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AIDS Related Cancers

People with Acquired Immunodeficiency Syndrome (AIDS) may be more susceptible to developing certain types of cancer because their body's natural defences have been weakened. Prior to the AIDS epidemic in the 1990's Kaposi's sarcoma was a relatively rare disease usually seen only in older men or people who had organ transplants, however, increasing incidence of the disease has been associated with the spread of AIDS. Kaposi's sarcoma is a cancer that arises in the cells below the skin or in the mucous membrane lining of the mouth, nose, and anus. Lymphomas (Hodgkin's disease and particularly non-Hodgkin's lymphoma) can also be aids-related, these are cancers of the lymphatic system (part of the immune system). Many chemotherapy drugs used to treat cancer can suppress the immune system. Treatment for cancer in people with AIDS may need to be modified since AIDS has already weakened their immune system.

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HIV/AIDS Related Cancers
Latest Research Publications
General HIV/AIDS Resources
AIDS-Related Lymphoma
Kaposi Sarcoma

HIV/AIDS Related Cancers (6 links)

Latest Research Publications

Lovasik BP, Wang VL, Point du Jour KS, et al.
Visceral Kaposi Sarcoma Presenting as Small Bowel Intussusception: A Rare Presentation and Call to Action.
Am Surg. 2019; 85(7):778-780 [PubMed] Related Publications
Surgical emergencies related to visceral involvement of Kaposi sarcoma (KS) are rare complications of the disease. In this report, we describe a case of visceral KS causing small bowel intussusception in a young, previously undiagnosed human immunodeficiency virus (HIV)-positive patient. Southern surgeons should be particularly attentive to HIV/AIDS-related disease as a cause of surgical pathology, particularly in the southeast, and can play a significant advocacy role for improved access to HIV/AIDS diagnostic and treatment services.

Junfeng L, Lina M, Xinyue C
Autologous hematopoietic stem cell transplantation for human immunodeficiency virus associated gastric Burkitt lymphoma: A case report.
Medicine (Baltimore). 2019; 98(29):e16222 [PubMed] Related Publications
RATIONALE: HIV-related lymphoma, especially non-Hodgkin lymphoma, is one of the most common malignant tumors in HIV/acquired immune deficiency syndrome (AIDS) patients. Autologous hematopoietic stem cell transplantation (AHSCT) for the patients with Burkitt lymphoma (BL) is needed to be further explored.
PATIENT CONCERNS: A 57-year-old man was hospitalized with intermittent pain on upper abdomen and melena for >1 month.
DIAGNOSIS: HIV antibody testing was positive. The upper gastrointestinal endoscopy was performed and histopathology and immunohistochemistry revealed BL.
INTERVENTIONS: Highly effective antiretroviral therapy and sixth cycles of chemotherapy were administered, followed by autologous hematopoietic stem cell transplantation.
OUTCOMES: The patient has had tumor-free survival for >6 years with normal CD4+ T cell counts and HIV viral load below the lowest detection LESSONS:: The patient was treated with AHSCT followed complete remission after chemotherapy and achieved long-term disease-free survival. AHSCT may be a promising way for clinical cure of HIV-related BL.

Kim MS, Park JH, Kim JY, et al.
Upper gastrointestinal bleeding caused by direct invasion of diffuse large B-cell lymphoma into the stomach in a patient with HIV infection: A case report.
Medicine (Baltimore). 2019; 98(28):e16363 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Diffuse large B-cell lymphoma (DLBCL) is the most frequent human immunodeficiency virus (HIV)-related Non-Hodgkin's Lymphoma of the stomach. Although gastrointestinal (GI) bleeding due to primary gastric lymphoma has been previously reported in the literature, there have been no reports of stomach wall involvement of intra-abdominal lymphoma presenting as GI bleeding.
PATIENT CONCERNS: We present a rare case of direct invasion of DLBCL to the stomach wall that presented as upper GI bleeding in a patient with HIV.
DIAGNOSIS: Upper endoscopy showed a large ulcerofungating mass in the lesser curvature of upper stomach body. The computed tomography scan showed an about 22 × 12 cm sized huge mass that invades into the stomach wall in the abdominal cavity. A diagnosis of DLBCL was established after histological examination.
INTERVENTION: The patient was treated with 6 courses of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).
OUTCOMES: The patient achieved a complete response with 6 courses of R-CHOP treatment. No recurrence was observed during the 4-month follow-up period.
LESSONS: Because of the high incidence of lymphoma in patients with HIV, if such patients complain of dyspepsia, epigastric soreness, or melena, malignant tumors, such as lymphomas or stomach cancers, should be suspected. As in this patient, doctors should be aware that intra-abdominal lymphoma can invade into the stomach wall and cause bleeding.

Li R, Li H
Poor prognosis of retroperitoneal mixed extragonadal germ cell tumors in an HIV-infected man with severe immunosuppression and bilateral cryptorchidism: a case report.
BMC Cancer. 2019; 19(1):244 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Nonseminomatous germ cell tumors (NSGCTs) represent one of the main groups of germ cell tumors (GCTs), and they have a more invasive course than seminomatous GCTs. Human immunodeficiency virus (HIV) positivity is considered to be a risk factor for testicular seminoma patients, but reports about HIV-infected individuals with NSGCTs are rare.
CASE PRESENTATION: We report a case of a retroperitoneal mixed extragonadal germ cell tumor in an HIV-infected man who has been diagnosed with bilateral cryptorchidism since birth. A 30-year-old man presented with a large heterogeneously mixed echo mass located in the right lower abdomen according to an abdominal ultrasound; he was HIV-positive and had a low CD4 count of 70 cells/ml in the followed test, which suggested severe immunosuppression, and ultrasound-guided biopsy histology revealed a malignant yolk sac tumor of the testis. First, the patient received combination antiretroviral therapy; then, to relieve his symptoms, an exploratory laparotomy and retroperitoneal neoplasm resection under general anesthesia were performed for subsequent treatment. The postoperative histopathological examination indicated that the patient exhibited malignant mixed GCTs of the undescended testis that were composed predominantly of yolk sac tumors with foci of embryonal cell carcinoma and seminoma; It is a rare type in various GCTs, especially in HIV-infected patients. After the operation, the patient underwent computed tomography follow-up scans at 1 week and 2 weeks, and the results showed that the size of the right inguinal mass gradually increased, which suggested a poor outcome. To limit the growth of the tumors, right inguinal mass resection under local anesthesia was performed 17 days after the initial operation, and pathological examination revealed mixed GCT metastasis. Subsequently, the patient received salvage chemotherapy with a regimen of cisplatin, etoposide, and ifosfamide. Unfortunately, the patient died 1 week after the first cycle of chemotherapy because of severe immunosuppression, a low platelet count and cancer cachexia.
CONCLUSIONS: Because of severe immunosuppression, the treatment of advanced extragonadal NSGCTs in an HIV-infected patient resulted in a poor prognosis. This outcome should be considered in further research, and appropriate management for achieving long-term survival needs to be established.

