Social behavioral correlates of Kaposi sarcoma-associated herpesvirus infection among Han and Uygur populations in Xinjiang, China.

BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) is endemic in Xinjiang, China and its prevalence varies considerably across ethnic groups. The current study explored the prevalence and correlates of KSHV infection among Han and Uygur populations in Xinjiang. METHODS: A cross-sectional study, including 282 Han ethnicity and 312 Uygur, was conducted in Xinjiang, China. All participants underwent face to face questionnaire interview. Plasma samples were collected and screened for KSHV infection using immunofluorescence assay. Univariate and multivariate analyses were conducted to examine the correlates of KSHV seropositivity. RESULTS: The KSHV seroprevalence was 41.6% (95% confidence interval [CI], 37.6-45.6) overall and was higher in the Uygur group (59.9%; 95% CI, 54.3-65.4) than the Han group (21.3%; 95% CI, 16.6-26.5). A significant difference in the geometric mean titer (GMT) of the KSHV antibodies was detected between the Uygur and Han groups (158.2; interquartile range [IQR], 80-320 vs 89.1; IQR, 40-160; P < 0.001). After adjusting for potential confounders, Uygur ethnicity (odds ratios [OR], 5.96; 95% CI, 4.05-8.90), age greater than or equal to 50 years (OR, 1.84; 95% CI, 1.24-2.77), and preference for meat diet (OR, 2.15; 95% CI, 1.05-4.46) were significantly associated with increased odds of KSHV seropositivity. CONCLUSION: The study demonstrated high prevalence and correlates of KSHV infection in both Han and Uygur populations in Xinjiang, China. There is an urgent need for programmatic adaptation to address primary prevention interventions of KSHV infection in this endemic region.

Mitochondrial haplogroups and control region polymorphisms in Kaposi's sarcoma patients.

Inflammation and reactive oxygen species (ROS) production have recently considered as key mechanisms in the pathogenesis of Kaposi's sarcoma (KS). Since mitochondria are the major source of ROS production, this organelle may play a main role in KS development. However, there are no studies on mtDNA variations and haplogroups in this area. The focus of this study was to investigate the mtDNA variants and haplogroups in KS patients and their relationship to tumor development. To address this, we have genotyped mtDNA in 45 Iranian KS patients and 48 age and sex-matched Iranian controls. A strong positive correlation was observed between UK cluster and decreased risk of KS. Our results suggest that the UK cluster might be a protective haplogroup for KS development. It is probably superhaplogroup UK, with lower ATP and ROS production, may prevent KSHV reactivation from latent to lytic phase that is essential for KS development.

A case of Kaposi sarcoma in an immunocompetent, heterosexual Irish man: a discussion of etiology and viral transmission.

Four types of Kaposi sarcoma (KS) have been described, all of which are caused by human herpesvirus-8 (HHV-8).  The incidence of KS in the United States is highest among HIV-positive homosexual men and elderly men of Eastern European, Jewish, or Mediterranean descent. However, few reports describe KS in HIV-negative, immunocompetent heterosexual men in the United States. HHV-8 is transmitted largely via saliva and close sexual contact, whereas there are only a handful of reports of transmission via blood and blood products. We report a case of an HIV-negative, immunocompetent heterosexual man who acquired KS via blood transfusion. A 77-year-old immunocompetent, monogamously heterosexual, HIV-negative Irish man presented with a biopsy-proven KS lesion on the right thigh. Past surgical history included a coronary artery bypass graft, during which he received a blood transfusion from an unknown donor source.  His ecchymotic KS lesions progressed while on doxycycline, intralesional vinblastine, and topical anti-angiogenic medications.  The patient eventually achieved stabilization of KS lesions with acitretin. Our case report emphasizes the need to characterize the phenotype and transmission route of HHV-8 in heterosexual, immunocompetent patients in geographic regions with low HHV-8 seroprevalence.

Incidence of primary skin cancer after organ transplantation: An 18-year single-center experience in Korea.

