Search

DNA viruses are common in the human population and act as aetiological agents of cancer on a large scale globally. They include the human papillomaviruses (HPV), Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis viruses, and human polyomaviruses. Oncogenic viruses employ different mechanisms to induce cancer. Notably, cancer only develops in a minority of individuals who are infected, usually following protracted years of chronic infection. The human papillomaviruses (HPVs) are associated with the highest number of cancer cases, including cervical cancer and other epithelial malignancies. Hepatitis B virus (HBV) and the RNA virus hepatitis C (HCV) are significant contributors to hepatocellular cancer (HCC). Other oncoviruses include Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). The identification of these infectious agents as aetiological agents for cancer has led to reductions in cancer incidence through preventive interventions such as HBV and HPV vaccination, HPV-DNA based cervical cancer screening, antiviral treatments for chronic HBV and HCV infections, and screening of blood for transfusion for HBV and HCV. Successful efforts to identify additional oncogenic viruses in human cancer may provide further understanding of the aetiology and development of cancer, and novel approaches for prevention and treatment. Cervical cancer, caused by HPV, is the leading gynaecological malignancy in LMICs, with high age-standardised incidence and mortality rates, HCC due to HBV is an important cause of cancer deaths, and the burden of other cancer attributable to infections continues to rise globally. Hence, cancers attributable to DNA viruses have become a significant global health challenge. These viruses hence warrant continued attention and interrogation as efforts to understand them further and device further preventive interventions are critical.

ABSTRACT Kaposi sarcoma is a human herpesvirus 8–associated angio‐proliferative tumor arising from lymphatic endothelial cells. Four clinical subtypes are known: classic, epidemic, endemic, and iatrogenic. The development of Kaposi sarcoma and lymphedema may be interlinked, where each condition could potentially support the progression of the other. Post‐mastectomy lymphedema is a commonly recognized complication following radical mastectomy. Angiosarcoma is the most frequently reported neoplasm in such a situation. We present a 72‐year‐old female who developed Kaposi sarcoma on the same side of mastectomy 9 years following her initial diagnosis and treatment for cancer breast. The diagnosis of Kaposi sarcoma was based on the histopathologic findings and was confirmed with immunohistochemical staining for human herpes virus 8 and D2‐40. Lymphedema may be associated with local immune suppression manifested in the form of defective cell–mediated immunity and antigen‐presenting cell migration defect which may facilitate development of neoplasms. It is important to differentiate Kaposi sarcoma from other vascular tumors which may have a much worse prognosis. Patients with lymphedema should receive appropriate management and undergo long‐term follow‐up for early detection of any potential malignancies. [ABSTRACT FROM AUTHOR]

Background: AIDS-related Kaposi sarcoma (AIDS-KS) remains a leading cause of morbidity and mortality among people living with HIV in Africa. Mortality among people with AIDS-KS on antiretroviral therapy remains high compared with people on antiretroviral therapy who do not have AIDS-KS. Setting: People living with HIV with Kaposi sarcoma (KS) who participated in 2 randomized trials (A5263/AMC066 [advanced stage] and A5264/AMC067 [mild-to-moderate stage]) conducted by AIDS Clinical Trials Group/AIDS Malignancy Consortium in low- and middle-income countries. Methods: We estimated mortality rates over the trial period. Cox proportional hazards regressions were used to identify baseline characteristics associated with mortality and compared mortality rates between participants who had KS progression within 12 weeks of treatment initiation (early progression of KS [KS-PD]) and those who did not. Results: Of the 329 and 189 eligible participants in A5263/ AMC066 and A5264/AMC067, 71 (21.6%) and 24 (12.7%) died, respectively. In both trials, hypoalbuminemia was associated with increased hazards of death compared with normal albumin; A5263/ AMC066: mild hypoalbuminemia (adjusted hazard ratio [aHR] = 3.01; 95% CI: 1.42 to 6.29), moderate hypoalbuminemia (aHR = 5.11; 95% CI: 2.54 to 10.29), and severe hypoalbuminemia (aHR = 14.58; 95% CI: 6.32 to 35.60), and A5264/AMC067: mild hypoalbuminemia (aHR = 5.66; 95% CI: 1.90 to 16.93) and moderate hypoalbuminemia (aHR = 7.02; 95% CI: 2.57 to 19.15). The rate of death was higher among participants who had early KSPD than those without early KS-PD in A5263/AMC066 (HR = 5.09; 95% CI: 1.71 to 15.19) but not in A5264/AMC067 (HR = 1.74; 95% CI: 0.66 to 4.62). Conclusions: Albumin measurements may be used to identify individuals at higher risk of death after initiating KS treatment and for evaluation of interventions that can reduce AIDS-KS mortality. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic prompted the rapid development of vaccines, including the ChAdOx1 nCov-19 (AstraZeneca) vaccine. While effective, adverse effects have been reported, including cutaneous manifestations. Kaposi sarcoma (KS), a vascular tumor linked to Kaposi sarcoma herpesvirus/human herpesvirus 8 (HHV-8), has seen increased detection during the pandemic. This study reports a case of classic cutaneous KS in a 79-year-old male following the first dose of the ChAdOx1 nCov-19 vaccine, without prior SARS-CoV-2 infection. The patient developed multiple reddish-blue papules on his legs and feet, confirmed as KS through histopathology. Treatment included radiotherapy and sequential chemotherapy with Doxorubicin. The potential reactivation of latent HHV-8 by the vaccine is explored through mechanisms involving the SARS-CoV-2 spike protein and adenovirus vector, which may induce immune responses and inflammatory pathways. Although establishing a direct causal link remains challenging, the case highlights the need for vigilance regarding KS reactivation post-vaccination. Further large-scale studies are warranted to elucidate the relationship between COVID-19 vaccines and latent virus reactivation, ensuring comprehensive safety assessments and informed public health decisions. [ABSTRACT FROM AUTHOR]

