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Open research questions in Viral-associated cancers and disorders

56 unresolved questions extracted from the limitations and future-work sections of 180 Viral-associated cancers and disorders papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The rarity of donor-transmitted malignancies makes it difficult to develop effective treatment strategies. The lack of definitive molecular confirmation of donor origin in cases of suspected donor-transmitted malignancies. The risk of graft rejection when using immunosuppressive therapy.

    Donor-transmitted squamous cell carcinoma in kidney transplant recipient successfully treated with checkpoint inhibitors: a case report · 2026 · DOI

  • The lack of definitive molecular confirmation of donor origin in cases of suspected donor-transmitted malignancies. The limited understanding of the effectiveness of checkpoint inhibitors in the treatment of donor-transmitted squamous cell carcinoma.

    Donor-transmitted squamous cell carcinoma in kidney transplant recipient successfully treated with checkpoint inhibitors: a case report · 2026 · DOI

  • Traditional methodologies for evaluating therapeutic efficacy in IM have significant challenges. There is a need for a new approach to assess therapeutic risk of complications in pediatric patients with infectious mononucleosis.

    The clinical utility of combining D-dimer with the C-reactive protein/albumin ratio for assessing treatment response in pediatric infectious mononucleosis · 2026 · DOI

  • Diagnostic challenges due to the rarity of the condition. Management challenges due to the patient's immunocompromised state. The need for accurate diagnosis and effective management.

    Endobronchial Epstein-Barr Virus-Associated Smooth Muscle Tumor in Advanced HIV Infection: A Rare Case · 2026 · DOI

  • EBV's host specificity presents a challenge to studying the virus in animal models. The lack of a suitable animal model for EBV infection and associated lymphoma. The need for a better understanding of the mechanisms of EBV-associated lymphoma.

    Callitrichine herpesvirus 3 in the common marmoset is a model of Epstein-Barr virus infection and associated lymphoma · 2026 · DOI

  • The molecular heterogeneity of DLBCL. The complexity of ferroptosis-related pathways. The need for further research into the molecular processes underlying disease development in EBV-positive DLBCL.

    MEF2C as a key driver in Epstein–Barr virus-positive diffuse large B-cell lymphoma · 2026 · DOI

  • Lessons This case demonstrates that EBV can trigger a fulminant, lethal triad of HLH, meningitis, and ARDS even in immunocompetent hosts, which has not been previously reported in a single patient.

    A fatal case of concurrent EBV-induced meningitis, ARDS, and HLH in an immunocompetent adult: a case report · 2026 · DOI

  • Life-threatening complications such as hemophagocytic lymphohistiocytosis (HLH), meningitis, and acute respiratory distress syndrome (ARDS) are exceptionally rare and have not been previously reported to occur concurrently in a single patient.

    A fatal case of concurrent EBV-induced meningitis, ARDS, and HLH in an immunocompetent adult: a case report · 2026 · DOI

  • study has should be acknowledged. The conclusions drawn from this review are constrained by the nature of the available evidence, which predominantly consisted of case reports and small case series. This body of literature is susceptible to publication bias, where severe or unusual presentations are more likely to be reported, and selection bias, as most reported cases originated in East Asia. The retrospective and heterogeneous design of these studies standardization of diagnostic criteria, treatments, and outcome assessments. Furthermore, the absence of large-scale prospective or controlled studies hinders the establishment of causality and robust evaluation of therapeutic strategies. Future collaborative multicenter studies are essential to generate higher-level evidence for the management of cardiovascular complications in CAEBV infection.

    Cardiovascular complications in chronic active Epstein-Barr virus infection: a narrative review · 2026 · DOI

  • Because of the retrospective design, there is inherent limitation and bias in utilising data that may be unreliable or incomplete. The clinic is situated within a tertiary referral hospital, with a potential referral bias for more severe disease. The brief follow-up period of this study makes it impossible to comment on longer-term outcomes and survival. Vital status could not be confirmed for nine patients; eight of whom were foreign nationals and one patient who was an incarcerated individual, potentially underestimating mortality. It was also not possible to comment on the cause of death. This study did not look at the effect of oncological treatment on outcomes because of ongoing research elsewhere.

    HIV-associated Kaposi sarcoma: Advanced disease and high mortality of patients referred to a multidisciplinary clinic in South Africa, 2022–2024 · 2026 · DOI

  • Further research is needed to elucidate the mechanisms of EBV-associated diseases. Studies should investigate the role of NF-kB and STAT3 signaling in EBV-associated diseases. Research should focus on developing targeted therapies for EBV-associated diseases.

    Epstein-Barr virus associated diseases: Immune alterations and targeted approaches · 2026 · DOI

  • The shared immunomodulatory strategies used by EBV to evade immune surveillance are not well understood. The mechanisms of EBV-associated diseases, including multiple sclerosis and systemic lupus erythematosus, require further study.

