Human Immunodeficiency Virus Malignancies Research Articles

Impact of Antiretroviral Therapy on the Risk of Recurrence in HIV-1 Infected Patients with Kaposi Sarcoma: A Multicenter Cohort Experience.

Kaposi sarcoma (KS) remains a relevant malignancy in human immunodeficiency virus (HIV)-infected patients with a non-standardized management; despite past suggestions that ritonavir-boosted protease inhibitor (bPI)-based regimens could be preferable, no combination antiretroviral therapy (cART) regimen was demonstrated to outperform the others and the impact of new drugs, drug classes or paradigms was never investigated nor proven better than previous therapeutic regimes. In order to do this, we retrospectively collected data regarding HIV-infected patients with a diagnosis of KS last seen in six Italian centers after 1 January 2013. A total of 104 KS cases in 99 patients was analyzed for 945.34 patient-year follow-up (PYFU). Twenty-six patients had visceral localizations. Thirty-three patients were treated with chemotherapy, four with electrochemotherapy, and 12 with α-interferon (α-IFN). At censor, 22% received a bPI-based, 14% a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based, and 28% an integrase inhibitor (INI)-based standard cART, 24% a less drug regimen and 12% a mega-cART. Twelve recurrence episodes were observed in seven patients for an incidence of 1.27 per 100 PYFU. Two patients with no evidence of recurrence episodes died for other reasons. In our experience, KS recurrence episodes were infrequent. Despite the increasing use of new antiretroviral drug classes and new treatment paradigms, no excess of recurrence episodes was observed in patients receiving such cART regimens.

EBV-dUTPase Modulates Host Immune Responses Potentially Altering the Tumor Microenvironment in EBV-associated Malignancies

While the use of long-term antiretroviral therapy (ART) has improved immune function and reduced the incidence of some malignancies in human immunodeficiency virus (HIV-1) infected patients, this is not the case for non-Hodgkin’s lymphoma, an AIDS-defining cancer, and Hodgkin lymphoma, a non-AIDS defining cancer. Epstein-Barr virus (EBV) is an independent factor that adversely affects risk and/or survival among patients with Diffuse Large B cell Lymphoma (DLBCL) or classical Hodgkin lymphoma in immunocompetent patients as well as in HIV-1 infected individuals on ART. While cells infected with EBV in EBV-associated malignancies generally express one type of the latency programs, a small number of cells in these tumors are expressing EBV genes associated with lytic replication of the virus, which suggests that products from lytic or abortive-lytic replication may contribute to lymphomagenesis. However, the potential roles of these proteins in lymphomagenesis remain unclear. In this study we demonstrate that the EBV deoxyuridine triphosphate nucleotidohydrolase (dUTPase), an early protein produced during abortive/lytic EBV replication, is expressed in nasopharyngeal carcinoma (NPC) tumors in a mouse model of NPC, an EBV associated malignancy. Furthermore, screening of sera from 4 cohorts of patients diagnosed with AIDS, DLBCL, NPC and breast cancer (BC) by ELISA revealed an increase in IgG antibodies to the EBV-dUTPase in a subset of patients with AIDS, DLBCL and NPC relative to the controls. Finally, using an in vitro model of EBV infection we demonstrate that the EBV-dUTPase also inhibits T-cell function thus, allowing the proliferation of EBV immortalized B-cells. Altogether, our data support the premise that the EBV-dUTPase can modulate host immune responses and potentially alter the tumor microenvironment by promoting the survival/proliferation of immortalized B-cells, which may lead to lymphomagenesis. Key Words: Epstein-Barr virus, dUTPase, lymphomagenesis

Malignancies in human immunodeficiency virus infected patients in India: Initial experience in the HAART era