BACKGROUND: Skin cancer is the most common malignancy to arise after organ transplantation in Caucasians, but limited data are available on its incidence in Asian transplant recipients. OBJECTIVE: We sought to assess the incidence of skin cancer after organ transplantation in a Korean cohort. METHODS: A cohort study was conducted to determine the incidence and risk factors for skin cancers among kidney, liver, heart, or pancreas transplant recipients, treated at the Asan Medical Center in Seoul, Korea. RESULTS: The cumulative incidences of skin cancer were 0.70% at 5 years, 1.66% at 10 years, and 2.31% at 15 years. For all skin cancers, squamous cell carcinoma, basal cell carcinoma, and Kaposi sarcoma, the standardized incidence ratios between the recipients and the Korean general population were 30.9 (95% confidence interval, 12.4-63.6), 61.9 (12.8-180.8), 11.9 (0.3-66.1), and 565.2 (68.4-2041.6) after the end of the fifth posttransplantation year, respectively. LIMITATIONS: We cannot exclude the possibility of both the underestimation because of potential missing cases and the overestimation because of the ascertainment bias. CONCLUSION: The incidence of posttransplantation skin cancer is very low in Korean patients. However, the risk of skin cancer in organ transplant recipients may be considerably higher than that in the Korean general population.

Seroprevalence and risk factors of Kaposi's sarcoma-associated herpesvirus infection among the general Uygur population from south and north region of Xinjiang, China.

BACKGROUND: Kaposi sarcoma (KS) is a complex multifocal neoplasm and is the major cause of death for about 50% of acquired immunodeficiency syndrome (AIDS) patients. Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus with a causal role in the development of all types of KS. KS is prevalent among the Uygur people in Xinjiang, especially in south area. Here we carried out a cross-sectional study among 1534 general Uygur individuals from south and north region of Xinjiang to assess the seroprevalence of KSHV and to identify the potential correlation between KSHV seroprevalence and KS incidence. RESULTS: Seroprevalence of KSHV in South and North Xinjiang was 23.1% and 25.9%, respectively. Older age was independently associated with higher KSHV seroprevalence. In subjects from South Xinjiang, lower educational level and reported drinking were each independently associated with higher KSHV seroprevalence. Furthermore, the antibody titer was significantly lower in both south and north KSHV seropositive individuals compared with KS patients, as analyzed by gradient dilution (P < 0.001). CONCLUSION: KSHV is highly prevalent in the general Uygur population in both South and North Xinjiang. Interestingly, the infection rate of KSHV in these two geographical areas did not correlate well with KS incidence. Perhaps unknown factors exist that promote the progression of KSHV infection to KS development in the local minority groups.

Kaposi sarcoma presenting as yellow-green penile plaques in a black man with HIV.

Kaposi sarcoma characteristically presents with violaceous papules, plaques, or nodules due to the vascular nature of the lesions. We present the case of a human immunodeficiency virus (HIV)-positive black man with yellow-green penile plaques. Biopsy results revealed leukoedema and slitlike vascular spaces. Immunohistochemistry was positive for CD31 and CD34. He was treated with highly active antiretroviral therapy (HAART) and the penile plaques improved. Localized yellow-green penile plaques are an uncommon presentation of the well-known clinical entity, Kaposi sarcoma. This case underscores the varied clinical presentations that can occur in skin of color and the importance of histopathology in the assessment of uncharacteristic clinical presentations, especially in immunosuppressed patients.

Concurrent development of HIV-negative Kaposi's sarcoma and mycosis fungoides in an elderly Inuit from Canada.

An 88-year-old Inuit man from Northern Canada presented with an extensive skin rash associated with numerous violaceous skin nodules on his palms and lower extremities. Biopsy of a skin nodule revealed Kaposi's sarcoma (KS), a human herpesvirus 8 (HHV8)-associated malignancy, whereas biopsy of the erythematous skin showed an atypical infiltrate of CD4-positive T-cells that, together with TCR gene rearrangement and presence of clonal T-cells in peripheral blood by flow cytometry, was consistent with a T-cell lymphoma, mycosis fungoides (MF) subtype. Serology was negative for HIV and HTLV-I/II and no immunodeficiency syndrome was identified. The patient was successfully treated with an oral retinoid for KS, and with topical hydrocortisone and ultraviolet B (UVB) phototherapy for MF. This case highlights the existence of HHV8-related lesions in native persons of Northern Canada, and also that MF-induced immunosuppression combined with immunosenescence may play a role in the development of non-HIV-related KS.

TP53 codon 72 polymorphism in classic, endemic and epidemic Kaposi's sarcoma in African and Caucasian patients.

