Oncogenic Viral Infections Research Articles

The Oncogenic Role of VWA8-AS1, a Long Non-Coding RNA, in Epstein-Barr Virus-Associated Oral Squamous Cell Carcinoma: An Integrative Transcriptome and Functional Analysis.

Dysregulated long non-coding RNA (lncRNA) expression is linked to various cancers and may be influenced by oncogenic Epstein-Barr virus (EBV) infection, a known and detectable risk factor in oral squamous cell carcinoma (OSCC) patients. However, research on the oncogenic role of EBV-induced lncRNAs in OSCC is limited. To identify lncRNA-associated EBV infection and OSCC carcinogenesis, the differential expression of RNA-seq datasets from paired normal adjacent and OSCC tissues, and microarray data from EBV-negative and EBV-positive SCC25 cells, were identified and selected, respectively, for interaction, functional analysis, and CCK-8 cell proliferation, wound healing, and invasion Transwell assays. In OSCC tissues, 6731 differentially expressed lncRNAs were identified when compared to normal tissues from RNA-seq datasets, with 295 linked to EBV-induced OSCC carcinogenesis from microarray datasets. The EBV-induced lncRNA VWA8-AS1 showed significant upregulation in EBV-positive SCC25 cells and EBV-infected adjacent and OSCC tissue samples. VWA8-AS1 potentially promotes OSCC via the lncRNA-miRNA-mRNA axis or direct protein interactions, affecting various cellular processes. Studies in OSCC cell lines revealed that elevated VWA8-AS1 levels enhanced cell migration and invasion. This study demonstrates VWA8-AS1's contribution to tumor progression and possible interactions with its targets in OSCC, offering insights for future research on functional mechanisms and therapeutic targets in EBV-associated OSCC.

Transitional Cell Carcinoma Arising From the Renal Allograft: A Case Series and Review of the Literature.

Transitional cell carcinoma (TCC) of the urinary tract appears more commonly amongthe transplant population. The increased incidence of TCC has been primarily associated with the male gender, BK virus (BKV), and smoking.We report a case series and comprehensive review of the literature. The comprehensive literature review was conducted via Pubmed using the keywords "transitional cell carcinoma" and "renal allograft."At our institution, all of our cases presented with hematuria, and hydronephrosis was present in 50% (two) of our cases. BKV was detected in 75% (three) of our cases. The average time from BKV detection to TCC diagnosis was 5.6 years. The average time from transplant to TCC diagnosis was 11.25 years. Upon review of the literature, a total of 20 cases were reported of TCC arising within the renal allograft. Of those patients, 55% (11) presented with hematuria, 30% (six) had BKV, and 35% (seven) were found to have hydronephrosis. The average time from BKV detection to TCC diagnosis was 3.4 years and the average time from transplant to TCC diagnosis was 9.5 years. Given the relatively increased incidence of neoplasm among solid organ transplant recipients, painless hematuria in a renal transplant recipient should raise concern for malignancy, especially in those with prior oncogenic viral infections, history of smoking, other environmental exposures, or in those with high cumulative doses of immunosuppressive medications.

Monocyte and Macrophage Functions in Oncogenic Viral Infections.

Monocytes and macrophages are part of innate immunity and constitute the first line of defense against pathogens. Bone marrow-derived monocytes circulate in the bloodstream for one to three days and then typically migrate into tissues, where they differentiate into macrophages. Circulatory monocytes represent 5% of the nucleated cells in normal adult blood. Following differentiation, macrophages are distributed into various tissues and organs to take residence and maintain body homeostasis. Emerging evidence has highlighted the critical role of monocytes/macrophages in oncogenic viral infections, mainly their crucial functions in viral persistence and disease progression. These findings open opportunities to target innate immunity in the context of oncogenic viruses and to explore their potential as immunotherapies.

Roles of Human Endogenous Retrovirus-K-Encoded Np9 in Human Diseases: A Small Protein with Big Functions.