Backgrounds: Kaposi sarcoma (KS) is a unique form of cancer with epidemiological characteristics distinct from those of other solid cancers. While common risk factors including alcohol consumption, smoking, and metabolic disorders have been well studied in various cancers, their relationship with KS remains unclear. Methods: This study used a cohort approach with adults without AIDS, utilizing data from the National Health Insurance Service in South Korea. This study examined various conventional cancer-related risk factors related to the incidence of KS, including psoriasis. Results: Alcohol consumption, smoking, body mass index, diabetes mellitus, hypertension, hypercholesterolemia, and regular exercise were not significantly associated with the incidence of KS. Additionally, older age and male sex were associated with a higher incidence of KS. KS risk was increased in pathological conditions such as psoriasis and proteinuria, which require immunosuppressive medication. Conclusions: Our study suggests that traditional cancer-related risk factors may not play a significant role in the pathogenesis of KS, unlike other cancers. This, in turn, emphasizes the importance of immunosuppression and HHV-8 infection in the development of KS. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to evaluate the efficacy of radiotherapy for skin lesions in classic Kaposi's sarcoma. A retrospective analysis was performed. Response after radiotherapy was defined as follows: Complete response indicated no clinically detectable skin lesions and no symptoms. Partial response was defined as a reduction in lesion height by more than half or a lighter lesion color compared to before treatment. In-field recurrence was defined as the appearance of new lesions within a previously irradiated field. The overall response rate was 100%. The efficacy of radiotherapy was evident, even in cases involving disseminated lesions. Further research on the optimal dose and fractionation is deemed necessary. Objectives: Classic Kaposi's sarcoma (CKS) is a rare malignancy with diverse clinical presentations, lacking a standard treatment. While localized therapies are commonly used for symptomatic lesions, radiotherapy (RT) has demonstrated effectiveness. This study aims to evaluate the efficacy of RT for treating skin lesions in CKS. Methods: A retrospective analysis was conducted on patients with KS treated between April 2012 and January 2024. In total, 69 lesions in 16 patients were included. Treatment response was defined as follows: complete response (CR) indicated the absence of clinically detectable skin lesions and symptoms; partial response (PR) was a reduction in lesion height by more than half or a lighter lesion color compared to before treatment. In-field recurrence was the appearance of new lesions within a previously irradiated field. Logistic regression analysis was used to investigate factors influencing response and in-field recurrence. Results: The median follow-up period was 52 months (range, 3–138 months). The overall response rate was 100%, with 92.8% of the patients achieving CR and 7.2% receiving PR. PR was observed in three patients with five lesions, all of which remained stable. In-field recurrence occurred in two patients with initially advanced disease, and all recurrent lesions responded to RT. No variables were significantly associated with response or in-field recurrence. Conclusions: RT for CKS showed a 100% response rate, with complete symptom relief in all cases. The effectiveness of RT was evident, even in cases involving disseminated lesions. Further research is needed to determine the optimal RT dose and fractionation. [ABSTRACT FROM AUTHOR]

BackgroundGuidelines for limited-stage human immunodeficiency virus-associated Kaposi sarcoma (AIDS/KS) recommend antiretroviral therapy (ART) as initial treatment. However, many such individuals show worsening KS and require additional chemotherapy. Methods to identify such patients are lacking.SettingWe studied whether serum levels of biomarkers associated with angiogenesis, systemic inflammation, and immune activation, which are elevated in HIV-infected individuals and implicated in the development of KS, could prospectively identify individuals with limited-stage AIDS-KS who would benefit from chemotherapy administered with ART.MethodsSerum specimens were obtained from participants in a randomized trial evaluating the value of adding oral etoposide chemotherapy to ART in treatment-naïve people with limited-stage AIDS-KS in resource-limited settings. Serum biomarkers of inflammation (C-reactive protein [CRP], interleukin [IL]-6, IL-8, IL-10, granulocyte colony stimulating factor, soluble tumor necrosis factor receptor-2), immune system activation (soluble IL-2 receptor alfa, C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10, C-C motif ligand 2/monocyte chemoattractant protein 1), and angiogenesis (vascular endothelial growth factor, matrix metalloproteinase-2, -9, endoglin, hepatocyte growth factor) were measured at entry to determine whether baseline levels are associated with KS response. On-treatment changes in biomarker levels were determined to assess how etoposide modifies the effects of ART.ResultsPretreatment CRP and IL-10 were higher in those whose KS progressed, and lowest in those who had good clinical responses. Pretreatment CRP, IL-6, and soluble tumor necrosis factor receptor-2 showed significant associations with KS progression at the week-48 primary endpoint. Immediate etoposide led to lower inflammation biomarker levels compared with ART alone. Early KS progression was associated with elevated pretreatment levels of inflammation-associated biomarkers and increasing levels post-treatment.ConclusionsQuantifying serum biomarkers, especially CRP, may help identify persons with AIDS-KS who would benefit from early introduction of chemotherapy in addition to ART.

This review analyzes the clinicopathological features, diagnostic challenges, and clinical outcomes of 60 intraoral angiosarcoma (InO-AS) and 20 intraoral Kaposi sarcoma (InO-KS) cases. These malignancies primarily affect adults, with mean ages of 52.3 years for InO-AS and 44 years for InO-KS, and are rare in children. Both show a male predilection, with InO-KS strongly linked to HIV infection. Metastatic InO-AS typically appears smaller and is located in the mandibular or maxillary gingiva. Most InO-KS cases occur in HIV-positive individuals, often in nodular form. Histological differentiation of InO-AS from poorly differentiated carcinoma and spindle cell carcinoma requires a comprehensive panel of immunohistochemical markers such as CK, CD31, and CD34, while HHV-8 antibody and CD34 help diagnose InO-KS. Treatment for InO-AS involves surgery with radiotherapy and/or chemotherapy, while InO-KS management may include antiretroviral therapy for AIDS patients. InO-AS is aggressive, with over half of patients dying from the disease, whereas InO-KS generally has a less severe course. Despite their rarity, both InO-AS and InO-KS behave similarly to their extraoral counterparts. A key limitation noted in this review is the inconsistent histopathological reporting of AS, particularly regarding histopathological grade, which complicates the assessment and comparison of treatment outcomes.