Rhoades R, Gong J, Palmisiano N, Alpdogan O
Primary central nervous system plasmablastic lymphoma in an HIV-positive patient.
BMJ Case Rep. 2019; 12(3) [PubMed] Related Publications
Plasmablastic lymphoma (PBL) is a rare subtype of diffuse large B-cell lymphoma, highly associated with HIV and Epstein-Barr virus (EBV) infections. It commonly presents in extranodal sites, often an oral mass, but reports of primary central nervous system PBL (PCNSPBL) are exceedingly rare. Here, we report on a 33-year-old man with newly diagnosed HIV infection who presented with acute-onset unilateral visual disturbance and was found to have biopsy-proven PCNSPBL. The neoplastic cells displayed a plasmacytoid appearance, with the expression of CD38 and CD138, and were positive for EBV by in situ hybridisation for EBV-encoded RNA. Systemic workup revealed the presence of Kaposi sarcoma, but no evidence of lymphoma. He is currently being treated with high-dose methotrexate, as well as antiretroviral therapy for his HIV infection, and has achieved a complete response.

Essouma M, Tangie LN, Temgoua MN, et al.
Severe clinical immunodeficiency in a patient with human immunodeficiency virus infection and relatively high CD4 counts: a case report.
J Med Case Rep. 2019; 13(1):86 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The coexistence of neuromeningeal cryptococcosis and Kaposi's sarcoma is not surprising in a patient with human immunodeficiency virus infection and a low CD4 count, although it is rarely described. However, we describe such an association in a patient with human immunodeficiency virus infection and a relatively high CD4 count.
CASE PRESENTATION: A 41-year old Cameroonian woman presented to our hospital with subacute occipital headaches associated with photophobia, blurred vision, phonophobia, projectile vomiting, and tonic seizures. In her past history, there was an human immunodeficiency virus infection known for 12 years, for which she had been taking (with good compliance) tenofovir-lamivudine-efavirenz-based antiretroviral therapy for the same period of time. One month before the consultation, gastric Kaposi's sarcoma had been diagnosed, justifying the treatment with doxorubicin she had received. A clinical examination was unremarkable. A computed tomography scan of her brain was normal, and cerebrospinal fluid analysis revealed Cryptococcus neoformans. Her CD4 count was 353/mm
CONCLUSION: This clinical case shows that the coexistence of neuromeningeal cryptococcosis and gastric Kaposi's sarcoma is possible in all patients with human immunodeficiency virus infection, regardless of CD4 count.

Thay S, Peprah SA, Hur C, et al.
Prevalence of Cervical Dysplasia in HIV-Positive and HIV-Negative Women at the Sihanouk Hospital Center of HOPE, Phnom Penh , Cambodia
Asian Pac J Cancer Prev. 2019; 20(2):653-659 [PubMed] Related Publications
Introduction: There is a high burden of cervical cancer in Cambodia, yet published data on the prevalence of cervical dysplasia and the risk factors contributing to the development of pre-cancerous lesions in Cambodian women is very limited. In addition, as it is well known that HIV positivity increases cervical cancer risk, it is important to quantify the prevalence of cervical dysplasia and carcinoma among Cambodian women living with HIV disease. Methods: A cross-sectional study was conducted with a sample of 499 HIV+ and 501 HIV- Cambodian women at the Sihanouk Hospital Center of HOPE. Visual inspection with 5% acetic acid was the method of screening. Colposcopy was performed on all VIA+ patients, and subsequent treatment followed WHO guidelines. Logistic regression models, stratified by both HIV+ and HIV- groups, were used to assess significant factors associated with having dysplasia. Results: VIA+ results were prevalent in both the HIV+ and HIV- arms of the study. The HIV+ patients were more likely to have a lower age at coitarche, lower weight, 2 or more lifetime sexual partners, two or greater pregnancies, or be unmarried. The estimated prevalence of VIA detected cervical dysplasia was 11% for the entire study sample, 13.4% in the HIV positive (HIV+) group and 8.6% in the HIV negative (HIV-) group (OR: 1.65; 95% CI: 1.10, 2.48; p=0.01). For the HIV+ group, having a history of 4 or more full-term pregnancies (OR: 3.42; 95% CI: 1.01-11.64; p=0.049) was found to be significantly associated with having an increased risk of developing cervical dysplasia in the multivariate model. Conclusion: Cervical dysplasia is prevalent in both HIV positive and negative Cambodian women and a VIA based national screening programs need to be developed and expanded to provide access to affordable and effective treatment for cervical dysplasia and cancers.