Human Endogenous Retrovirus Sequences (HERVs) constitute up to 8% of the human genome, yet not all HERVs remain silent passengers within our genomes. Some HERVs, especially HERV type K (HERV-K), have been found to be frequently transactivated in a variety of inflammatory diseases and human cancers. Np9, a small protein translated from the HERV-K env reading frame, has been reported as an oncogenic protein and is present in a variety of tumors and transformed cells. The Np9 protein can crosstalk with many cellular factors and is involved in the pathogenicity of various diseases, including some oncogenic virus infections. In the current review, we summarize recent findings about Np9 clinical relevance/implications, its mediated cellular functions/mechanisms, and potential targeted therapies in development.

Paraneoplastic Syndrome After Kidney Transplantation: Frequency, Risk Factors, Differences to Paraneoplastic Occurrence of Glomerulonephritis in the Native Kidney, and Implications on Long-Term Kidney Graft Function.

Posttransplant malignancies are an important complication of solid organ transplantation. Kidney transplant recipients are at particularly high risk of cancer development. The most relevant risk factors of carcinogenesis are the use of immunosuppressive agents and oncogenic viral infections. Additionally, immune dysregulation caused by these factors may predispose to various types of organ damage. Paraneoplastic glomerular diseases are one of the most interesting and understudied cancer manifestations. The appropriate diagnosis of paraneoplastic glomerular damage can be challenging in kidney transplant recipients, due to factors inherent to concomitant medication and common comorbidities. Recent advances in the field of molecular and clinical nephrology led to a significant improvement in our understanding of glomerular diseases and their more targeted treatment. On the other hand, introduction of novel anticancer drugs tremendously increased patients' survival, at the cost of kidney-related side effects. Our review aims to provide insights into diagnosis and treatment of paraneoplastic glomerular diseases, with a special attention to kidney transplant recipients.

Oncogenic viral antigens for engineered T cell immunotherapy: Challenges and opportunities

AbstractViruses that cause malignancies such as hepatocellular carcinoma and cervical cancer are the cause of approximately 20% of all human cancers. In recent years, engineered T cell immunotherapy targeting tumor‐associated antigens (TAAs) has had some success against virus‐associated cancer, although these treatments are associated with side effects. TAA‐specific‐modified T cells may kill cancer cells but they also react with and damage healthy tissue. During an oncogenic virus infection, viral DNA integrates into the host genome, leading to the expression of viral‐specific antigens in the tumor in a restricted and durable manner. The cross‐reactive side‐effects of conventional TAA‐specific engineered T cell treatment can be avoided by creating engineered T cells that target oncogenic viral antigens. To chart a course for the discovery of additional viral‐specific antigens and their combination with immune checkpoint inhibition therapies, this review summarizes the development, preclinical research, and clinical application of oncogenic viral antigen–specific T cell immunotherapy. This review also addresses challenges such as virus mutation and diverse integration, which can result in the loss of the target.

Molecular and Immunopathological Investigations of Marek’s Disease in HVT Vaccinated Chicken Flocks

Background: The present investigation was carried out on poultry carcasses brought to the Department of Veterinary Pathology, LUVAS, Hisar from Herpesvirus of turkeys (HVT) vaccinated chicken flocks and suspected for viral neoplastic conditions on the basis of necropsy. Conventional and molecular techniques for the confirmation of the Marek’s disease (MD) were studied. For differential diagnosis from other oncogenic viral infections immunohistochemistry as an important tool was investigated. Methods: The conventional diagnosis of MD) was done on basis of clinical signs, gross lesions and histopathology of proliferate lesions; as lymphomatous lesions consist of pleomorphic lymphocytes. For confirmatory diagnosis molecular techniques were employed to detect MD virus specific Meq gene by Taqman probe real time PCR and nested PCR. For differential diagnosis of mixed oncogenic viral infections, immunohistochemistry (IHC) using B and T cell differentiation markers (CD79 alpha and CD3) was employed. Result: Specific Meq gene by Taqman probe real time PCR was positive in 92.5% suspected cases; while nested PCR technique gave positivity in 55% cases. The immunohistochemical reactivity for CD3 gave positive reactivity in the cytoplasm and cell membrane and negative reaction for CD79 alpha in MD positive cases, while in cases with mixed infections of MDV and other viral neoplastic conditions, cells showed positive reactivity to both CD3 and CD79 alpha in neoplastic proliferates.