Background & objectives:Limited data are available on malignancies in human immunodeficiency virus (HIV)-infected patients from India. We undertook this study to assess the frequency and spectrum of malignancies in HIV-infected adult patients during the first eight years of highly active antiretroviral therapy (HAART) rollout under the National ART Programme at a tertiary care centre in New Delhi, India.Methods:Retrospective analysis of records of patients registered at the ART clinic between May 2005 and December 2013 was done.Results:The study included 2598 HIV-infected adult patients with 8315 person-years of follow up. Malignancies were diagnosed in 26 patients with a rate of 3.1 (IQR 2.1-4.5) cases per 1000 person-years. The median age for those diagnosed with malignancy was 45 (IQR 36-54) yr, which was significantly (P<0.01) higher compared with those not developing malignancies 35 (IQR 30-40) yr. The median baseline CD4+ T-cell count in patients with malignancy was 135 (IQR 68-269) cells/µl compared to 164 (IQR 86-243) cells/µl in those without malignancies. AIDS-defining cancers (ADCs) were seen in 19 (73%) patients, while non-AIDS-defining cancers (NADCs) were observed in seven (27%) patients. Malignancies diagnosed included non-Hodgkin's lymphoma (16), carcinoma cervix (3), Hodgkin's lymphoma (2), carcinoma lung (2), hepatocellular carcinoma (1), and urinary bladder carcinoma (1). One patient had primary central nervous system lymphoma. There was no case of Kaposi's sarcoma.Interpretation & conclusions:Malignancies in HIV-infected adult patients were infrequent in patients attending the clinic. Majority of the patients presented with advanced immunosuppression and the ADCs, NHL in particular, were the commonest malignancies.

Spectrum of malignancies in human immunodeficiency virus – positive patients at a Tertiary Care Centre in South India

India has a very large number of patients living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Opportunistic infections in these patients are commonly encountered. However, malignancies in such patients also do occur. The aim was to study the spectrum of malignancies in HIV-positive patients at a tertiary health care center. Retrospective study. The cases were retrieved from pathology record files at our Institute from January 2003 to December 2008. The follow-up was obtained from Medical oncology records. The morphology of each case was reviewed along with immunohistochemistry wherever done. There were 61 such cases (51 males, 10 females). The age range was 7-78 years with a median of 35 years. The clinical presentation varied according to the malignancy. The largest group was non-Hodgkin lymphoma (18 nodal, 23 extra-nodal). The others included carcinoma breast (4), chronic myeloid leukemia (3), Burkitt Leukemia (2), squamous cell carcinoma anal region (2), multiple myeloma (2) and one each of miscellaneous malignancies (7). Malignancies in HIV positive individual occurred in younger individuals. Non-Hodgkin lymphomas, especially extra-nodal lymphomas, were the most common malignancy. There were no cases of proven Kaposi's sarcoma or invasive cervical carcinomas. There were two cases of multiple myeloma which are infrequently reported.

Metastatic Merkel cell carcinoma of the oral cavity in a human immunodeficiency virus–positive patient and the detection of Merkel cell polyomavirus

The etiology of Merkel cell carcinoma (MCC) was recently linked to a newly identified human virus, the Merkel cell polyomavirus (MCPyV). The discovery that MCPyV plays an important role in the tumorigenesis of >80% of MCCs provides an explanation for the increased incidence of this rare malignancy in human immunodeficiency virus (HIV)-positive and immunocompromised patients. We report an unusual metastasis of MCC to the mandibular gingiva of an HIV-positive patient. In addition to routine hematoxylin-eosin and immunohistochemical studies, we also performed a molecular biologic analysis to look for the presence of MCPyV in this case. We detected evidence of the MCPyV genome in this lesion similar to what has been observed for MCCs reported in other immunocompromised patients. These results stress the importance of combining morphologic and molecular biologic analyses in the evaluation of MCC, because confirmation of viral etiology would likely affect the choice of treatment and prognosis when specific antiviral therapy becomes available for this aggressive tumor.

Strong impact of highly active antiretroviral therapy on survival in patients with human immunodeficiency virus-associated Hodgkin's disease.