Background Reemergence of human herpesvirus 8 (HHV-8)–induced Kaposi sarcoma (KS) in people living with HIV (PLWH) despite antiretroviral therapy (ART) poses a clinical challenge because they already have favorable CD4 T-cell numbers and undetectable viral loads. We observed that clinical presentation in PLWH on ART resembled classic KS found in older HIV-uninfected patients and hypothesized that immunosenescence may thus play a role in occurrence of KS on ART. We compared viral and immune factors implicated in the development of KS in ART-treated PLWH (HIV KS) and HIV-uninfected classic KS patients (cKS), compared to controls without KS (HIV Control, cControls respectively). Methods Plasma, peripheral blood mononuclear cell, and skin tissues were obtained from 11 HIV KS and 11 cKS patients and 2 groups of age-matched controls. Results HIV KS participants were younger than cKS (aged 53 vs 75 years). HHV-8 genotypes did not differ between groups. Despite the younger age and a lower CD4/CD8 ratio, activated, exhausted, and senescent T-cell frequencies were similar between HIV KS and cKS. Anti–HHV-8 immunoglobulin G levels were higher and circulating HHV-8 DNA lower in HIV KS compared with cKS. Circulating platelet-derived growth factors AA-BB and granulocyte colony-stimulating factors were higher in HIV KS We observed similar levels of HHV-8 DNA and PD-1 expression in skin lesions from HIV KS and cKS patients. Conclusions Altogether, early immune senescence could be involved in the development of KS in ART-treated PLWH. Higher anti–HHV-8 immunoglobulin G levels could be linked with lower circulating viral load. Such insights should help developing therapeutical strategies to prevent development and treat KS in PLWH on ART. [ABSTRACT FROM AUTHOR]

Background: Kaposi sarcoma (KS) is a multicentric vascular and lymphatic neoplasm caused by human herpesvirus 8 (HHV‐8). It generally concerns the elderly and immunosuppressed population. Four major clinical types of KS have been described. The most common subtype is Classical KS (CKS). Objectives: Our retrospective study aimed to better define prognostic subgroups among patients with CKS, which is the most common in our country. Method: Between 2014 and 2020, 43 patients with CKS were treated with local excision, radiotherapy and chemotherapy. Reviewed information included demographics, clinical features, laboratory findings, treatment responses and overall survival. Results: During the follow‐up, eight patients (18.6%) died of CKS. The complete response rate was 46.5%, partial response and stable disease 51.2%, and progressive disease 2.3% of all patients. Gender, haemoglobin level at diagnosis, and disseminated involvement were prognostic factors affecting survival in all patients. Conclusion: We confirmed that male gender, low haemoglobin levels, and disseminated involvement are associated with poor prognosis in CKS patients. It is the only Turkish study in which prognostic analysis was performed for this rare cancer. [ABSTRACT FROM AUTHOR]

Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma‐associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV‐1 TAT protein can be essential in developing AIDS‐associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV‐specific TAT profile among PLHIV who developed KS. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Human herpes virus 8 (HHV‐8) or Kaposi sarcoma herpesvirus (KSHV) is an opportunistic oncovirus that causes multiple pathologic entities.We present a case of fatal HHV‐8‐associated multisystem illness with disseminated Kaposi sarcoma and HHV8‐associated lymphoproliferative disorder with systemic inflammation. We conducted a narrative review of the literature on HHV‐8 in transplantation with a goal of illuminating the spectrum of HHV‐8‐associated diseases in this vulnerable population, modes of disease transmission, and the potential role for donor and recipient screening.HHV‐8‐associated KS, primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and KSHV inflammatory cytokine disorder (KICS) may affect transplant recipients; with the exception of KS, these conditions are rare but carry high morbidity and mortality.HHV‐8‐associated diseases have diverse and protean manifestations in transplant recipients, with potentially fatal outcomes. HHV‐8 seroprevalence among organ donors and the magnitude of risk for donor‐derived HHV‐8 infection or clinically significant disease remain unknown and require further study. [ABSTRACT FROM AUTHOR]

Simple Summary: While sun exposure and associated tissue changes stemming from ultraviolet radiation are closely associated with the most common forms of skin cancer, far less is known regarding rare types of skin cancer. In this study, for the first time, we used a light microscopy technique to evaluate connective tissue changes in samples from patients with six different types of rare skin cancers, assessing the relationship between these changes, patient age, and whether tumors arose on sun-exposed parts of the body. We found that these tissue changes were most pronounced for patients with specific cancers known to be linked to chronic sun damage and tumors arising on sun-exposed parts of the body. We also noted tumor type-specific trends in terms of sex ratios, sites of tumor presentation, and the relationship between the development of particular tumors and patient immunosuppression. Our results are important and novel as they expand the available data associated with these rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic, and/or therapeutic approaches. (1) Background: Rare skin cancers include epithelial, neuroendocrine, and hematopoietic neoplasias as well as cutaneous sarcomas. Ultraviolet (UV) radiation and sunburns are important drivers for the incidence of certain cutaneous sarcomas; however, the pathogenetic role of UV light is less clear in rare skin cancers compared to keratinocyte cancer and melanoma. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure among selected rare skin cancers (atypical fibroxanthoma [AFX], pleomorphic dermal sarcoma [PDS], dermatofibrosarcoma protuberans [DFSP], Kaposi sarcoma [KS], Merkel cell carcinoma [MCC], and leiomyosarcoma [LMS]) while taking into account relevant clinical variables (age, sex, and body site). (2) Methods: We newly established a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 210 rare skin cancers from 210 patients with their clinical variables. (3) Results: TEG values were correlated with age and whether tumors arose on UV-exposed body sites. TEG values were significantly higher in AFX and PDS cases compared to all other analyzed rare skin cancer types. As expected, TEG values were low in DFSP and KS, while MCC cases exhibited intermediate TEG values. (4) Conclusions: High cumulative UV exposure is more strongly associated with AFX/PDS and MCC than with other rare skin cancers. These important results expand the available data associated with rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic and/or therapeutic approaches. [ABSTRACT FROM AUTHOR]