Rewiring of the Host Cell Metabolome and Lipidome during Lytic Gammaherpesvirus Infection Is Essential for Infectious-Virus Production.

Oncogenic virus infections are estimated to cause ~15% of all cancers. Two prevalent human oncogenic viruses are members of the gammaherpesvirus family: Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV). We use murine herpesvirus 68 (MHV-68), which shares significant homology with KSHV and EBV, as a model system to study gammaherpesvirus lytic replication. Viruses implement distinct metabolic programs to support their life cycle, such as increasing the supply of lipids, amino acids, and nucleotide materials necessary to replicate. Our data define the global changes in the host cell metabolome and lipidome during gammaherpesvirus lytic replication. Our metabolomics analysis found that MHV-68 lytic infection induces glycolysis, glutaminolysis, lipid metabolism, and nucleotide metabolism. We additionally observed an increase in glutamine consumption and glutamine dehydrogenase protein expression. While both glucose and glutamine starvation of host cells decreased viral titers, glutamine starvation led to a greater loss in virion production. Our lipidomics analysis revealed a peak in triacylglycerides early during infection and an increase in free fatty acids and diacylglyceride later in the viral life cycle. Furthermore, we observed an increase in the protein expression of multiple lipogenic enzymes during infection. Interestingly, pharmacological inhibitors of glycolysis or lipogenesis resulted in decreased infectious virus production. Taken together, these results illustrate the global alterations in host cell metabolism during lytic gammaherpesvirus infection, establish essential pathways for viral production, and recommend targeted mechanisms to block viral spread and treat viral induced tumors. IMPORTANCE Viruses are intracellular parasites which lack their own metabolism, so they must hijack host cell metabolic machinery in order to increase the production of energy, proteins, fats, and genetic material necessary to replicate. Using murine herpesvirus 68 (MHV-68) as a model system to understand how similar human gammaherpesviruses cause cancer, we profiled the metabolic changes that occur during lytic MHV-68 infection and replication. We found that MHV-68 infection of host cells increases glucose, glutamine, lipid, and nucleotide metabolic pathways. We also showed inhibition or starvation of glucose, glutamine, or lipid metabolic pathways results in an inhibition of virus production. Ultimately, targeting changes in host cell metabolism due to viral infection can be used to treat gammaherpesvirus-induced cancers and infections in humans.

Second primary cancers in people with HIV/AIDS: a national data linkage study of incidence and risk factors.

The evidence regarding the characteristics of second primary cancer (SPC) in people living with HIV (PLWHIV) is limited. We performed a national population-based data linkage study to determine the incidence and risk factors for SPC in PLWHIV in Australia between 1982 and 2012. We conducted a probabilistic data linkage study to compare the incidence of SPC over time, defined using HIV treatment eras, for SPCs related to oncogenic viral infection in comparison with non-infection related SPCs. Risk factors considered included age at diagnosis of cancer, sex, HIV exposure modality and CD4+ count. Of 29,383 individuals diagnosed with HIV, 3,123 who developed a first primary cancer were included in the analysis. Among them, 229 cases of SPC were identified across 27,398 person years of follow-up. The most common SPCs were non-Hodgkin lymphomas (n=71, 31%). The incidence of SPC overall did not change over time, however there was an increase in individuals diagnosed with HIV in later eras (p-trend=0.001). The incidence of non-infection related SPC increased over time and was associated with older age (p-trend=0.005) and the acquisition of HIV in later eras (p-trend <0.001). Conversely, the incidence of infection-related SPC decreased (p-trend <0.001), but this was no longer significant after adjustment for age (p-trend=0.14). The risk of SPC in PLWHIV in Australia remains high, with a temporal increase observed in non-infection related cancer, likely due to ageing of the population. Optimal screening and prevention strategies for SPC in PLWHIV are increasingly important.