Hodgkin's disease (HD) is the most common non-acquired immunodeficiency syndrome (AIDS)-defining malignancy in human immunodeficiency virus (HIV)-infected patients. We analysed the outcome of patients with HIV-associated HD (HIV-HD) with respect to the use and efficacy of highly active antiretroviral therapy (HAART) and other prognostic factors. To evaluate the effects of several variables on overall survival (OS), Kaplan-Meier statistics and extended Cox regression analysis were performed. Response to HAART was used as a time-dependent variable and was defined as an increase of >0.1 x 10(9) CD4 cells/l and/or at least one viral load <500 copies/ml during the first 2 years following diagnosis of HIV-HD. Fifty-seven patients with HIV-HD diagnosed between 1990 and 2002 were included in the study. In the Cox model, the only factors independently associated with OS were HAART response [relative hazard (RH) 0.19; 95% confidence interval (CI) 0.06-0.60], complete remission (RH 0.30, 95% CI 0.13-0.72), and age <or=45 years (RH 0.23; 95% CI 0.09-0.60). Median survival time in patients without HAART response was 18.6 months, whereas the median survival time in patients with HAART response was not reached (89% OS at 24 months). In this cohort, a significant improvement in survival was found in patients with HIV-HD who responded to HAART.

High prevalence of high risk human papillomavirus-capsid antibodies in human immunodeficiency virus-seropositive men: a serological study.

BackgroundSerological study of human papillomavirus (HPV)-antibodies in order to estimate the HPV-prevalence as risk factor for the development of HPV-associated malignancies in human immunodeficiency virus (HIV)-positive men.MethodsSera from 168 HIV-positive men and 330 HIV-negative individuals (including 198 controls) were tested using a direct HPV-ELISA specific to HPV-6, -11, -16, -18, -31 and bovine PV-1 L1-virus-like particles. Serological results were correlated with the presence of HPV-associated lesions, the history of other sexually transmitted diseases (STD) and HIV classification groups.ResultsIn HIV-negative men low risk HPV-antibodies were prevailing and associated with condylomatous warts (25.4%). Strikingly, HIV-positive men were more likely to have antibodies to the high-risk HPV types -16, -18, -31, and low risk antibodies were not increased in a comparable range. Even those HIV-positive heterosexual individuals without any HPV-associated lesions exhibited preferentially antibody responses to the oncogenic HPV-types (cumulative 31.1%). The highest antibody detection rate (88,8%) was observed within the subgroup of nine HIV-positive homosexual men with anogenital warts. Three HIV-positive patients had HPV-associated carcinomas, in all of them HPV-16 antibodies were detected. Drug use and mean CD4-cell counts on the day of serologic testing had no influence on HPV-IgG antibody prevalence, as had prior antiretroviral therapy or clinical category of HIV-disease.ConclusionHigh risk HPV-antibodies in HIV-infected and homosexual men suggest a continuous exposure to HPV-proteins throughout the course of their HIV infection, reflecting the known increased risk for anogenital malignancies in these populations. The extensive increase of high risk antibodies (compared to low risk antibodies) in HIV-positive patients cannot be explained by differences in exposure history alone, but suggests defects of the immunological control of oncogenic HPV-types. HPV-serology is economic and can detect past or present HPV-infection, independently of an anatomical region. Therefore HPV-serology could help to better understand the natural history of anogenital HPV-infection in HIV-positive men in the era of antiretroviral therapy.

Choriocarcinoma and human immunodeficiency virus (HIV) infection: A case report

Abstract.Moodley M, Moodley J. Choriocarcinoma and human immunodeficiency virus (HIV) infection: a case report.The appropriate management of gynecological malignancies in human immunodeficiency virus (HIV)-infected patients is uncertain. Gestational trophoblastic disease is highly curable and occurs predominantly among young females. However, such patients are often immunocompromised and cytotoxic agents may further compromise immunity. This case report demonstrates the successful management of choriocarcinoma in a HIV-infected patient.