Abstract is missing (Quiz)

Lele Yu, Binhai Zhang, Hu Wan Department II of Infectious Diseases, Hangzhou Xixi Hospital, Hangzhou Sixth People’s Hospital, Hangzhou, Zhejiang, 310023, People’s Republic of ChinaCorrespondence: Hu Wan, Email yll8024@126.comIntroduction: Kaposi sarcoma (KS) incidence has decreased since the initiation of combination antiretroviral therapy (cART), but it remains the most common cancer in people with HIV/AIDS (PWHA). PWHA with advanced immunosuppression who initiate antiretroviral therapy are susceptible to the occurrence of an immune reconstitution inflammatory syndrome (IRIS).Case Presentation: This report covers the case of a 25-year-old male with AIDS-related KS who relapsed after Liposomal Doxorubicin, but recovered well after administration of nab-paclitaxel (Nab-PTX).Conclusion: This is a rare case in choosing Nab-PTX to treat relapsed AIDS-KS and get good feedback. We report the case to provide a possible solution to treat AIDS-KS.Keywords: Kaposi sarcoma, nab-paclitaxel, HIV, case report

Background Kaposi Sarcoma (KS) has been historically associated with HIV, especially in people with advanced immunosuppression. Its prevalence decreased over time, but management remains difficult especially when the diagnosis is late and there is a visceral involvement. Bone localization, and particularly the vertebral one, is rare. We herein present a case of vertebral localizations of KS and performed a review literature to assess demographic, clinical characteristics and treatment outcomes in people with HIV. Methods The systematic review was carried out by following the PRISMA guidelines and registering the protocol in PROSPERO database (n. registration: CRD42024548626). We included all cases of vertebral localizations of KS from January 1rst 1981 to December 31rst, 2023. Results Twenty-two cases, including ours, were ever reported in people with HIV, mostly males (95.4%), with a median age of 35 years (IQR: 32-44), median CD4+ T cell count of 80 cell/mm3 (IQR 13-111), 31.8% with high HIV viral load. Five people received HIV and KS diagnosis simultaneously. In all cases, but one, there were multiple sites involved. Most spine lesions were localized at thoracic and lumbar levels (59.1%), causing pathological fractures in 2 cases. Chemotherapy and radiotherapy were performed in 50% and 18.2% cases, respectively. 22.7% persons died, stability and improvement/disease regression were reported for 13.6% and 22.7% persons, respectively, while 9.9% had a significant disease progression and a person was lost to follow-up. Conclusions Despite progresses in treatment, late presentation of KS, especially with spine involvement may have a poor prognosis. More efforts are needed to promote access to HIV testing, especially when indicating conditions are present.

DNA viruses are common in the human population and act as aetiological agents of cancer on a large scale globally. They include the human papillomaviruses (HPV), Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis viruses, and human polyomaviruses. Oncogenic viruses employ different mechanisms to induce cancer. Notably, cancer only develops in a minority of individuals who are infected, usually following protracted years of chronic infection. The human papillomaviruses (HPVs) are associated with the highest number of cancer cases, including cervical cancer and other epithelial malignancies. Hepatitis B virus (HBV) and the RNA virus hepatitis C (HCV) are significant contributors to hepatocellular cancer (HCC). Other oncoviruses include Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). The identification of these infectious agents as aetiological agents for cancer has led to reductions in cancer incidence through preventive interventions such as HBV and HPV vaccination, HPV-DNA based cervical cancer screening, antiviral treatments for chronic HBV and HCV infections, and screening of blood for transfusion for HBV and HCV. Successful efforts to identify additional oncogenic viruses in human cancer may provide further understanding of the aetiology and development of cancer, and novel approaches for prevention and treatment. Cervical cancer, caused by HPV, is the leading gynaecological malignancy in LMICs, with high age-standardised incidence and mortality rates, HCC due to HBV is an important cause of cancer deaths, and the burden of other cancer attributable to infections continues to rise globally. Hence, cancers attributable to DNA viruses have become a significant global health challenge. These viruses hence warrant continued attention and interrogation as efforts to understand them further and device further preventive interventions are critical.