OBJECTIVES: Several studies have examined the association of codon 72 polymorphism of the TP53 gene, encoding either arginine or proline, in several tumor types but none have investigated its role in Kaposi's sarcoma (KS) development. METHODS: In this prevalent case-control study, 67 cutaneous lesions of classic, iatrogenic, endemic as well as epidemic KS from African (n = 22) and Caucasian (n = 45) patients, and blood samples from 150 healthy controls (n = 57 African, n = 93 Caucasian) have been analyzed for arginine and proline allele distribution. RESULTS: Among African cases the proline homozygous, heterozygous and arginine homozygous genotype frequencies were 50.0, 31.8 and 18.2%, respectively, and among controls 54.4, 40.3, and 5.3%, respectively (p = 0.1872). Conversely, among Caucasian cases genotype distributions were 6.7, 55.6, and 37.8%, and among controls 7.5, 34.4, and 58.1%, respectively (p = 0.0567). No significant differences in arginine and proline allele distribution were observed when the cases were stratified by HIV status/tumor type. CONCLUSIONS: The results obtained in this study suggest that p53 polymorphism at codon 72 does not represent a risk factor for the development of all forms of KS, either among African or among Caucasian populations.

Increasing incidence of Kaposi's sarcoma in black South Africans in KwaZulu-Natal, South Africa (1983-2006).

The aim of the study was to describe the temporal trends in the incidence of Kaposi's sarcoma (KS) in black South Africans in KwaZulu-Natal (KZN). The study was designed as a retrospective record review. The incidence of Kaposi's sarcoma was estimated using administrative records for patients receiving care for KS through public sector oncology clinics in KZN, 1983-2006. Annual age-standardized incidence rates were calculated using provincial census data for the denominator. Age-specific rates were calculated for the pre-AIDS (1983-1989) and for the generalized AIDS epidemic eras (2006). Age-standardized incidence of KS increased in KZN from <1:100,000 in 1990 to at least 15:100,000 in 2006; this increase was observed in both men and women. There was a shift in the peak age-specific incidence rates from the sixth decade of life in the pre-AIDS era to the fourth and fifth decades in the AIDS era. In conclusion, KS is a growing public health problem in KZN, South Africa. These data reinforce the need for comprehensive national access to and roll-out of antiretroviral drugs, given their success in prevention and treatment of KS in first-world settings.

Ultraviolet Radiation and Kaposi Sarcoma Incidence in a Nationwide US Cohort of HIV-Infected Men.

Background: Although ultraviolet radiation (UVR) is established as both an inducer of herpes simplex virus reactivation and as the primary risk factor for many common skin cancers, its relationship with human herpes virus 8 (HHV8) infection or risk of Kaposi sarcoma (KS) is unknown. Methods: Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between ambient UVR, history of nonmelanoma skin cancer (NMSC; as a biomarker of personal cumulative UVR dose), and incidence of first primary KS in a nationwide US cohort of white and African American male veterans infected with HIV between 1986 and 1996 (prior to the widespread availability of treatment) using Cox regression. All statistical tests were two-sided. Results: Based on discharge records, there were 422 newly diagnosed KS cases among 17 597 HIV-infected veterans. Cohort members with prior NMSC had a statistically significantly increased risk of KS (HR = 8.64, 95% CI = 6.23 to 11.96) in the total population. Risk of KS was higher for quartile 4 vs 1 among the total population (HR = 1.49, 95% CI = 1.02 to 2.16, Ptrend UVR quartile [coded 1 to 4] = .02) and among whites (HR = 1.75, 95% CI = 1.11 to 2.78, Ptrend = .009), but not among African Americans (HR = 1.23, 95% CI = 0.71 to 2.15, Ptrend = .23). Conclusions: KS risk was elevated among HIV-infected men with NMSC diagnosis and in those living in locations with high ambient UVR at time of HIV diagnosis. Our novel findings suggesting that UVR exposure may increase KS risk warrant further investigation.

Classic Kaposi's sarcoma presenting first with gastrointestinal tract involvement in a HIV-negative Inuit male--a case report and review of the literature.

Kaposi's sarcoma (KS) is a multicentric low-grade vascular malignancy. In North America, it is usually seen in AIDS and solid organ transplant populations. Classic KS is a subtype that traditionally occurs in elderly HIV-negative males of Mediterranean, Eastern European, and Jewish descent. Patients with classic KS characteristically present with skin lesions in the distal extremities. Involvement of the viscera is uncommon in classic KS, but may occur in the late stages of the disease. We report the first case of classic KS presenting in the gastrointestinal tract of an elderly HIV-negative Inuit male from Northern Quebec, Canada.

Seroepidemiology and molecular epidemiology of Kaposi's sarcoma-associated herpesvirus among Jewish population groups in Israel.

