidermodysplasia verruciformis (EV) is a rare genodermatosis resulting from mutations in the EVER1/EVER2 genes, that increase vulnerability to beta-human papillomavirus (β-HPV) infection. The acquired form (AEV) develops in immunocompromised individuals, particularly organ transplant recipients, and typically manifests as pityriasis versicolor-like macules on sun-exposed areas. However, lesions confined to non-sun-exposed regions, especially the genitalia, are exceedingly uncommon and may be misdiagnosed. We report the case of a 38-year-old woman, nine years post-renal transplantation and on long-term triple immunosuppressive therapy (cyclosporine, mycophenolate mofetil, and prednisolone), who presented with progressive, non-pruritic, well-demarcated hypopigmented macules localized exclusively to her labia majora and mons pubis. The lesions were initially misdiagnosed and unsuccessfully treated as tinea versicolor. A skin biopsy revealed histopathologic features characteristic of EV, including enlarged keratinocytes with blue-gray cytoplasm and perinuclear halos and koilocytotic changes. This case emphasizes that AEV should be considered in the differential diagnosis of genital hypopigmented lesions in immunosuppressed patients. Accurate histopathologic evaluation is crucial for timely recognition, appropriate management, and ongoing surveillance to prevent missed malignant transformation.
Liquid-liquid phase separation (LLPS) dysregulation is a key driver of oncogenesis, yet its specific role in HPV-positive cervical cancer remains undefined. We hypothesized that HPV-positive tumors exploit distinct LLPS mechanisms to evade nucleolar stress surveillance, offering a novel avenue for biomarker discovery. We analyzed 70,519 single-cell transcriptomes across four histological conditions (Normal/Cancer, HPV+/-) to interrogate a curated panel of 120 LLPS-related genes. Our analytical framework integrated multi-tiered differential expression modeling with Random Forest classification to identify transformation-specific signatures. Analysis revealed a significant Cancer-HPV interaction effect characterized by the robust suppression of ribosomal proteins RPL5 and RPL11 (log₂FC ≈ − 3.4) specifically in HPV-positive cancer. Machine learning validation confirmed these genes as the top predictors (Variable Importance: RPL5 81.4
Worldwide, it is believed that high-risk human papillomavirus (hr-HPV) strains are the root cause of many types of cancers, including cervical cancer, anorectal cancers, vaginal cancers, and penile cancers, with an estimated 922, 728 females diagnosed with HPV-related cancer in 2022. Particularly, in sub-Saharan Africa, the majority of women (55.13