Kung TH, Gordon JR, Abdullahi A, et al.
"My husband says this: If you are alive, you can be someone…": Facilitators and barriers to cervical cancer screening among women living with HIV in India.
Cancer Causes Control. 2019; 30(4):365-374 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
PURPOSE: Women living with human immunodeficiency virus (WLWH) have a higher risk of cervical cancer than women without HIV. In addition, women in India experience a high burden of death from cervical cancer. This qualitative study evaluated individual and interpersonal factors influencing cervical cancer screening among WLWH in Surat, India.
METHODS: In-depth interviews were conducted with 25 WLWH and 15 stakeholders in Surat, India. Data were analyzed using directed content analysis to identify individual and intrapersonal barriers and facilitators.
RESULTS: WLWH lacked knowledge and reported being afraid of cervical cancer and cervical cancer screening but were interested in learning more about it. Interpersonal factors influencing cervical cancer screening included receipt or lack of instrumental and emotional family support, interactions with healthcare providers, and receipt or lack of information about cervical cancer and the Pap test from healthcare providers.
CONCLUSION: Widespread public education is necessary to increase awareness of cervical cancer and cervical cancer screening and to encourage family members to support women who wish to obtain screening. Patient- and provider-focused interventions may facilitate the process of providing cervical cancer care to WLWH who are obtaining care in busy public healthcare systems in India.

Klein C, Gonzalez D, Samwel K, et al.
Relationship between the Cervical Microbiome, HIV Status, and Precancerous Lesions.
MBio. 2019; 10(1) [PubMed] Article available free on PMC after 01/04/2020 Related Publications
Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (

Sampath R, Manipadam MT, Nair S, et al.
HIV-associated lymphoma: A 5-year clinicopathologic study from India.
Indian J Pathol Microbiol. 2019 Jan-Mar; 62(1):73-78 [PubMed] Related Publications
Context: Relative risk of non-Hodgkin lymphoma (NHL) in people living with HIV is 60-200 times that of normal population. This is the largest series from India on lymphomas arising in HIV-infected individuals including workup for Epstein-Barr virus (EBV) and human herpesvirus-8 (HHV-8).
Aims: This study aims to ascertain the distribution and detailed clinicopathologic features of lymphoma arising in HIV-infected persons in India.
Settings and Design: The study was done during the period of 2007-2011 in the pathology department of a tertiary care center in South India.
Subjects and Methods: All cases diagnosed as lymphoma in the department of pathology during the study period were identified, and patients with HIV positive by serology were included in the study. Clinical details were obtained from electronic records, slides were reviewed and tissue blocks retrieved, and immunohistochemistry for HHV-8 and in situ hybridization for EBV-encoded RNA was done.
Statistical Analysis Used: Descriptive statistics were done using SPSS software. Kaplan-Meier curves were used to do survival analysis.
Results: Of 3346 patients diagnosed with lymphoma, 73 (2%) were diagnosed to be positive for HIV. About 87.6% of the cases were NHL, of which diffuse large B-cell lymphoma was the most common and plasmablastic lymphoma was the second common subtype. Survival was uniformly poor in 36% of the cases where follow-up was available.
Conclusions: The striking differences from world literature included higher frequency of plasmablastic lymphomas, lack of primary central nervous system lymphomas, and low association with HHV8.

Akhanoba F, Zill-E-Huma R, Pollock R, Edwards SJE
Synovial sarcoma in an HIV-positive pregnant woman and review of literature.
BMJ Case Rep. 2019; 12(1) [PubMed] Related Publications
We present a first case of synovial sarcoma in an HIV-positive pregnant woman. This 28-year-old woman was diagnosed with synovial sarcoma, a high-grade malignant soft tissue sarcoma, involving her left thigh during the first trimester of her pregnancy. She underwent surgical treatment in the form of hip disarticulation at 30 weeks' gestation. She was subsequently delivered by emergency caesarean section (CS) at 34 weeks' gestation when she presented with wound sepsis and a scan revealed static growth in a small for gestational age fetus. Prompt diagnosis and treatment of this aggressive tumour is important and should involve a multidisciplinary approach, with a balanced consideration of the maternal and fetal outcomes.

Althoff KN, Gebo KA, Moore RD, et al.
Contributions of traditional and HIV-related risk factors on non-AIDS-defining cancer, myocardial infarction, and end-stage liver and renal diseases in adults with HIV in the USA and Canada: a collaboration of cohort studies.
Lancet HIV. 2019; 6(2):e93-e104 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
BACKGROUND: Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes.
METHODS: We included participants receiving care in academic and community-based outpatient HIV clinical cohorts in the USA and Canada from Jan 1, 2000, to Dec 31, 2014, who contributed to the North American AIDS Cohort Collaboration on Research and Design and who had validated non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, or end-stage renal disease outcomes. Traditional risk factors were tobacco smoking, hypertension, elevated total cholesterol, type 2 diabetes, renal impairment (stage 4 chronic kidney disease), and hepatitis C virus and hepatitis B virus infections. HIV-related risk factors were low CD4 count (<200 cells per μL), detectable plasma HIV RNA (>400 copies per mL), and history of a clinical AIDS diagnosis. PAFs and 95% CIs were estimated to quantify the proportion of outcomes that could be avoided if the risk factor was prevented.
FINDINGS: In each of the study populations for the four outcomes (1405 of 61 500 had non-AIDS-defining cancer, 347 of 29 515 had myocardial infarctions, 387 of 35 044 had end-stage liver disease events, and 255 of 35 620 had end-stage renal disease events), about 17% were older than 50 years at study entry, about 50% were non-white, and about 80% were men. Preventing smoking would avoid 24% (95% CI 13-35) of these cancers and 37% (7-66) of the myocardial infarctions. Preventing elevated total cholesterol and hypertension would avoid the greatest proportion of myocardial infarctions: 44% (30-58) for cholesterol and 42% (28-56) for hypertension. For liver disease, the PAF was greatest for hepatitis C infection (33%; 95% CI 17-48). For renal disease, the PAF was greatest for hypertension (39%; 26-51) followed by elevated total cholesterol (22%; 13-31), detectable HIV RNA (19; 9-31), and low CD4 cell count (13%; 4-21).
INTERPRETATION: The substantial proportion of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes that could be prevented with interventions on traditional risk factors elevates the importance of screening for these risk factors, improving the effectiveness of prevention (or modification) of these risk factors, and creating sustainable care models to implement such interventions during the decades of life of adults living with HIV who are receiving care.
FUNDING: National Institutes of Health, US Centers for Disease Control and Prevention, the US Agency for Healthcare Research and Quality, the US Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long Term Care, and the Government of Alberta.