BACKGROUND: The incidence of classic Kaposi's sarcoma among Jews in Israel is among the highest in the developed world. Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) is causally linked to Kaposi's sarcoma. Very little is known about the prevalence of KSHV in the Middle East or about the modes of transmission in Mediterranean countries. METHODS: From 1992 through 1995, sera were obtained from 1648 adults who had tested positive for hepatitis B virus (HBV) surface antigen 20 years earlier at blood donations; sera were also obtained from 2403 of their family members. All sera were tested for anti-KSHV antibodies with the use of an indirect immunofluorescence assay. To analyze the effects of various factors on the risk of KSHV infection for both the HBV-positive cohort and their families, logistic regression for cluster data and generalized estimating equations were used. All statistical tests were two-sided. RESULTS: Among family members, the seroprevalence of antibodies against KSHV was 9.9% (95% confidence interval [CI] = 8.7% to 11.1%); among the former blood donors who had tested positive for hepatitis B, it was 22% (95% CI = 19.9% to 24.1%). Overall, the best predictor of KSHV status was the place of birth. The most important risk factors found for both husband and wife to test KSHV positive were their own places of birth and their spouse's seropositivity. For a child to test positive, the most important risk factor was maternal seropositivity. CONCLUSIONS: The crude prevalence rate of KSHV among the Jewish population in Israel is 9.9%. Important routes of KSHV transmission in the families studied are spouse to spouse and mother to child. The presence of KSHV in Jews in Israel of all ethnic origins and their high incidence of reported Kaposi's sarcoma suggest that KSHV was introduced into the Jewish population prior to the major Diaspora.

Treatment of Kaposi's sarcoma after solid organ transplantation.

PURPOSE: This retrospective review of all patients who developed Kaposi's sarcoma (KS) after solid organ transplantation at a single institution was undertaken to define the clinical presentation of this malignancy in the setting of iatrogenic immunodeficiency, and to determine the most appropriate treatment for patients in this clinical setting. MATERIALS AND METHODS: The records of 2,099 patients who underwent heart, lung, liver, or kidney transplantation at The Toronto Hospital between January 1, 1981 and June 30, 1995, were reviewed. Twelve patients were identified who developed biopsy-proven KS in the posttransplantation period. Five patients who had disseminated KS who had not responded to either reduction or withdrawal of immunosuppression or to local radiotherapy were treated with combination chemotherapy consisting of doxorubicin 20 to 30 mg/m2, bleomycin 10 mg/m2, and vincristine 2 mg (ABV) administered intravenously every 3 weeks. RESULTS: Eight of 12 patients were male and nine were of Italian origin. KS was limited to a localized area of the skin for only six patients, all after kidney transplantation. Visceral KS was present in three patients. Four of five patients responded to ABV chemotherapy (two complete and two partial remissions). The fifth patient responded to second-line etoposide and cisplatin. The median duration of response was in excess of 13 months (range, 8+ to 45+ months). Toxicity was limited to grade 1 neurotoxicity and grade 1 skin toxicity. CONCLUSION: KS is an uncommon but recognized complication of solid organ transplantation. Combination chemotherapy is a safe and effective treatment for patients with disseminated or visceral KS that fails to respond to changes in immunosuppression.

Racial and ethnic variations in incidence and pattern of malignancies after kidney transplantation.

Malignancies are a well-recognized complication of renal transplantation. Although the problem is well studied in developed countries, less is known about it in developing countries. Although geographic and ethnic variations have been alluded to in several reports, to our knowledge the subject has not been investigated formally. From April 1976 through March 1999, 41 (7.6%) patients were diagnosed with cancer among a heterogeneous population of renal allograft recipients treated at our institution in Cape Town, South Africa. The incidence of malignancies was comparable in white and nonwhite patients. However, squamous cell cancer and basal cell cancer of the skin (in that order) were the most common cancers in white patients, in whom they occurred exclusively. On the other hand, Kaposi sarcoma was the most common cancer in nonwhite renal allograft recipients, in whom it accounted for almost 80% of all cancers. Review of the world literature suggests that posttransplant cancers are less common in developing countries; Kaposi sarcoma is the most common lesion, with few exceptions. Malignant lymphomas are also more common in developing countries. The impact of different immunosuppressive regimens is controversial. In general, cyclosporine is not associated with a significant increase in the incidence of cancer after renal transplantation, although the time to the first cancer may be reduced. In our experience, the pattern of posttransplant cancers in white and nonwhite patients living in the same geographic region epitomizes the world experience of the disease and suggests that genetic factors, rather than geography, are the more important determinants of cancer development after renal transplantation.

