Jalilvand et al. Infectious Agents and Cancer 2011, 6:5 http://www.infectagentscancer.com/content/6/1/5 REVIEW Open Access Seroprevalence of Human herpesvirus 8 (HHV-8) and incidence of Kaposi’s sarcoma in Iran Somayeh Jalilvand1, Zabihollah Shoja1, Talat Mokhtari-Azad1, Rakhshandeh Nategh1 and Ahmad Gharehbaghian2* Abstract Seroepidemiological surveys show that the prevalence of human herpesvirus 8 (HHV-8) infection mostly varies in various geographical areas and reflects the local incidence of classic and endemic KS, being widespread in sub- Saharan Africa and Mediterranean countries and uncommon in the USA and Northern Europe. In the Middle East only few populations, such as Ashkenazi and Sephardic groups in Israel, have been adequately evaluated for HHV-8 seroprevalence. Among Iranian population a striking higher seroprevalence of HHV8 has been reported among haemodialysis (16.9%), renal transplant recipients (25%) and HIV (45.7%) patients compared to blood donors (2%). Kaposi’s sarcoma (KS) is the rarest cancer in Iran, with an annual age-standardized incidence varying from 0.10 to 0.17 per 100,000 in males and from 0.06 to 0.08 per 100,000 in females. KS, however, is one of the most important malignancies in Iranian renal transplanted patients affecting up to 2.4% of organ recipients. The epidemiology of HHV8 and KS in Iran needs further evaluation. While the high prevalence of HHV-8 antibodies in HIV positive and haemodialysis individuals may be attributed to high-risk sexual behavior and polytransfusions, respectively, unknown determinants may be responsible for high seroprevalence of HHV8 and high incidence of KS in solid organ recipients. A global survey on HHV8 seroprevalence in Iran is mandatory to define co-factors associated with HHV8 infection and KS risk in the general Iranian population and in specific patient groups. Introduction lymphoma [17] as well as multicentric Castelman’sdis- Kaposi’s sarcoma (KS) is a mesenchymal tumor invol- ease [16,18]. ving blood and lymphatic vessels that was first described Seroepidemiological surveys have shown that HHV-8 in Eastern Europe in the late 19th century [1] and classi- infection is not ubiquitous [19]. The virus is less preva- cally considered an indolent disease of elderly men. Now lent in northern Europe, North America, and most of days, Kaposi’s sarcoma has been classified in four differ- Asia, and is more frequent in the Mediterranean area ent clinical and epidemiological forms [2]: 1) Classic KS, and parts of South America, and highly prevalent in mainly occurring in elderly men of Mediterranean or sub-Saharan Africa [20-23]. Several studies have been Eastern European origin [3-6]; 2) African-endemic KS performed in some Middle Eastern countries. In Israel [6-9]; 3) Iatrogenic KS, developing in solid organ trans- seropositivity of HHV-8 has been ranging from 8.4% to plantation recipients [6,10-12] and 4) Epidemic or 22% in healthy individuals [24,25]. In Saudi Arabia sero- AIDS-associated KS [6,13-15] prevalence of HHV-8 was reported at 1.7% and 18% in In 1994 Chang et al. identified fragments of the Kapo- healthy subjects and renal transplant recipients, respec- si’s sarcoma-associated herpesvirus (KSHV) genome in tively [26]. epidemic KS tissues, subsequently called human herpes- Few studies have been performed on the HHV-8 dis- virus type 8 (HHV-8) [16]. HHV-8 is considered to be tribution and incidence of Kaposi’s sarcoma in Iran. the etiological agent of all forms of Kaposi’ssarcoma This study aimed to recapitulate available data on the [2], and has been consistently associated with two types seroepidemiology of HHV-8 and incidence of KS in the of lymphoproliferative disease, namely body cavity-based Iranian population. A systematic review of the published articles from January 1980 to December 2010 was con- ducted to assess the seroprevalence of HHV-8 and the * Correspondence: [email protected] incidence of KS in Iran. Data were identified by searches 2Research Center of Iranian Blood Transfusion Organization, Tehran, Iran Full list of author information is available at the end of the article of Medline, Current Contents, PubMed, and references © 2011 Jalilvand et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Jalilvand et al. Infectious Agents and Cancer 2011, 6:5 Page 2 of 6 http://www.infectagentscancer.com/content/6/1/5 from relevant articles, with the search terms “Kaposi’s Iran [34-36]. About 1.14-6% (mean = 2.8%) of Iranian sarcoma” or “HHV-8”, and “Iran”. renal transplant recipients develop cancer lesions, mostly skin cancers (Table 1) [37-43]. These findings Epidemiology of classic Kaposi’s sarcoma in Iran are consistent with other report in Middle Eastern coun- Data from the National Cancer Registry of Iran have tries. The prevalence of all malignancies in renal trans- reported that KS is the rarest cancer among Iranians plant recipients was 1.9% in Pakistan [44], 4% in Turkey [27]. Only 50, 44, and 61 KS cases were reported in the [45], 6.8% in Saudi Arabia [46], 4.8% in Kuwait [47], National Cancer Registry in 2004 [27,28], 2005 [27] and 5.9% in Iraq [48], and 1.7% in Jordan [49]. 