Chen J, Mehraj V, Szabo J, et al.
Multiple remissions of extracavitary primary effusion lymphoma treated with a single cycle of liposomal doxorubicin in a patient infected with HIV.
Curr Oncol. 2018; 25(6):e592-e596 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
Primary effusion lymphoma (pel) is a rare human herpesvirus 8 (hhv8)-related large B cell lymphoma with plasmablastic, immunoblastic, or anaplastic features that often carries a poor prognosis. This lymphoma occurs mainly in patients with hiv infection, most often with Epstein-Barr virus (ebv) co-infection, and usually presents as body cavity effusions or, less commonly, as extracavitary lesions without effusion (ec-pel). Chemotherapeutic treatment options are limited and require concurrent antiretroviral therapy (art). Here, we report the case of an adult patient with hiv infection and chronic hepatitis E virus (hev) co-infection who had low CD4 T cell recovery after years of art. The patient then developed a cutaneous ec-pel which rapidly regressed after 1 cycle of liposomal doxorubicin (ld) for his Kaposi sarcoma (ks) before treatment with chop chemotherapy. He had previously received numerous cycles of ld for cutaneous ks over 2 years. Because of the patient's low CD4 T cell count, hev co-infection, and earlier unexpected remission of ec-pel before chop, the patient opted for a single trial of ld before other options. Surprisingly, he experienced a complete remission lasting 18 months. Subsequently, his ec-pel relapsed twice at 31 and at 41 months after the initial diagnosis. Upon recurrence, a similar single cycle of ld was given, which again induced remission. The patient today is in complete remission after a total of 4 ld infusions over 54 months. This patient represents a unique case of hiv-with-hhv8-related, ebv-negative ec-pel with chronic hev coinfection, in which rapid remission was achieved after a single cycle of ld, suggesting an antiviral response in addition to the chemotherapeutic effect.

Min H, Yang J, Wang S, et al.
Remission of HIV-related naïve and high-risk Burkitt's lymphoma treated by autologous stem cell transplantation plus cART.
Stem Cell Res Ther. 2018; 9(1):353 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
A 27-year-old male with HIV-associated naïve and high-risk Burkitt's lymphoma sequentially received short-term, high-dose non-myeloablative chemotherapy and autologous CD34-positive stem cell transfusion in the setting of combined antiretroviral therapy (cART). Prompt hematopoietic recovery was observed after 2 weeks and clinical remission from Burkitt's lymphoma within approximately 30 months after transplantation. The HIV RNA load was inhibited persistently, and drug resistance was not observed. The CD4+ T cell count approached 323 cells/μL in a recent follow-up study. This case suggests that the use of intensive non-myeloablative chemotherapy with transplantation, combined with antiretroviral therapy, in HIV-related naive and high-risk Burkitt's lymphoma was tolerated and safe.

Kobayashi T, Sigel K, Kalir T, et al.
Anal Cancer Precursor Lesions in HIV-Infected Persons: Tissue Human Papillomavirus Type Distribution and Impact on Treatment Response.
Dis Colon Rectum. 2019; 62(5):579-585 [PubMed] Related Publications
BACKGROUND: Data on tissue distribution of human papillomavirus types in anal high-grade squamous intraepithelial lesions are limited and the impact on treatment outcomes poorly understood.
OBJECTIVE: We aimed to investigate potential predictors of treatment failure after electrocautery ablation, including human papillomavirus type(s) isolated from index lesions.
DESIGN: This was a retrospective cohort study.
SETTINGS: The study was conducted at a tertiary academic referral center in New York City.
PATIENTS: Seventy-nine HIV-infected patients with a diagnosis of anal high-grade squamous intraepithelial lesions between January 2009 and December 2012 were included, and genomic DNA was extracted from biopsy tissue.
MAIN OUTCOME MEASURES: The prevalence of human papillomavirus types in index lesions and surveillance biopsies after electrocautery ablation were analyzed to evaluate treatment response.
RESULTS: Of 79 anal high-grade squamous intraepithelial lesions, 71 (90%) tested positive for ≥1 human papillomavirus type; 8 (10%) had no human papillomavirus detected. The most common type was 16 (39%), followed by 33 (15%). Human papillomavirus type 18 was seen in 3%. Sixty-one patients (77%) underwent electrocautery ablation and had subsequent surveillance biopsies. Surveillance biopsies yielded benign findings or low-grade squamous intraepithelial lesions in 31 (51%) of 61 and recurrent high-grade squamous intraepithelial lesions in 30 (49%) of 61 patients (mean follow-up: 35 mo). Ablation response did not differ significantly based on baseline demographics, smoking history, history of anogenital warts, mean CD4 T-cell count, antiretroviral-therapy use, and HIV viral load (<50 copies/mL). The recurrence of high-grade lesions was not significantly associated with high-risk human papillomavirus types detected in index lesions.
LIMITATIONS: Human papillomavirus genotyping in surveillance biopsies was not performed.
CONCLUSIONS: Anal high-grade squamous intraepithelial lesions in HIV-infected patients contain a wide range of human papillomavirus types, and individual lesions commonly harbor multiple types concomitantly. Recurrence of anal high-grade squamous intraepithelial lesions after electrocautery ablation occurs frequently and is not affected by high-risk human papillomavirus types. See Video Abstract at http://links.lww.com/DCR/A833.