Психологический стресс и папилломавирусная инфекция. Взаимосвязь и пути решения

Stress is a non-specific response of the body to stimuli that disrupt homeostasis. Stress can suppress the immune function and therefore increase the risk of immunodeficiency disorders, including human papillomavirus (HPV) infection. Stress-induced immunosuppression is especially important for infection-related cancer since damage to cellular immunity can stimulate the development of oncogenic viral infection. A connection was established between psychosocial stress and the development of SILs (squamous intraepithelial lesions) in women (formerly known as ‘cervical intraepithelial neoplasia (CIN)’ in the International Classification of Diseases (ICD-10)). This connection ends with immune response, which, in turn, depends on the duration of exposure to stressors: a shorter duration of stress shifts specific immunity to innate immunity, and chronic stress shifts it from a Th1-type response to a Th2-type response. Against the background of cognitive behavioral therapy, the incidence of severe SILs/CIN is significantly lower than in the absence of psychological treatment. However, the use of adaptive ways of coping with stress does not exclude the need for pathogenetic (antiviral) therapy for HPV infection. One of the most demanded medications in the pharmaceutical market of Russia is inosine pranobex. It is included in the register of antiviral medications used for HPV treatment. It enhances antiviral protection against HPV, slows or stops oncogenesis in the cervix, which together contribute to a rapid virus elimination. Key words: stress, immunosuppression, human papillomavirus infection, SILs/CIN, inosine pranobex

Photodynamic Therapy: A Prospective Therapeutic Approach for Viral Infections and Induced Neoplasia.

The recent COVID-19 pandemic outbreak and arising complications during treatments have highlighted and demonstrated again the evolving ability of microorganisms, especially viral resistance to treatment as they develop into new and strong strains. The search for novel and effective treatments to counter the effects of ever-changing viruses is undergoing. Although it is an approved procedure for treating cancer, photodynamic therapy (PDT) was first used against bacteria and has now shown potential against viruses and certain induced diseases. PDT is a multi-stage process and uses photosensitizing molecules (PSs) that accumulate in diseased tissues and eradicates them after being light-activated in the presence of oxygen. In this review, studies describing viruses and their roles in disrupting cell regulation mechanisms and signaling pathways and facilitating tumorigenesis were described. With the development of innovative “or smart” PSs through the use of nanoparticles and two-photon excitation, among other strategies, PDT can boost immune responses, inactivate viral infections, and eradicate neoplastic cells. Visualization and monitoring of biological processes can be achieved in real-time with nanomedicines and better tissue penetration strategies. After photodynamic inactivation of viruses, signaling pathways seem to be restored but the underlying mechanisms are still to be elucidated. Light-mediated treatments are suitable to manage both oncogenic viral infections and induced neoplasia.

Oncogenic viruses, cancer biology, and innate immunity.

Malignancies that arise as a result of viral infection account for roughly 15% of cancer cases worldwide. The innate immune system is the body's first line of defense against oncogenic viral infection and is also involved in the response against viral-driven tumors. In this review, we discuss research advances made over the last five years elucidating how the innate immune system recognizes and responds to oncogenic viruses, how these viruses have evolved to escape this immune pressure, and ways that innate immunity can inform the development of novel therapeutics against oncogenic viral infection and their associated cancers.