2006 [27,28] respectively, and 101 new cases have been KS is one of the most common cancers after renal registered in Tehran Population Based Cancer Registry transplantation in Iran [36] representing 28.5-70% from 1998-2002 [27,29]. The annual age-standardized (mean = 42.2%) of all post-transplant malignancies incidence rate was reported to be from 0.10 to 0.17 per (Table 1) [37-43]. Other reports from the Middle East- 100,000 in males and from 0.06 to 0.08 per 100,000 in ern region showed that KS was the most common post- females [27]. Peak incidence has been reported at ages transplantation malignancy with frequencies of 25% [45] of 50-79 years. The male/female ratio in different and 68% in Turkey [50], 44% in Pakistan [51], and 50% reports varies from 3.2:1 to 1.8:1 and the elderly might in Iraq [48]. be a common associated factor for KS [27]. There were In Iran, incidence of KS among renal transplants var- no published reports about AIDS-KS in Iran. ied from 0.45% to 2.4% in different studies (Table 1) Worldwide KS accounts for only 0.02% to 0.07% of all [37,38,40-43,52-55]. In other countries of this region, malignancies in the general population [30]. The regions the figures were 0.55% in Jordan [49], 3.2% in Turkey with the highest incidence are Africa, where KS repre- [56] and 4.9% in Saudi Arabia [46]. The incidence of KS sents 3% to 9% of all cancer cases [31], Mediterranean was 0.7% [56], 1.7% [57] and 3.9% [58] among renal and Eastern European areas, with specific geographic transplant recipients in Taiwan, Greece and South foci in Italy, Greece, and Israel [4,5]. Africa, respectively. Therefore, the incidence of KS fol- lowing kidney transplantation varies significantly in dif- Epidemiology of post-transplant Kaposi’s sarcoma in Iran ferent geographic areas [59], and this is supporting the The incidence of KS in kidney recipients has increased theory of ethnic or environmental factors in its patho- following an enormous increase in the number of kidney genesis. Globally, KS is most often seen in transplant transplantations during the recent decades, particularly recipients of Mediterranean, Jewish, Arabic, Caribbean, of those of Mediterranean descent [32]. Post-transplan- or African descent and the reported incidence ranges tation KS develops in 23% to 28% of HHV8 seropositive from 0.5% in most Western countries (including the patients and in only 0.7% of seronegative patients United States) up to 5.3% in Saudi Arabia [32]. [32-34]. The KS incidence among Iranian transplants recipients The rate of chronic kidney disease and renal trans- had a peak during the first 2 years post transplantation. plantations has increased during the last two decades in The time interval between transplantation and onset of Table 1 List of published data on the incidence of Kaposi’s sarcoma in renal transplanted patients in Iran City Renal Male/ Post-transplant KS Male/ Cutaneous/ Study period References Transplants Female (N) Malignancies (%) cases Female visceral (N) (%) (N) Tehran 681 438/243 - 5 (0.73) 3/2 - 2000-2002 [52] Tehran 100 53/47 6 (6) 2 (2.0) 2/0 - 2000-2002 [39] Tehran 2211 - - 10 (0.45) 8/2 8/2 1984-2007 [53] Tehran 1750 - 28 (1.6) 13 (0.74) - - 1984-1999 [42] Tehran 2050 - - 18 (0.87) 13/5 18/1 1984-1999 [54] Ahwaz 580 330/250 20 (3.4) 14 (2.4) 11/3 11/3 - [40] Babol 380 - 12 (3.15) 5 (1.3) - - 1999-2005 [41] Shiraz 892 537/355 21 (2.3) 6 (0.68) 5/1 4/2 1988-2001 [38] Tehran, Urmia, Babol, Sari, 7,939 5018/2921 162 (2.04) 55 (0.69) 33/22 48/7 1984-2007 [37] Tabriz, Hormozgan, Kerman Tehran, Urmia, Babol, Sari, 11,255 7109/4146 128 (1.14) 77 (0.68) 48/29 - 1984-2008 [43] Tabriz, Hormozgan, Kerman, Isfahan, Ahwaz Jalilvand et al. Infectious Agents and Cancer 2011, 6:5 Page 3 of 6 http://www.infectagentscancer.com/content/6/1/5 KS was relatively early compared to other skin tumors. tested for the presence of antibodies against HHV-8 This observation is in agreement with other studies lytic antigens by HHV-8 IgG EIA and by HHV-8 IgG from the Middle East region reporting appearance of KS IFA commercial kits (Biotrin, Ireland) as for manufac- lesions in 6.5 to 27 months following kidney transplan- turer’s instructions and each sample defined as “posi- tation [26].