BackgroundIFNL4 genetic variants that are strongly associated with clearance of hepatitis C virus have been linked to risk of certain opportunistic infections (OIs) and cancers, including Kaposi sarcoma, cytomegalovirus infection, and herpes simplex virus infection. As the interferon (IFN) λ family plays a role in response to viral, bacterial, and fungal infections, IFNL4 genotype might affect risk for a wide range of OIs/cancers.MethodsWe examined associations between genotype for the functional IFNL4 rs368234815 polymorphism and incidence of 16 OIs/cancers among 2310 men with human immunodeficiency virus (2038 white; 272 black) enrolled in the Multicenter AIDS Cohort Study during 1984-1990. Our primary analyses used Cox proportional hazards models adjusted for self-reported racial ancestry to estimate hazard ratios with 95% confidence intervals, comparing participants with the genotypes that generate IFN-λ4 and those with the genotype that abrogates IFN-λ4. We censored follow-up at the introduction of highly effective antiretroviral therapies.ResultsWe found no statistically significant association between IFNL4 genotype and the incidence of Kaposi sarcoma (hazard ratio, 0.92 [95% confidence interval, .76-1.11]), cytomegalovirus infection (0.94 [.71-1.24]), herpes simplex virus infection (1.37 [.68-2.93]), or any other OI/cancer. We observed consistent results using additive genetic models and after controlling for CD4 cell count through time-dependent adjustment or restriction to participants with a low CD4 cell count.ConclusionsThe absence of associations between IFNL4 genotype and these OIs/cancers provides evidence that this gene does not affect the risk of disease from opportunistic pathogens.

Acquired immunodeficiency syndrome (AIDS)-associated Kaposi sarcoma (KS) is an angioproliferative neoplasia caused by infection with human herpesvirus 8 (HHV-8). It typically presents with mucocutaneous involvement, but it can be disseminated. Initial presentation with primarily pulmonary KS is rare. We present a case of a 32-year-old male with untreated human immunodeficiency virus (HIV) diagnosed 1 year before presentation who developed progressively worsening cough and shortness of breath for 6 months. He was hospitalized twice and treated for unresolved pneumonia in an outside hospital. The patient concomitantly developed purplish nodules on his face, then the upper trunk, back, chest, and thighs bilaterally that gradually increased in size and number. Histopathology findings from skin lesions were consistent for KS. Bronchoscopy found multiple erythematous plaques throughout the tracheobronchial tree with telangiectasias and inflammation suggestive of pulmonary KS. His imaging findings and positive serum HHV-8 polymerase chain reaction (PCR) were consistent with disseminated KS. He started antiretroviral therapy (ART) to treat his HIV infection, followed by liposomal doxorubicin chemotherapy. But both ART and chemotherapy were interrupted due to adherence and insurance issues. The patient was readmitted with acute respiratory failure requiring mechanical ventilation with multiple vasopressors that led to the patients demise. The late recognition of KS diagnosis and delayed treatment can lead to worse outcomes.

Epstein-Barr virus (EBV; human herpesvirus 4; HHV-4) and Kaposi sarcoma-associated herpesvirus (KSHV; human herpesvirus 8; HHV-8) are human gammaherpesviruses that have oncogenic properties. EBV is a lymphocryptovirus, whereas HHV-8/KSHV is a rhadinovirus. As lymphotropic viruses, EBV and KSHV are associated with several lymphoproliferative diseases or plasmacytic/plasmablastic neoplasms. Interestingly, these viruses can also infect epithelial cells causing carcinomas and, in the case of KSHV, endothelial cells, causing sarcoma. EBV is associated with Burkitt lymphoma, classic Hodgkin lymphoma, nasopharyngeal carcinoma, plasmablastic lymphoma, lymphomatoid granulomatosis, leiomyosarcoma, and subsets of diffuse large B-cell lymphoma, post-transplant lymphoproliferative disorder, and gastric carcinoma. KSHV is implicated in Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease, and KSHV-positive diffuse large B-cell lymphoma. Pathogenesis by these two herpesviruses is intrinsically linked to viral proteins expressed during the lytic and latent lifecycles. This comprehensive review intends to provide an overview of the EBV and KSHV viral cycles, viral proteins that contribute to oncogenesis, and the current understanding of the pathogenesis and clinicopathology of their related neoplastic entities.

BackgroundKaposi sarcoma is one of the most prevalent HIV-associated malignancies in sub-Saharan Africa and is often diagnosed at advanced stage of disease. Only 50% of KS patients who qualify for chemotherapy receive it and adherence is sub-optimal.Methods57 patients > 18 years with newly diagnosed KS within the AMPATH clinic network in Western Kenya were purposively selected to participate in semi-structured interviews stratified by whether they had completed, partially completed, or not completed chemotherapy for advanced stage KS. We based the interview guide and coding framework on the situated Information, Motivation, Behavioral Skills (sIMB) framework, in which the core patient centered IMB constructs are situated into the socioecological context of receiving care.ResultsOf the 57 participants, the median age was 37 (IQR 32-41) and the majority were male (68%). Notable barriers to chemotherapy initiation and adherence included lack of financial means, difficulty with convenience of appointments such as distance to facility, appointment times, long lines, limited appointments, intrapersonal barriers such as fear or hopelessness, and lack of proper or sufficient information about chemotherapy. Factors that facilitated chemotherapy initiation and adherence included health literacy, motivation to treat symptoms, improvement on chemotherapy, prioritization of self-care, resilience while experiencing side effects, ability to carry out behavioral skills, obtaining national health insurance, and free chemotherapy.ConclusionOur findings about the barriers and facilitators to chemotherapy initiation and adherence for KS in Western Kenya support further work that promotes public health campaigns with reliable cancer and chemotherapy information, improves education about the chemotherapy process and side effects, increases oncology service ability, supports enrollment in national health insurance, and increases incorporation of chronic disease care into existing HIV treatment networks.