S1389 The Impact of Race on the Overall Survival Rate of Hepatocellular Carcinoma in the African-American Population

Introduction: Hepatocellular carcinoma (HCC) accounts for approximately 90% of the incidence of all primary liver cancers. It is also the fifth most prevalent malignancy worldwide and the fourth global leading cause of death. Previous U.S.-based studies on survival rates suggest ethnic disparities among HCC patients; however, this is incompletely understood due to a variety of risk factors. Notable risk factors include oncogenic viral infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), alcohol abuse, and metabolic syndrome secondary to obesity and diabetes mellitus. This study aims to investigate whether race plays a role in the overall survival rate of hepatocellular carcinoma. Methods: Using the cBioPortal platform and systematic bioinformatical-analysis of The Cancer Genome Atlas (TCGA) PanCancer Atlas dataset, we analyzed the effect of race on overall survival rate. The study included 360 HCC patients (234 living patients and 126 deceased patients). The following races were included: White, Black or African American, and Asian. Results: The impact of race on the overall survival rate of hepatocellular carcinoma was statistically significant (p < 0.0206) and appeared to be higher in the African American group (64.71%) compared to the White (57.92%). Of note, the Asian group had the highest overall survival rate (73.13%). (Figure) Conclusion: The findings in this study suggest that race may play a role in the risk of developing hepatocellular carcinoma and potential treatment options. Further studies are warranted to evaluate the genetic alterations in various race groups.Figure 1.: Hepatocellular carcinoma overall survival among the African American, White, and Asian populations.

Malignancies in adult kidney transplant candidates and recipients: current status.

Posttransplant malignancies, particularly recurrent and de novo, in solid organs including kidney transplant recipients (KTRs) are a significant complication associated with substantial mortality, largely attributed to the long-term immunosuppression necessary to maintain allograft tolerance. Older age at transplantation and oncogenic virus infection along with pretransplant malignancies are among the main factors contributing to the risk of cancer in this population. As the mean age of transplant candidates rises, the rate of transplant recipients with pretransplant malignancies also increases. The eligibility criteria for transplantation in patients with prior cancer have recently changed. The overall risk of posttransplant malignancies is at least double after transplantation, including KTRs, relative to the general population, and is most pronounced for skin cancers associated with UV radiation and virally mediated tumors. The risk of renal cell carcinoma is specifically increased in the kidney transplant population. The therapy for cancer in transplant patients is associated with risk of higher toxicity, and graft rejection and/or impairment, which poses a unique challenge in its management. Reduction of immunosuppression and the use of mammalian target of rapamycin inhibitors are common after cancer diagnosis, although optimal immunosuppression for transplant recipients with cancer remains undefined. Suboptimal cancer treatment contributing to a worse prognosis has been reported for malignancies in this population. In this article, we focus on the prevalence and outcomes of posttransplant malignancies, cancer therapy including a short overview of immunotherapy, cancer screening and prevention strategies, and immunosuppression as a cancer risk factor. The 2020/2021 recommendations of the Kidney Disease: Improving Global Outcomes and the American Society of Transplantation for transplant candidates with a history of cancer are presented.

Time-resolved transcriptomes reveal diverse B cell fate trajectories in the early response to Epstein-Barr virus infection.

Epstein-Barr virus infection of B lymphocytes elicits diverse host responses via well-adapted transcriptional control dynamics. Consequently, this host-pathogen interaction provides a powerful system to explore fundamental processes leading to consensus fate decisions. Here, we use single-cell transcriptomics to construct a genome-wide multistate model of B cell fates upon EBV infection. Additional single-cell data from human tonsils reveal correspondence of model states to analogous invivo phenotypes within secondary lymphoid tissue, including an EBV+ analog of multipotent activated precursors that can yield early memory B cells. These resources yield exquisitely detailed perspectives of the transforming cellular landscape during an oncogenic viral infection that simulates antigen-induced B cell activation and differentiation. Thus, they support investigations of state-specific EBV-host dynamics, effector B cell fates, and lymphomagenesis. To demonstrate this potential, we identify EBV infection dynamics in FCRL4+/TBX21+ atypical memory B cells that are pathogenically associated with numerous immune disorders.