Semango GP, Charles RM, Swai CI, et al.
Prevalence and associated risk factors for Kaposi's sarcoma among HIV-positive patients in a referral hospital in Northern Tanzania: a retrospective hospital-based study.
BMC Cancer. 2018; 18(1):1258 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
BACKGROUND: Kaposi's sarcoma (KS) is a multifocal angioproliferative tumor involving blood and lymphatic vessels, caused by Human Herpes Virus-8 (HHV-8). KS is an important AIDS-defining tumor with high prevalence in Sub-Saharan Africa, including Tanzania which has high HIV and HHV-8 sero-prevalence. It is critically important to monitor the prevalence of AIDS-defining tumors, such as KS, in the age of HIV/AIDS. We studied the prevalence of KS and associated risk factors among HIV-positive patients at Kilimanjaro Christian Medical Centre (KCMC), a referral hospital in northern Tanzania, over the period from January 2012 to December 2015.
METHODS: This was a retrospective hospital-based cross-sectional study to determine the prevalence of KS among HIV/AIDS patients between 2012 and 2015. The study included 1100 HIV patients' data which were collected at the Infectious Disease Clinic (IDC) from patients' files. Stata version 13 (StataCorp LP, Texas 77,845 USA) was used for all statistical analyses. The prevalence of KS was calculated across levels of a number of categorical variables. Logistic regression was performed to determine relative risk of KS for all characteristics. We included all variables with p-values ≤10% in the multivariate analysis, including ART use, as this is considered to have an influence on KS. In the multivariate analysis, statistical significance was established based on a two-tailed p-value ≤5%. All patients' notes were kept confidential as per the Helsinki declaration.
RESULTS: Our results revealed a 4.6% prevalence of KS at KCMC hospital, between January 2012 and December 2015, 51(4.6%) patients were diagnosed with KS out of 1100 HIV-positive patients. The study further revealed that KS in HIV patients was most associated with low CD4 cell count (less than or equal to 200 cells/μl). Moreover, women were more likely than men to diagnosed with KS, with higher odds significantly associated with KS (OR 0.42, p < 0.009). Increased age, above 35 years, among the HIV seropositive patients was significantly associated with KS (OR 25.67, p < 0.007). HIV patients who were none smokers were more likely to suffer from KS compared to HIV smokers (OR 0.41, p < 0.010).
CONCLUSION: KS remains a common malignant vascular tumor commonly associated with HIV/AIDS in Tanzania. Our study highlights the need for continued efforts to combat HIV, as well as associated diseases such as KS. Continued availability of ART (Anti-Retroviral Therapy) to HIV/AIDS patients, and test reagents for CD4 cell count and viral load determination are important measures to alleviate the suffering of these patients. Furthermore, studies to gather more evidence on ART resistance are highly needed to guide treatment choices.

Goldstein RH, DeCaprio JA
Merkel Cell Carcinoma in the HIV-1/AIDS Patient.
Cancer Treat Res. 2019; 177:211-229 [PubMed] Related Publications
Merkel cell carcinoma (MCC) is a highly aggressive, primary neuroendocrine cancer of the skin. The majority of MCC cases are associated with the recently discovered Merkel cell polyomavirus (MCPyV), while the remaining are caused by ultraviolet (UV) light-induced mutations from excessive sunlight exposure. The risk of developing MCC is much higher in the white population relative to all other races. Approximately 10% of all patients with MCC have some form of immunosuppression including HIV-1/AIDS, chronic inflammatory conditions, solid organ transplantation, or hematological malignancies. The age of onset of MCC is lower and the mortality is higher in immunosuppressed individuals than in immune-competent patients. It is plausible that HIV-1/AIDS predisposes to virus-positive MCC, but it should be noted that HIV-1/AIDS increases the risk for developing of UV-induced skin cancers such as cutaneous squamous cell carcinoma and basal cell carcinoma and therefore may also increase the risk for virus-negative MCC. Surgical management is considered standard of care for localized Merkel cell carcinoma with current recommendations advising a wide local excision of the lesion. Most international guidelines support the use of local adjuvant radiotherapy coupled with tumor staging to improve the frequency of cure. For advanced, metastatic, and recurrent MCC, checkpoint blockade inhibitors targeting PD-1 and PD-L1 have shown remarkable activity including durable long-term. MCC in patients living with HIV-1/AIDS are treated with similar modalities as HIV-1 uninfected individuals with MCC.

Mondal P, Lim HJ, Ohtn Cohort Study Team
The Effect of MSM and CD4+ Count on the Development of Cancer AIDS (AIDS-defining Cancer) and Non-cancer AIDS in the HAART Era.
Curr HIV Res. 2018; 16(4):288-296 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
BACKGROUND: The HIV epidemic is increasing among Men who have Sex with Men (MSM) and the risk for AIDS defining cancer (ADC) is higher among them.
OBJECTIVE: To examine the effect of MSM and CD4+ count on time to cancer AIDS (ADC) and noncancer AIDS in competing risks setting in the HAART era.
METHOD: Using Ontario HIV Treatment Network Cohort Study data, HIV-positive adults diagnosed between January 1997 and October 2012 having baseline CD4+ counts ≤ 500 cells/mm3 were evaluated. Two survival outcomes, cancer AIDS and non-cancer AIDS, were treated as competing risks. Kaplan-Meier analysis, Cox cause-specific hazards (CSH) model and joint modeling of longitudinal and survival outcomes were used.
RESULTS: Among the 822 participants, 657 (79.9%) were males; 686 (83.5%) received anti-retroviral (ARV) ever. Regarding risk category, the majority (58.5%) were men who have Sex with men (MSM). Mean age was 37.4 years (SD = 10.3). In the multivariate Cox CSH models, MSM were not associated with cancer AIDS but with non-cancer AIDS [HR = 2.92; P = 0.055, HR = 0.54; P = 0.0009, respectively]. However, in joint models of longitudinal and survival outcomes, MSM were associated with cancer AIDS but not with non-cancer AIDS [HR = 3.86; P = 0.013, HR = 0.73; P = 0.10]. CD4+ count, age, ARV ever were associated with both events in the joint models.
CONCLUSION: This study demonstrates the importance of considering competing risks, and timedependent biomarker in the survival model. MSM have higher hazard for cancer AIDS. CD4+ count is associated with both survival outcomes.