Kaposi sarcoma (KS) continues to cause substantial morbidity and mortality in populations at risk in the southern United States. Utilizing biospecimens from the Houston site of the Young Men's Affiliate Project, 351 men who have sex with men had blood tested for KS-associated herpesvirus (KSHV) IgG. Seroprevalence, seroconversion between time points, and demographic and clinical correlates were measured. KSHV prevalence was 36.7% and incidence was 8.9 per 100 person-years. Furthermore, prevalence and incidence were higher among Black individuals, people living with HIV, and those with a history of syphilis. Further research on KSHV risk may improve health disparities in KS diagnosis and outcomes. [ABSTRACT FROM AUTHOR]

Kaposi sarcoma (KS) arises in the context of 4 epidemiologic-clinical settings: Classic, endemic, epidemic, and iatrogenic; the most serious types are endemic and epidemic, and visceral involvement occurs mostly in the latter. Several morphological variants of KS have been described, of which the anaplastic one is highly aggressive. We report the case of an anaplastic KS arising from the ascending colon in a 32-year-old human immunodeficiency virus (HIV)-positive male patient with a 6-year history of multiple mucocutaneous KS. Anaplastic KS is most frequent in endemic and classic settings; there are ten cases of anaplastic KS reported in HIV-positive male patients. There is now strong evidence that KS is a clonal neoplasm characterized by chromosomal instability at the molecular level. According to the morphological spectrum and contemporary hypotheses of oncogenesis, conventional KS should be considered an incipient endothelial neoplasia, multiple or single, and anaplastic KS, the fully developed stage of the malignant neoplasm. [ABSTRACT FROM AUTHOR]

Kaposi sarcoma (KS) is a vascular proliferative tumor caused by human herpesvirus 8. At present, the treatment of KS is difficult and refractory. Here, we report a 68‐year‐old man who was diagnosed with a classical KS with tinea pedis and onychomycosis, infected by Trichophyton rubrum, and treated with itraconazole and thalidomide after locational excision of several bigger nodules. The lesions were relieved during treatment, and recurred after discontinuation. Retreatment still achieved good effect and the therapy was tapered down after control. After the whole course of treatment, the skin lesions subsided significantly without obvious adverse reactions, which showed that itraconazole combined with thalidomide may be another effective and safe treatment for KS in some cases. [ABSTRACT FROM AUTHOR]

Background Males have 2–3-fold greater risk of cancer than females at most shared anatomic sites, possibly reflecting enhanced immune surveillance against cancer in females. We examined whether these sex differences remained among immunocompromised adults. Methods Using the Transplant Cancer Match (TCM) study, we estimated the male-to-female incidence rate ratio in TCM (M:F IRRTransplant) for 15 cancer sites diagnosed between 1995 and 2017 using Poisson regression. Male to female IRRs in the general population (M:F IRRGP) were calculated using expected cancer counts from the Surveillance, Epidemiology, and End Results Program, standardized to the transplant population on age, race and ethnicity, and diagnosis year. Male to female IRRs were compared using a chi-square test. Results Among 343 802 solid organ transplants, 211 206 (61.4%) were among men and 132 596 (38.6%) among women. An excess cancer incidence in males was seen in transplant recipients, but the sex difference was attenuated for cancers of the lip (M:F IRRTransplant: 1.81 vs M:F IRRGP: 3.96; P  <  .0001), stomach (1.51 vs 2.09; P  =  .002), colorectum (0.98 vs 1.43; P  <  .0001), liver (2.39 vs 3.44; P  =  .002), kidney (1.67 vs 2.24; P  <  .0001), bladder (2.02 vs 4.19; P  <  .0001), Kaposi sarcoma (1.79 vs 3.26; P  =  .0009), and non-Hodgkin lymphoma (1.34 vs 1.64; P  <  .0001). The M:F IRRTransplant was not statistically different from the M:F IRRGP for other cancer sites. Conclusions Although male solid organ transplant recipients have higher cancer incidence than female recipients, the attenuation in the male to female ratio for many cancers studied relative to the general population might suggest the importance of immunosurveillance, with some loss of advantage in female recipients due to immunosuppression after transplantation. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of disseminated Kaposi sarcoma (KS) in a kidney transplant recipient without primary cutaneous involvement. The patient, a 69-year-old male, had a history of end-stage renal disease and had undergone a kidney transplant. The KS was complicated by KSHV-inflammatory cytokine syndrome (KICS), which presented as multi-system inflammation. The patient's case was atypical because it occurred in the United States without known geographic or sexual risk factors. The article provides information on the prevalence, diagnosis, and treatment of KS in transplant recipients. [Extracted from the article]

Sub-Saharan Africa bears the largest public health burden of Kaposi sarcoma (KS), a leading cause of cancer mortality. Quality of life (QOL) assessments in cancer patients can provide information on prognosis beyond traditional biomarkers or biological measures. The prognostic value of QOL measures in patients with HIV-KS was evaluated. Prognostic associations of baseline QOL scores (by quartiles or thresholds for clinical importance) and changes in QOL scores (using minimum important difference) over the first 3 months of therapy were evaluated in 112 participants with HIV-KS randomised to receive ART, with or without chemotherapy. Cox’s regression analysis assessed the prognostic contribution of QOL scores from the EORTC QLQ-C30 questionnaire. Survival curves were generated using the Kaplan–Meier method. Baseline QOL scores did not predict overall survival. The change in the 3-month QOL scores for the global health scale, fatigue, and pain domains was prognostic; the hazard ratios were 3.88 (95% CI 1.32–11.38, p = 0.01), 3.72 (95% CI 1.61–8.62, p = 0.00) and 5.96 (95% CI 2.46–14.43, p = 0.00), respectively. QOL assessments can provide useful prognostic information in patients with HIV-KS. Patients lacking meaningful improvement early into treatment represent a population at high risk of death.