Aspects of Antiviral Strategies Based on Different Phototherapy Approaches: Hit by the Light.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which caused the COVID-19 pandemic spreading around the world from late 2019, served as a ruthless reminder of the threat viruses pose to global public health. The synthesis of new antiviral drugs, as well as repurposing existing products, is a long-term ongoing process which has challenged the scientific community. One solution could be an effective, accessible, and rapidly available antiviral treatment based on phototherapy (PT). PT has been used to treat several diseases, and relies on the absorption of light by endogenous molecules or exogenous photosensitizers (PS). PT has often been used in cancer treatment and prophylaxis, and as a complement to established chemotherapy and immunotherapy in combined therapeutic strategy. Besides significant applications in anticancer treatment, studies have demonstrated the beneficial impact of PT on respiratory, systemic, emerging, and oncogenic viral infections. The aim of this review was to highlight the potential of PT to combat viral infections by summarizing current progress in photodynamic, photothermal, and photoacoustic approaches. Attention is drawn to the virucidal effect of PT on systemic viruses such as the human immunodeficiency virus and human herpes viruses, including the causative agent of Kaposi sarcoma, human herpes virus (HHV8). PT has good potential for disinfection in anti-norovirus research and against pandemic viruses like SARS-CoV-2.

Abstract 643: Non-classical sources of tumour specific antigen in checkpoint inhibitor response

Abstract A large-scale meta-analysis of over 1000 CPI (immune checkpoint blockade) treated patients across multiple cancer types broadly categorised biomarkers into four categories: sources of antigen leading to T-cell responses, host-derived factors, immune evasion and infiltration mechanisms. Our analyses established tumour mutation burden (TMB) as the strongest predictor of CPI response, alongside clonal TMB and CXCL9 expression. However, over half of the patients in our cohort who responded to CPI treatment did not have high-TMB and showed no evidence of oncogenic viral infections, hence suggesting alternative sources of antigen could be driving the immune response. As well as this, data from the CPI1000 cohort suggested that the biomarkers identified in an extensive systematic review only accounted for ~60% of the variance in CPI response, promoting the search for non-classical sources of antigen. Extending the cohort to encompass 2500+ patients, using available genomic and transcriptomic data from checkpoint inhibitor trials and industry partners, the previously published multivariate predictor will be further validated in a larger patient cohort inclusive of more cancer types. The CPI1000 cohort utilised primarily whole exome-sequencing therefore, had limited ability to discern non-coding sources of tumour antigen and cell-type specific predictors of response. The CPI2500+ cohort will incorporate several additional cohorts as well as single-cell and T-cell reactivity data. The raw data will be harmonised across studies and processed using a robust bioinformatics pipeline. As well as this, alternative (non-classical) sources of tumour specific antigen will be studied. Alternative sources of antigen can originate from a diverse range of biological processes including retained introns, stop codon loss mutations and cancer associated bacterial/viral epitopes. Data from this exploratory analysis will be coupled with peptide reactivity assays from local UCL patient TIL (tumour infiltrating lymphocyte) and PMBC (peripheral blood mononuclear cells) samples to validate immunogenicity. Current analysis has identified a novel subgroup of CPI-responders with low-TMB who have significantly higher rates of microbial diversity, consistent with a diverse tumour microbiome providing a source of immunogenic antigens in the absence of high-TMB. Here we will present insights from CPI2500+ and highlight the importance of emerging non-classical sources of tumour specific antigen. Citation Format: Krupa Thakkar, Danwen Qian, Hongui Cha, Thomas B. Watkins, Charles Swanton, Kevin Litchfield. Non-classical sources of tumour specific antigen in checkpoint inhibitor response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 643.

Incidence and mortality of post-transplant lymphoproliferative disorders after kidney transplantation: A real-world retrospective analysis in Japan.