Baldur-Felskov B, Mwaiselage J, Faber MT, et al.
Factors associated with a cervical high-grade lesion on cytology or a positive visual inspection with acetic acid among more than 3300 Tanzanian women.
Trop Med Int Health. 2019; 24(2):229-237 [PubMed] Related Publications
OBJECTIVES: Cervical cancer screening by visual inspection with acetic acid (VIA) is a widely used alternative to cytology in developing countries. This study aimed to evaluate risk factors associated with a positive VIA test and with cervical high-grade lesions on cytology.
METHODS: We conducted a large cross-sectional study among 3339 women from urban and rural Tanzania. Study participants were interviewed about socio-demographic, reproductive and lifestyle factors. Blood samples were tested for HIV, and a gynaecological examination was performed. Human papillomavirus (HPV) status was determined by Hybrid Capture 2, and HPV genotyping was done using the LiPA Extra test. We used multivariable logistic regression to estimate adjusted odds ratios (ORs) and confidence intervals (CIs).
RESULTS: The strongest risk factors for VIA positivity were positivity to HIV (OR = 3.48; 95% CI: 2.34-5.17) or to high-risk HPV (HrHPV) (OR = 1.97; 95% CI: 1.37-2.85). HrHPV was by far the strongest predictor of high-grade cytology (OR = 110.1; 95% CI: 50.4-240.4), while there was no significant association with HIV in the multivariable analysis (OR = 1.27; 95% CI: 0.78-2.08). After adjustment for HrHPV, HIV and age, the risk of high-grade cytology also increased with increasing age, number of births and low body mass index (BMI), while high BMI decreased the risk of VIA positivity.
CONCLUSIONS: Infection with HrHPV is a major risk factor for high-grade cytology, while VIA positivity is associated with HIV and to a lesser extent with HrHPV.

Peprah S, Coleman JS, Rositch AF, et al.
Utilization of Pap testing among women living with HIV enrolled in primary care in Baltimore, Maryland: A 10-year longitudinal study, 2005-2014.
Papillomavirus Res. 2018; 6:52-57 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
Frequent Pap testing is recommended among women living with HIV (WLWH) due to their elevated risk for cervical cancer. However, there are few recent longitudinal evaluations of utilization and determinants of Pap testing among WLWH. Medical and pathology records of WLWH seen at Johns Hopkins Hospital between 2005 and 2014 were assessed using Prentice, Williams, Peterson models. Of 554 WLWH in care for ≥ 18 months, 79% received Pap testing, however only 11% consistently received Pap testing at the recommended interval. Some women (5%) were consistently under-screened (tested at longer intervals) and 21% did not receive any Pap testing at during follow-up. WLWH with decreased likelihood of screening included older women, injection drug users, whites and those who had lived for longer with HIV. In contrast, only women with a prior abnormal Pap result were more likely to receive Pap testing. CD4 cell count and health insurance were not significant determinants. Although many WLWH in care received Pap testing, some WLWH were unscreened or underscreened. Determinants of Pap testing for WLWH include socio-demographic factors and a prior abnormal result; these present potential targets in an urban HIV care setting for closer monitoring and directed interventions to improve utilization among WLWH.

Kim SE, Jung Y, Oh TH, et al.
Case report: dual primary AIDS-defining cancers in an HIV-infected patient receiving antiretroviral therapy: Burkitt's lymphoma and Kaposi's sarcoma.
BMC Cancer. 2018; 18(1):1080 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
BACKGROUND: The incidence of AIDS-defining cancers (ADCs) has decreased markedly in the era of highly active antiretroviral therapy (HAART). The occurrence of two ADCs is rare in people living with HIV or AIDS (PWHA) who are severely immunosuppressed or have incomplete virologic suppression.
CASE PRESENTATION: We report a case of dual primary ADCs, especially NHL followed by KS, in a 70-year-old HIV-infected man who was on antiretroviral therapy and had successful virologic suppression. During HAART, he presented with generalized myalgia and abdominal pain. Multiple liver masses were detected and a biopsy revealed Burkitt's lymphoma. After three cycles of anticancer chemotherapy with a favorable response, he was diagnosed with cytomegalovirus retinitis and the anti-cancer chemotherapy was discontinued. Despite successful virologic suppression with HAART, human herpes virus-8 associated Kaposi's sarcoma was diagnosed in his right thigh. He underwent radiation therapy.
CONCLUSION: These findings suggest that multiple ADCs can occur in PWHA who are receiving HAART and have successful virologic suppression. Healthcare providers caring for PWHA should maintain vigilance for the development of a broad spectrum of cancers.

Wilkin TJ
Human papillomavirus-related malignancies in HIV infection: anal and oropharyngeal cancers.
Top Antivir Med. 2018; 26(3):85-88 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
Human papillomavirus (HPV)-related cancers, including anal cancer and oropharyngeal cancer, occur more frequently in individuals living with HIV infection than in the general population. Strategies for prevention among individuals with HIV infection include HPV vaccination, anal cancer screening programs, and early initiation of antiretroviral therapy (ART). HPV vaccination is not yet optimally used; a stronger and more persistent effort is needed to increase vaccination rates. Although anal cancer screening is not recommended by all authorities, there is a least some evidence that screening and treatment of anal high-grade squamous intraepithelial lesions may prevent progression to cancer. However, more definitive evidence is needed. Early initiation of ART reduces the risk of infection-related cancers, with some evidence of benefit in preventing HPV-associated cancer in individuals with HIV infection. This article summarizes a presentation by Timothy J. Wilkin, MD, MPH, at the IAS-USA continuing education program held in Los Angeles, California in April 2018.

Matenge TG, Mash B
Barriers to accessing cervical cancer screening among HIV positive women in Kgatleng district, Botswana: A qualitative study.
PLoS One. 2018; 13(10):e0205425 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
BACKGROUND: Low and middle-income countries have a greater share of the cervical cancer burden, but lower screening coverage, compared to high-income countries. Moreover, screening uptake and disease outcomes are generally worse in rural areas as well as in the HIV positive population. Efforts directed at increasing the screening rates are important in order to decrease cancer-related morbidity and mortality. This study aimed to explore the barriers to women with HIV accessing cervical cancer screening in Kgatleng district, Botswana.
METHODS: A phenomenological qualitative study utilising semi-structured interviews with fourteen HIV positive women, selected by purposive sampling. The interviews were transcribed verbatim and the 5-steps of the framework method, assisted by Atlas-ti software, was used for qualitative data analysis.
RESULTS: Contextual factors included distance, public transport issues and work commitments. Health system factors highlighted unavailability of results, inconsistent appointment systems, long queues and equipment shortages and poor patient-centred communication skills, particularly skills in explanation and planning. Patient factors identified were lack of knowledge of cervical cancer, benefits of screening, effectiveness of treatment, as well as personal fears and misconceptions.
CONCLUSION: Cervical cancer screening was poorly accessed due to a weak primary care system, insufficient health promotion and information as well as poor communication skills. These issues could be partly addressed by considering alternative technology and one-stop models of testing and treating.