The COVID-19 pandemic prompted the rapid development of vaccines, including the ChAdOx1 nCov-19 (AstraZeneca) vaccine. While effective, adverse effects have been reported, including cutaneous manifestations. Kaposi sarcoma (KS), a vascular tumor linked to Kaposi sarcoma herpesvirus/human herpesvirus 8 (HHV-8), has seen increased detection during the pandemic. This study reports a case of classic cutaneous KS in a 79-year-old male following the first dose of the ChAdOx1 nCov-19 vaccine, without prior SARS-CoV-2 infection. The patient developed multiple reddish-blue papules on his legs and feet, confirmed as KS through histopathology. Treatment included radiotherapy and sequential chemotherapy with Doxorubicin. The potential reactivation of latent HHV-8 by the vaccine is explored through mechanisms involving the SARS-CoV-2 spike protein and adenovirus vector, which may induce immune responses and inflammatory pathways. Although establishing a direct causal link remains challenging, the case highlights the need for vigilance regarding KS reactivation post-vaccination. Further large-scale studies are warranted to elucidate the relationship between COVID-19 vaccines and latent virus reactivation, ensuring comprehensive safety assessments and informed public health decisions.

Simple Summary: Following infection with HIV, individuals are immunocompromised. Their weakened immune system puts them at a higher risk of certain cancers like Kaposi sarcoma and lymphoma. Even with antiretroviral therapy for HIV infection, these cancers remain common in developing countries, while in developed countries, there is a decline in some cancers but an increase in deaths from others. This review explores why these cancers happen in people with HIV and finds that the current treatment is not enough to prevent them. Understanding these reasons is crucial to improving the diagnosis and treatment of both HIV and its associated cancers, highlighting the need for more research to tackle this ongoing health issue. The immune deficiency associated with human immunodeficiency virus (HIV) infection causes a distinct increased risk of developing certain cancer types. Kaposi sarcoma (KS), invasive cervical cancer and non-Hodgkin's lymphoma (NHL) are the prominent malignancies that manifest as a result of opportunistic viral infections in patients with advanced HIV infection. Despite the implementation of antiretroviral therapy (ART), the prevalence of these acquired immunodeficiency syndrome (AIDS)-defining malignancies (ADMs) remains high in developing countries. In contrast, developed countries have experienced a steady decline in the occurrence of these cancer types. However, there has been an increased mortality rate attributed to non-ADMs. Here, we provide a review of the molecular mechanisms that are responsible for the development of ADMs and non-ADMs which occur in HIV-infected individuals. It is evident that ART alone is not sufficient to fully mitigate the potential for ADMs and non-ADMs in HIV-infected individuals. To enhance the diagnosis and treatment of both HIV and malignancies, a thorough comprehension of the mechanisms driving the development of such cancers is imperative. [ABSTRACT FROM AUTHOR]

Kaposi sarcoma (KS), caused by Herpesvirus‐8 (HHV‐8; KSHV), shows sporadic, endemic, and epidemic forms. While familial clustering of KS was previously recorded, the molecular basis of hereditary predilection to KS remains largely unknown. We demonstrate through genetic studies that a dominantly inherited missense mutation in BPTF segregates with a phenotype of classical KS in multiple immunocompetent individuals in two families. Using an rKSHV.219‐infected CRISPR/cas9‐model, we show that BPTFI2012T mutant cells exhibit higher latent‐to‐lytic ratio, decreased virion production, increased LANA staining, and latent phenotype in viral transcriptomics. RNA‐sequencing demonstrated that KSHV infection dysregulated oncogenic‐like response and P53 pathways, MAPK cascade, and blood vessel development pathways, consistent with KS. BPTFI2012T also enriched pathways of viral genome regulation and replication, immune response, and chemotaxis, including downregulation of IFI16, SHFL HLAs, TGFB1, and HSPA5, all previously associated with KSHV infection and tumorigenesis. Many of the differentially expressed genes are regulated by Rel‐NF‐κB, which regulates immune processes, cell survival, and proliferation and is pivotal to oncogenesis. We thus demonstrate BPTF mutation‐mediated monogenic hereditary predilection of KSHV virus‐induced oncogenesis, and suggest BPTF as a drug target. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted at a dermatology center to determine the relationship between the cutaneous CD4:CD8 ratio in skin biopsies and the serum CD4:CD8 ratio in patients with Kaposi sarcoma (KS) and HIV infection. The study found that an inverted cutaneous CD4:CD8 ratio correlated with an inversion in the serum CD4:CD8 ratio. The researchers also observed that a perivascular-peritumoral pattern of CD8+ TL distribution was the most frequent in KS patients. The study suggests that the role of CD8+ TL in KS is poorly understood and further research is needed to understand its implications. [Extracted from the article]

Dermatologic complications are common following allogeneic hematopoietic stem cell transplantation, but dermatologic complications among pediatric patients undergoing hematopoietic stem cell transplantation for the treatment of sickle cell disease have been poorly characterized. In this case series of 17 patients (<21 years old) with sickle cell disease who underwent hematopoietic stem cell transplantation, 16 (94.1%) experienced one or more dermatologic complications after transplant, with the most common complications including acute or chronic mucocutaneous graft‐versus‐host disease (GVHD) (34.1% of complications), skin eruptions of unknown origin (15.9% of complications), infections (15.9% of complications), and chemotherapy‐related pigmentary changes (11.4% of complications). Patients who developed acute or chronic skin GVHD were significantly older at the time of hematopoietic stem cell transplantation. These findings highlight the need to closely monitor for dermatologic complications in pediatric patients who undergo hematopoietic stem cell transplantation for sickle cell disease and underscore the importance of involving dermatology early on when skin complications occur, although further research with a larger multicenter study could help clarify the risk for dermatologic complications and help identify potential ways to mitigate this risk. [ABSTRACT FROM AUTHOR]