Post-transplant lymphoproliferative disorder is a potentially life-threatening complication that has a greater risk of occurrence in the setting of immunosuppression and oncogenic viral infections after transplant surgery. Few studies have reported the cumulative incidence, histological subtypes and clinical outcomes of this disorder in kidney transplant recipients. We retrospectively investigated 34 post-transplant lymphoproliferative disorder patients diagnosed out of the 1210 kidney transplant recipients who had undergone the surgery at the two largest centers in Japan between January 1983 and December 2017. A total of 32 patients (94.1%) developed late-onset post-transplant lymphoproliferative disorder (diagnosed 1year after transplantation). The cumulative incidence rates were 0.76% and 1.59% at 5 and 10years post-transplantation, respectively. The central nervous system was the most common site (35.3%, 12/34). Overall survival was similar between patients with and without central nervous system lesions (P=0.676). Of all of the cases, 23.5% (8/34) were detected through cancer screening. Importantly, patients with screening-detected post-transplant lymphoproliferative disorder had better overall survival than those with the disorder who had been symptom detected (P=0.0215). Overall survival was significantly reduced in patients who developed the disorder compared with those who did not (P=0.0001). Post-transplant lymphoproliferative disorder was more likely to occur in the late post-transplantation period, which showed that long-term medical examination for transplant recipients is required. Based on our findings, we propose vigilant, long-term, cancer screening in kidney transplant recipients.

Malignant neoplasms associated with HIV infection. Problems and solutions (problem outline)

HIV infection refers to socially significant diseases. As a result of the wide coverage of effective antiretroviral therapy for people living with HIV, the rates of AIDS-related mortality have significantly decreased. At the same time, there was a noticeable increase in morbidity and mortality from other non-AIDS-related diseases, not the last place in this list is occupied by malignant neoplasms. A decrease in the frequency of AIDS-associated tumors and an increase in the proportion of AIDS-unassociated tumors are significant changes in the structure of malignant neoplasms. There is a complex relationship between HIV-induced immune suppression, chronic antigenic stimulation and concomitant oncogenic viral infections, which increases the risk of developing malignant tumors in these patients. People living with HIV have higher rates of cancer mortality associated with both the lack of adequate antitumor therapy, complications of treatment, and the existence of a direct relationship between immunosuppression and tumor progression. This article analyzes the problems that arise in the treatment of oncological HIV-infected patients, and offers specific practical steps to solve complex interdisciplinary problems.

Epstein-Barr Virus Predicts Malignancy After Pediatric Heart Transplant, Induction Therapy and Tacrolimus Don’t

BackgroundPatients after heart transplantation are at increased risk for malignancy secondary to immunosuppression and oncogenic viral infections. Most common among children is posttransplant lymphoproliferative disorder (PTLD), occurring in 5% to 10% of patients. We used a national database to examine the incidence and risk factors for posttransplant malignancy. MethodsThe United Network for Organ Sharing database was queried for pediatric (<18 years) heart transplant recipients from October 1987 through November 2019. Freedom from malignancy after transplant was assessed with Kaplan-Meier analysis. Cox regression was performed to generate hazard ratios (HRs) and 95% CIs for risk of malignancy development. ResultsOf 8581 pediatric heart transplant recipients, malignancy developed in 8.1% over median follow-up time of 6.3 years, with PTLD compromising 86.4% of the diagnosed cancers. The incidence of PTLD development was 1.3% at 1 year and 4.5% at 5 years. Older age at the time of transplant was protective against the development of malignancy (HR, 0.98; 95% CI, 0.96-0.99; P < .001), whereas a history of previous malignancy (HR, 1.9; 95% CI, 1.2-3.0; P = .007) and Ebstein-Barr virus (EBV) recipient-donor mismatch (HR, 1.7; 95% CI, 1.3-2.2; P < .001) increased the risk. Induction therapy, used in 78.9% of the cohort, did not increase malignancy risk (P = .355) nor did use of maintenance tacrolimus (P = .912). ConclusionsPTLD occurred after 7% of pediatric heart transplants, with risk increased by younger age and EBV mismatch, highlighting the importance of PTLD monitoring in EBV-seronegative recipients. Induction therapy, used in most of the pediatric heart transplants, does not seem to increase posttransplant malignancy nor does tacrolimus, the most commonly used calcineurin inhibitor.