Cajas-Monson LC, Ramamoorthy SL, Cosman BC
Expectant Management of High-Grade Anal Dysplasia in People with HIV: Long-term Data.
Dis Colon Rectum. 2018; 61(12):1357-1363 [PubMed] Related Publications
BACKGROUND: Both ablation and expectant management of high-grade squamous intraepithelial lesions have been proposed. Expectant management would be reasonable if 1) the rate of high-grade squamous epithelial lesion progression to anal squamous cell carcinoma were low, and 2) anal squamous cell carcinoma arising under surveillance had a better prognosis than anal squamous cell carcinoma presenting without an identified precursor.
OBJECTIVE: This study aims to quantify aspects of high-grade squamous epithelial lesion/anal squamous cell carcinoma clinical evolution in a surgical practice.
DESIGN: This is a retrospective cohort study.
SETTINGS: This study was performed in 1 colorectal surgeon's practice over a 20-year period.
PATIENTS: Consecutive patients with high-grade squamous intraepithelial lesion and anal squamous cell carcinoma were included.
MAIN OUTCOME MEASURES: We looked at the rate and timing of progression to anal squamous cell carcinoma, and the stage, treatment, and outcome of anal squamous cell carcinoma. We reviewed a comparison group of HIV-positive patients presenting de novo with anal squamous cell carcinoma (no prior history of high-grade squamous intraepithelial lesion).
RESULTS: With consideration of only HIV-positive patients, 341 patients had a mean 5.6 years follow-up from high-grade squamous intraepithelial lesion diagnosis to the most recent documented anal examination. Twenty-four of these surveillance patients developed anal squamous cell carcinoma, yielding a progression rate of 1.3% per patient-year. Mean follow-up was 7.3 years from the initial cancer diagnosis to the most recent contact. Forty-seven patients who presented de novo with anal squamous cell carcinoma developed 74 lesions, with a mean follow-up of 5.7 years after initial diagnosis. This de novo group had higher anal squamous cell carcinoma-specific mortality (3% per patient-year vs 0.05%). Our study did not show a significantly higher rate of high stage (stage III or IV) at anal squamous cell carcinoma diagnosis in the de novo group in comparison with the surveillance group (25.5% vs 8.3% (p = 0.09)).
LIMITATIONS: This study was retrospective in nature and had a predominately male population.
CONCLUSIONS: The progression of untreated high-grade squamous intraepithelial lesion to anal squamous cell carcinoma approximates 1% per patient-year. Anal squamous cell carcinoma developing under surveillance tends to be of an earlier stage and to require fewer major interventions than anal squamous cell carcinoma presenting de novo. Cancer-specific mortality was lower for malignancies that developed under surveillance. We suggest that expectant management of patients with high-grade squamous intraepithelial lesion is a rational strategy for preventing anal cancer morbidity. See Video Abstract at http://links.lww.com/DCR/A699.

Laher AE, Ebrahim O
HTLV-1, ATLL, severe hypercalcaemia and HIV-1 co-infection: an overview.
Pan Afr Med J. 2018; 30:61 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
HIV and HTLV (Human T-ymphotropic Virus) are the only known retroviruses responsible for causing infection in humans. HTLV-1 and HIV-1 are frequent co-pathogens, however, despite its potential for accelerated progression of HIV disease and the risk of developing adult T-cell lymphoma/leukemia (ATLL), HTLV-1 is seldom considered for investigation in the HIV-1 positive individual. Severe/refractory hypercalcaemia, unresponsive to conventional calcium lowering therapy may complicate up to 70% of cases of ATLL. In addition, HTLV-1 and ATLL have both been associated with a rise in dysfunctional CD4 lymphocytes, thereby conveying a false sense of immune competence in the HIV-1 infected individual.

Gheorghiță V, Conea IF, Radu AMC, et al.
Epidemiological trends and therapeutic challenges of malignancies in adult HIV-1-infected patients receiving combination antiretroviral therapy in a tertiary hospital from Romania: An observational retrospective study.
J Infect Public Health. 2019 Mar - Apr; 12(2):182-189 [PubMed] Related Publications
BACKGROUND: Malignancies have become a leading cause of morbidity and mortality in people living with HIV (PLHIV). The primary endpoint of our study was to describe the epidemiology of acquired immunodeficiency syndrome (AIDS)-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs). Epidemiological disparities, mortality predictors and survival analysis within the two groups of patients were key secondary endpoints.
METHODS: We retrospectively evaluated all adult PLHIV with histopathologically proven cancers registered from 2010 to 2016 in the "Matei Balș" National Institute for Infectious Diseases, Bucharest, Romania.
RESULTS: 110 eligible patients have been included in the study. The incidence of ADCs decreased from 1.6% in 2010 to 0.3% in 2016, unlike NADCs which remained fairly stable over time (0.3%). The higher CD4 count and lower HIV-RNA level at the cancer diagnosis were associated with prolonged survival in ADCs group, but not in NADCs group. The mean CD4 count was 449/mm
CONCLUSIONS: A good therapeutic control of HIV infection at the diagnosis of ADCs was associated with better survival, emphasizing the key role of the effective cART in the management of HIV-associated cancers.