Head and neck manifestations of non-Hodgkin's lymphoma in human immunodeficiency virus-infected patients

Non-Hodgkin's lymphoma is the 2nd most common malignancy in human immunodeficiency virus (HIV)-infected patients. However, limited information regarding head and neck manifestations of non-Hodgkin's lymphoma is present in the literature. The aim of this article is to describe the head and neck manifestations of non-Hodgkin's lymphoma in HIV-infected patients and compare it with that seen in noninfected patients. A case-control study was performed including 124 patients with non-Hodgkin's lymphoma presenting over a 5.5-year period to tertiary care center in a metropolitan location. Overall, the anatomic distribution of non-Hodgkin's lymphoma is not altered in the presence of HIV infection with the head and neck region (63%) most often involved overall. However, within the head and neck region, extralymphatic disease is significantly more common in HIV-infected patients (59%) than noninfected patients (33%; P = .001). Central nervous system (CNS) involvement accounts for 41% of head and neck non-Hodgkin's lymphoma in HIV-infected patients, in contrast to only 12% of noninfected patients. High-grade lymphoma (68%) are more common than intermediate (30%) or low-grade disease (2%) in the HIV-infected population, whereas low (24%) and intermediate (60%) grades are more common than high-grade lymphoma (16%) in noninfected patients (P < .001). The large cell immunoblastic type (48%) is the most common subtype in HIV-infected patients, whereas diffuse large-cell type (32%) was most common in HIV-negative patients (P < .05). Survival is significantly poor for HIV-infected patients (P < .05). The impact of HIV infection on survival remain significant even after controlling for the effects of confounding factors. Head and neck involvement with non-Hodgkin's lymphoma occurs in a significant number of HIV-infected patients. Our data show that the distribution and course of non-Hodgkin's lymphoma is unique in HIV-infected patients. A high level of suspicion for non-Hodgkin's lymphoma is required in all cases of head and neck lesions in patients with HIV infection to facilitate management.

Cancer in human immunodeficiency virus-infected children: a case series from the Children's Cancer Group and the National Cancer Institute.

To describe the spectrum of malignancies in human immunodeficiency virus (HIV)-infected children and the clinical outcome of patients with these tumors. We retrospectively surveyed the Children's Cancer Group (CCG) and the National Cancer Institute (NCI) for cases of cancer that occurred between July 1982 and February 1997 in children who were HIV seropositive before or at the time of cancer diagnosis. We used Kaplan-Meier survivorship curves, hazard function estimates, and Cox proportional hazards models to evaluate survival. Sixty-four children (39 boys, 25 girls) with 65 tumors were reported. Thirty-seven children (58%) acquired HIV infection vertically (median age at cancer diagnosis, 4.3 years); 22 children (34%) acquired HIV through transfusion of blood or blood products (median age at cancer diagnosis, 13.4 years). Forty-two children (65%) had non-Hodgkin's lymphoma (NHL). Eleven children (17%) had leiomyosarcomas (or leiomyomas), which are otherwise exceptionally rare in children. Other malignancies included acute leukemia (five children), Kaposi's sarcoma (KS; three children), Hodgkin's disease (two children), vaginal carcinoma in situ (one child), and tracheal neuroendocrine carcinoma (one child). Median survival after NHL diagnosis was 6 months (range, 1 day to 89 months) and after leiomyosarcoma was 12 months (range, 10 days to 19 months). The average monthly death rate after NHL diagnosis was 12% in the first 6 months, which decreased to about 2% thereafter. In contrast, the monthly death rate after leiomyosarcoma diagnosis increased from 5% in the first 6 months to about 20% thereafter. After NHL, leiomyosarcoma is the second leading cancer in children with HIV infection. Both cancers have high mortality rates; improved outcome for NHL, in particular, may depend on earlier diagnosis and therapy.