    Epstein-Barr virus associated diseases: Immune alterations and targeted approaches · 2026 · DOI

  • Oral cavity involvement is uncommon in DLBCL. There is a need for increased awareness of EBV-positive DLBCL with gingival involvement.

    A Rare Presentation of EBV-Positive Diffuse Large B-Cell Lymphoma with Gingival Involvement · 2026 · DOI

  • The study has a single-patient design. There is a lack of protocol biopsy to assess subclinical rejection. There is an absence of quantitative ctDNA metrics. The study has limited long-term outcomes.

    Navigating Immunotherapy in a Kidney Transplant Recipient: A Case Report of POLE-Mutated Jejunal Adenocarcinoma · 2026 · DOI

  • Further studies are needed to refine risk stratification and guide patient selection for immunotherapy in transplant recipients. Studies should investigate the use of POLE mutations as a biomarker for predicting response to immunotherapy in transplant recipients. Research should focus on optimizing dosing strategies and monitoring protocols for immunotherapy in transplant recipients.

    Navigating Immunotherapy in a Kidney Transplant Recipient: A Case Report of POLE-Mutated Jejunal Adenocarcinoma · 2026 · DOI

  • Current diagnostic approaches rely on a limited set of viral proteins and may fail to detect disease-specific antibody signatures. There is a need for a more comprehensive and sensitive approach to serological diagnostics for EBV infection.

    A novel multiplex approach for the comprehensive analysis of the Epstein-Barr virus-specific humoral immune response · 2026 · DOI

  • There is no universal therapeutic consensus for Castleman disease due to its rarity. The role of radiotherapy in the treatment of unicentric Castleman disease is not well established.

    Definitive Radiotherapy for Unresectable Unicentric Mediastinal Castleman Disease: A Case Report · 2026 · DOI

  • There are no published reports of haematopoietic stem cell transplantation (HSCT) for treatment-refractory autoimmunity in RALD. The clinical presentation of RALD resembles autoimmune lymphoproliferative syndrome (ALPS), but the two conditions are distinct.

    Case Report: Haemopoietic stem cell transplantation in refractory paediatric RAS-associated lymphoproliferative disorder · 2026 · DOI

  • In RALD, in vitro T-cell studies have shown partial resistance to inter- leukin (IL)-2 withdrawal-induced apoptosis with reduced BCL-2- Interacting Mediator of Cell Death (BIM) expression (2), whereas comparable T-cell apoptosis data have not been established as a defining feature of JMML.

    Case Report: Haemopoietic stem cell transplantation in refractory paediatric RAS-associated lymphoproliferative disorder · 2026 · DOI

  • Future research should focus on detailed characterization of additional components of the exosomal cargo to identify reliable and non-invasive biomarkers that are critical and specific for PTLD development.

    Van Latentie tot Ziekte: Epstein-Barr-Virus in Transplantatiepatiënten · 2026

  • The diagnosis of PTLD is challenging and requires careful consideration of clinical and histological features. There is a need for careful evaluation of the clinical and histological features of EBV-positive post-transplant lymphoproliferative disorder of the colon.

    Polymorphic EBV-positive post-transplant lymphoproliferative disorder of the colon mimicking EBV-positive mucocutaneous ulcer: a case report · 2026 · DOI

  • Endobronchial involvement of EBV-SMT is exceptionally uncommon. There is a need for increased awareness of this rare condition.

    Endobronchial Epstein-Barr Virus-Associated Smooth Muscle Tumor in Advanced HIV Infection: A Rare Case · 2026 · DOI

  • The study used CXR findings for PKS diagnosis, which is a pragmatic approach rather than a gold-standard imaging modality. The high-resolution CT scan (HR-CT) is not commonly used in sub-Saharan Africa due to limited affordability.

    Overall survival and associated factors among patients with pulmonary Kaposi’s sarcoma in sub-Saharan Africa · 2026 · DOI

  • There is a need for updated estimates of the prevalence of PKS among patients with cutaneous KS in sub-Saharan Africa. The current burden of PKS in sub-Saharan Africa is not well understood.

    Overall survival and associated factors among patients with pulmonary Kaposi’s sarcoma in sub-Saharan Africa · 2026 · DOI

  • The study does not compare the results to tumors treated in vehicle only mice Balb/c, as these do not engraft. The study uses a limited number of mice and tumor samples.

    HIV Infection and Opioid Treatment Enable the Engraftment of Kaposi Sarcoma‐Like Tumors Into Immunocompetent Mice · 2026 · DOI

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56 open questions have been extracted from the limitations and future-work passages of 180 Viral-associated cancers and disorders papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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