Sinha S, Agarwal A, Gupta K, et al.
Prevalence of HIV in Patients with Malignancy and of Malignancy in HIV Patients in a Tertiary Care Center from North India.
Curr HIV Res. 2018; 16(4):315-320 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
BACKGROUND AND OBJECTIVES: People living with HIV/AIDS are at an increased risk of developing cancer. The goals of this study were to obtain data on the prevalence of HIV in the cancer population and vice versa at a major tertiary cancer and HIV center in North India.
METHODS: This cross-sectional study was conducted over a 3-year period from July 2013 to June 2016, wherein successive HIV positive patients from an anti-retroviral therapy (ART) center were screened for malignancy. Simultaneously, successive cancer patients at the cancer center were screened for HIV. Baseline demographic details, risk factors, and laboratory investigations were obtained for all the patients.
RESULTS: Among the 999 HIV-positive patients at the ART center, the prevalence of malignancy was 2% (n=20; 95% confidence interval (CI) 1.13, 2.87). Among the 998 patients with a malignancy, the prevalence of HIV infection was 0.9% (n=9; 95% CI 0.31, 1.49). Weight loss, loss of appetite, and fever were the most common symptoms in patients with HIV and cancer. Among 29 patients with HIV and cancer, AIDS-defining cancer was found in 19 patients; non-Hodgkin's lymphoma was the most common malignancy reported (n=13).
INTERPRETATION AND CONCLUSION: There is a low prevalence of HIV in cancer patients as well as a low prevalence of cancer in HIV patients. AIDS-defining cancers remain much more common than non-AIDS-defining cancers. With the increased coverage of ART, it is expected that non-AIDSdefining cancers will increase, as is evident from data from more developed countries.

Hijlkema SH, van Kampen JJA, Voermans JJC, et al.
A longitudinal and cross-sectional study ofEpstein-Barr virus DNA load: a possible predictor of AIDS-related lymphoma in HIV-infected patients.
Infect Dis (Lond). 2018 Nov - Dec; 50(11-12):847-852 [PubMed] Related Publications
INTRODUCTION: HIV-infected patients are more than 100-fold greater at risk for developing malignant AIDS-related lymphoma (ARL) compared to the general population. Most ARLs are EBV related. The main purpose of this study was to investigate whether a high peak EBV DNA load in HIV-infected patients is predictive of ARL, including classical Hodgkin lymphoma.
METHODS: From an ongoing prospective HIV positive cohort study, we conducted a case-control study between 2004 and 2016 among patients from whom at least one EBV DNA load in serum or plasma was available. We compared peak EBV DNA load between patients with (49 cases) and without ARL (156 controls).
RESULTS: The geometric mean of the peak EBV DNA load measured before diagnosis of malignant lymphoma was 52,565 IU/mL in EBER-positive lymphoma patients vs. 127 IU/mL in controls (p < .001). Patients with EBV DNA loads >100,000 IU/mL have an increased risk for diagnosis of malignant lymphoma compared to patients with EBV DNA loads ≤100,000 IU/mL (adjusted OR 12.53; 95%CI: 4.08; 38.42). In the longitudinal study, including 13 patients with at least three left-over plasma samples available for retesting, measurements of EBV-DNA during the preceding 12 months proved to be of poor value for predicting subsequent lymphoma diagnosis.
CONCLUSIONS: A EBV DNA load >100,000 IU/mL can be useful in clinical setting to accelerate time to diagnosis and treatment. EBV-DNA loads in samples taken during the preceding year of ARL diagnosis showed to be of poor predictive value.

Adams TS, Cuello MA
Cancer of the vagina.
Int J Gynaecol Obstet. 2018; 143 Suppl 2:14-21 [PubMed] Related Publications
Diagnosis of a primary vaginal cancer is rare because most of these lesions will be metastatic from another primary site. Although cancer of the vagina is more common in postmenopausal women, an increase in young women being diagnosed with primary vaginal cancer has been reported, especially in countries with a high HIV prevalence. This will be associated with persistence of high-risk HPV infection. The emphasis should be on primary prevention with prophylactic HPV vaccination. Once there is a suspicion of a primary vaginal cancer, this should be confirmed histologically with biopsy. Staging has been done clinically, similar to cervical cancer; however, there is a role for imaging in assisting with staging as this is often a difficult assessment. Treatment should be individualized and depends on stage as well as histologic subtype. It is prudent to refer cases to centers of excellence with experience in dealing with this rare gynecological cancer.

Lawal IO, Ankrah AO, Mokoala KMG, et al.
Prognostic Value of Pre-treatment F-18 FDG PET Metabolic Metrics in Patients with Locally Advanced Carcinoma of the Anus with and without HIV Infection.
Nuklearmedizin. 2018; 57(5):190-197 [PubMed] Related Publications
AIM: To investigate the prognostic value of F-18 FDG PET metabolic parameters in patients with anal carcinoma with and without human immunodeficiency virus infection (HIV).
METHODS: Maximum standardized uptake value (SUV
RESULTS: We studied 33 patients including 21 HIV-infected individuals, mean age = 46.06 ± 12.59, female = 16, males = 17. Median CD4 count among HIV-infected patients was 400.50 cells/mm
CONCLUSION: HIV-infected patients are diagnosed with ASSC at a younger age compared with HIV-uninfected patients. F-18 FDG PET metabolic metrics especially MTV predicts overall survival in patients with ASCC. There is no difference in the overall survival of HIV-infected and HIV-uninfected patients treated similarly for ASSC. ZIEL:: Die Untersuchung der prognostischen Bedeutung der F-18 FDG PET metabolischen Aktivität bei HIV-negativen und positiven Analkarzinom-Patienten.
METHODEN: Bestimmt wurden maximale standardisierten Uptake-Werte (SUV
ERGEBNISSE: Wir untersuchten 33 Patienten, davon 21 HIV-Infizierte, mittleres Alter = 46,06 ± 12,59, Frauen = 16, Männer = 17. Die mediane CD4-Zahl unter den HIV-Patienten war 400,50 Zellen/mm
SCHLUSSFOLGERUNGEN: HIV-infizierte Patienten werden in jüngeren Jahren mit ASSC diagnostiziert im Vergleich zu HIV-negativen Patienten. F-18 FDG PET metabolische Aktivität, insbesondere MTV, kann das Gesamtüberleben von Patienten mit ASCC vorhersagen. Es gibt keinen Unterschied im Gesamtüberleben von HIV-infizierten und HIV-negativen Patienten bei gleicher Therapie des ASSC.

General HIV/AIDS Resources (4 links)

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