Molecular characterization of Kaposi's sarcoma associated herpesvirus (KSHV) from patients with AIDS-associated Kaposi's sarcoma in Sao Paulo, Brazil.

BACKGROUND: Kaposi's sarcoma (KS) is caused by Kaposi's sarcoma associated herpesvirus (KSHV/HHV-8), the eighth Herpesvirus found to infect humans. The molecular epidemiology of KSHV is related closely to ethnicity and geographical location of studied populations. There is little epidemiological and molecular information about KSHV strains circulating in Brazil. OBJECTIVES: To characterize KSHV strains isolated from AIDS patients with Kaposi's sarcoma (AIDS-KS) in Sao Paulo, Brazil, and to examine associations between KSHV subtypes, ethnicity and HIV risk categories. METHODS: AIDS-KS patients were recruited consecutively at the largest AIDS reference hospital in Sao Paulo. Fragments (420 bp) of the VR1 and VR2 regions of KSHV open reading frame (ORF) K1 were amplified by nested PCR and sequenced directly. RESULTS: We analysed 37 samples from 33 patients, and found subtypes A-C in 48%, 21% and 30% of patients respectively, including two patients infected with subtype A5, a first report from Brazil. Sexual orientation was associated with subtype: 12/14 (86%) patients with subtype A were male homo/bisexual, compared with 3/8 (38%) among patients infected with subtype C (P = 0.05). A higher proportion of male patients with subtype C were of Caucasian origin (7/8 (87%)), compared with 7/16 (44%) among male patients with subtype A (P = 0.08). CONCLUSIONS: This first detailed report of KSHV subtypes among AIDS-KS patients in Brazil reports the first isolation of KSHV subtype A5 in this country, and suggests KSHV strain transmission between different ethnic groups, and association of specific strains with sexual orientation.

Kaposi's sarcoma in kidney transplant recipients: a 23-year experience.

BACKGROUND: Kaposi's sarcoma (KS) is a relatively common malignancy after kidney transplantation, accounting for up to 80% of all malignancies in developing countries. AIM: To assess the frequency of KS in renal transplant recipients, and determine the impact of demographic factors, immunosuppression and treatment options. DESIGN: Retrospective study in a single centre in South Africa. METHODS: Charts and pathology reports of 542 recipients of 623 kidney allografts treated at our institution between 1976 and 1999 were reviewed. RESULTS: After a mean follow-up of 6.4 years, 21 (3.9%) recipients had KS, representing 47.7% of all post-transplant malignancies. KS accounted for more post-transplant cancers in non-White than White patients (79.1% vs. 11.7%, p < 0.001). KS was equally common in males and females, and was not more frequent under cyclosporine. Skin involvement was universal; visceral disease occurred in six patients (28.6%). Sixteen (94.1%) patients with limited skin disease and two (100%) with superficial nodal disease responded to withdrawal or reduction of immunosuppression. Renal function was preserved when immunosuppression was reduced instead of withdrawn (p = 0.02). Patients with vital organ involvement succumbed rapidly to KS. Post-mortem examination revealed more extensive disease than was suspected clinically. DISCUSSION: Ethnic differences exist in the frequency of KS in patients residing in the same geographical area. Since withdrawal results in graft loss, reducing immunosuppression should be first-line treatment for patients with disease limited to skin, and possibly for disease of the superficial lymph nodes. The malignant behaviour of KS, and extent of pathological involvement, cast doubt on the idea that KS is a hyperplasia rather than a true malignancy.

Classic Kaposi's sarcoma in the Inuit of northern Quebec.

BACKGROUND: Classic Kaposi's sarcoma (KS) is predominantly a disease of eastern Mediterranean and Ashkenazi Jewish elderly men. Nevertheless, the disease has been reported to occur in people from various other ethnic and regional backgrounds. OBJECTIVE: We report, for the first time, the occurrence of classic KS in five Inuit people living in northern Quebec, Canada. METHODS AND RESULTS: We describe the case of a 69-year-old Inuit man with classic KS, and report four other cases of KS in the Inuit population, identified by a review of our hospital's dermatopathology records. CONCLUSION: The discovery of classic KS in the Inuit population of northern Quebec brings with it new questions as to the origins of the KS-associated herpes virus in this population. It is our belief that the answers to these questions are in the genotype of the virus that is present in this community.