The advent of deep learning techniques has ignited interest in medical image processing. The proposed work in this paper suggests one of the edge technologies in deep learning, which is recommended, based on a Radiomics feature extraction model for the effective detection of Kaposi sarcoma, a vascular skin lesion expression that indicates the most prevalent cancer in AIDS patients. This work investigates the role and impact of medical image fusion on deep feature learning based on ensemble learning in the medical domain. The model is crafted wherein the pre-built ResNet50 (Residual network) and Visual Geometry Group (VGG16) are fine-tuned and an ensemble learning approach is applied. The pre-defined CNN was incrementally regulated to determine the appropriate standards for classification efficiency improvements. Our findings show that layer-by-layer fine-tuning can improve the performance of middle and deep layers. This work would serve the purpose of masking and classification of skin lesion images, primarily sarcoma using an ensemble approach. Our proposed assisted framework could be deployed in assisting radiologists by classifying Kaposi sarcoma as well as other related skin lesion diseases, based on the positive classification findings. [ABSTRACT FROM AUTHOR]

We report the case of a HIV-seronegative 57 year-old man, with known classic Kaposi's disease and in whom a secondary localization in the upper left limb led to carpal and metacarpal lysis in the left hand. This unfavorable local evolution led to left transhumeral amputation. [ABSTRACT FROM AUTHOR]

ABSTRACT We present an interesting case of a 62-year-old black female, presented to the ophthalmological hospital with a little "nevus" on the left eye previously visualized at the mirror, with one month of development. Physical examination with slit lamp (biomicroscopy) showed a group of painless veins, with vascular redness, and a mass nodular aspect in the mid temporal bulbar conjunctiva, of approximately 2mmx4mm.

Kaposi's sarcoma should be considered in the differential diagnosis in young patients with penile lesions and no risk factors. A 37-year-old heterosexual man with no other medical history applied presented with a non-itchy and painless penile lesion, for three months. The HIV 1-2 serology was negative via ELISA test. Histopathological analysis of the lesion revealed a tumor composed of atypical spindle cells, below a partially ulcerated surface. There was also an abundance of plasma cells admixed within the neoplastic cells. The patient was diagnosed as HIV-negative, HHV-8 positive Kaposi sarcoma. Although penile Kaposi sarcoma is extremely rare, classical Kaposi sarcoma should be considered in the differential diagnosis of penile lesions. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma caused by Kaposi's sarcoma-associated virus, is a rare malignancy in the general population with unique features. However, clinical presentation on the feet can mimic a diabetic foot ulcer. Here we describe the case of a 63-year-old male with type 2 diabetes, who presented with a lesion on the left 4th toe. Left foot radiograph in lateral and dorsoplantar views were normal. Full skin examination identified lesions with a similar morphology on the forearms. A HIV antigen/antibody test was negative, histology showed CD31 positive spindle cells and the presence of Kaposi's sarcoma-associated virus confirming the diagnosis of Kaposi's sarcoma. Kaposi's sarcoma-associated virus' lytic cycle can be triggered by the immunosuppressive state caused by tissue's chronic exposure to a hyperglycaemic environment. A thorough general examination to identify lesions elsewhere in the body can help to identify the systemic nature of the disease. Pedal lesions in patients with diabetes with an atypical presentation that are refractory to standard treatment should prompt early histological examination. Early diagnosis and intervention can improve the chances of remission. [ABSTRACT FROM AUTHOR]

(1) Background: Rare skin cancers include epithelial, neuroendocrine, and hematopoietic neoplasias as well as cutaneous sarcomas. Ultraviolet (UV) radiation and sunburns are important drivers for the incidence of certain cutaneous sarcomas; however, the pathogenetic role of UV light is less clear in rare skin cancers compared to keratinocyte cancer and melanoma. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure among selected rare skin cancers (atypical fibroxanthoma [AFX], pleomorphic dermal sarcoma [PDS], dermatofibrosarcoma protuberans [DFSP], Kaposi sarcoma [KS], Merkel cell carcinoma [MCC], and leiomyosarcoma [LMS]) while taking into account relevant clinical variables (age, sex, and body site). (2) Methods: We newly established a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 210 rare skin cancers from 210 patients with their clinical variables. (3) Results: TEG values were correlated with age and whether tumors arose on UV-exposed body sites. TEG values were significantly higher in AFX and PDS cases compared to all other analyzed rare skin cancer types. As expected, TEG values were low in DFSP and KS, while MCC cases exhibited intermediate TEG values. (4) Conclusions: High cumulative UV exposure is more strongly associated with AFX/PDS and MCC than with other rare skin cancers. These important results expand the available data associated with rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic and/or therapeutic approaches.

Kaposi sarcoma (KS) is an AIDS-defining angio-proliferative malignancy, with the Kaposi sarcoma-associated herpes virus (KSHV) as its etiologic agent. Upon treatment with chemotherapy, a proportion of HIV-associated KS patients experience disease recurrence within a few months of completing treatment. We aimed at determining whether KSHV-specific adaptive immune responses were associated with KS recurrence upon complete remission. We conducted a prospective cohort study. The primary outcome was the recurrence of HIV-associated KS. An immunofluorescence assay was used to determine anti-KSHV antibodies, an enzyme-linked immunospot was conducted for T cell responses, PCR was carried out to determine KSHV status, and flow cytometry was used for CD4 counting and immunophenotyping. KSHV detection in PBMCs was high and not associated with KS recurrence-free survival (p = 0.29). Anti-KSHV antibody titers were high and not associated with recurrence-free survival (p = 0.63). KSHV-specific T cell responses dropped from baseline levels among individuals with recurrence, but the drop was not statistically significant. Individuals experiencing KS recurrence had a significantly higher proportion of T cell subsets expressing PD1, while those with sustained remission had a significant increase in CD4 T cell counts from baseline levels during the follow-up period (p = 0.02). Anti-KSHV antibodies are not a good correlate of protection from KS recurrence. T cells in individuals experiencing KS recurrence hadhigh PD1 expression, while an increase in CD4 counts was associated with sustained KS remission.