Molecular Detection of Epstein - Barr virus in Nasopharyngeal Carcinoma among Sudanese population

Nasopharyngeal carcinoma (NPC) is relatively a rare cancer in most parts of the world, although, it is the most commonly diagnosed head and neck cancer in certain region of Southeast Asia. Evolving body of researches indicates that the age standardized incidence rate is less than 1 per 100.000 people per year for either gender worldwide [15, 16]. Isolated northern populations such as Eskimos and Greenlanders also show high incidence. There is a moderate incidence in North Africa, Israel, Kuwait, the Sudan and parts of Kenya and Uganda. Furthermore, in most populations, the age standardized annual incidence rate of NPC is much higher among males compared to females, with male to female ratio around 2–3: 1 in high and moderate risk areas.

Infection with EBV has been implicated in the development of nasopharyngeal carcinoma by several different lines of compelling evidence. Historically, the first indication was the observation that sera from African and American patients with nasopharyngeal carcinoma were often more positive for precipitating antibodies to antigens prepared from cultured Burkitt lymphoma cells than controls [17]. This observation has since been confirmed in serological studies showing elevated titers of IgG and in particular IgA antibodies against EBV viral capsid, early and nuclear antigens in nasopharyngeal carcinoma patients data being less convincing for type I than types II and III, manifesting as apparent ethnic variations [18]. Much compelling than the sero-prevalence surveys in patients are, the results of a prospective study of 9699 persons which showed that presence of IgA anti-EBV viral capsid antigen antibodies or neutralizing EBV specific anti-DNase antibodies correlated with subsequent risk for nasopharyngeal carcinoma [19].

In the current study, the correlation between NPC and the presence of the EBV genome was evaluated. An extremely significant positive correlation was found based on two genes encoding for EBV viral proteins. Exhaustive studies have investigated this correlation; nevertheless, these findings are greatly contradictory. The role of EBV infection in the etiology of NPC in Sudan had been reported since 1979 [20]. In addition, a recent study used 53 biopsies obtained from Sudanese patients 43 with NPC beside ten normal samples were used to investigate the presence of viral genome in non malignant cells; the study was aimed at investigating the presence of EBV using EBER-ISH. Intriguingly, their results showed that all nasopharyngeal carcinoma biopsies (100%) were positive for EBER1among all carcinoma cells, however, no hybridization was observed among all 10 nonmalignant tissues [21]. Surprisingly, these are findings greatly discordant from the prevalence of EBV obtained in our present study (62.2%), possibly this might be attributed to their small sample size 43 compared to ours which is 82 specimens. Furthermore, a study was conducted by Ahmed and associates [9], on 150 biopsies obtained from Sudanese patients with NPC, was screened for the presence of EBV genes; EBV nuclear antigen-4 (EBNA-4) and latent membrane protein-1 (LMP1) using Polymerase Chain Reaction (PCR) [25]. Significantly, EBV genes were detected in 92/150 (61.3%) tissue samples, accordingly, these results are in agreement with our prevalence (62.2%). Interestingly, the incidence of EBV among South Africa patients with NPC were much higher, in a study conducted by Janse and his associates, they investigated the incidence of EBV among 38 NPC Patients using PCR to amplified EBER region, their results shows that EBV were detected in 82% (31/38) of the tumours [21].

The distribution of NPC by gender, Among 82 NPC cases, there were 55 (67.1%), males and there were 27 (32.9%) females with male/female ratio 2.03 to 1.00, this indicating that the number of males with NPC was much higher than females, growing body of researches have previously reported this finding [7, 8, 21].

Strangely enough, the frequency of EBV infection was higher among males, however, when comparing the per centage of EBV infection within each group, (66.7%) of women were relatively infected whereas (64.7%) were men. Moreover, meaningful evidences have shown that NPC is much often diagnosed among men compared to women, interestingly, it tends to occur at an earlier age than do most cancers [22–25]. However, there are no studies, specifically, focusing on the prognostic impact of gender on NPC. Moreover the EBV positive cases were reported to be occurring between 2^th and 4^th decades of life, followed by 4^th to 6^thand 6^th to 8^th decades of life, our results in are in consistent manner resembling previous reports [9].

Regarding the histopathological subtypes of NPC among our current study populations, we found them to be WHO type II and III, whereupon in accordance to report from other endemic areas [26]. Additionally, our results are in accord with previous studies reported in Sudan [8]. Interestingly, these subtypes i.e. II and III are associated with high rates of EBV detection [27].

In regard to the distribution of EBV infection by residence and, the great majority of infections were detected among Western region’s populations, representing 15/ 51 (29.4%) followed by fully-fledged Southern region’s populations, constituting 12/51 (23.5%), these finding are in concordance to that recently reported by Ahmed and colleagues [9], which show a high incidence of EBV among western region’s populations. Additionally, a groundbreaking study conducted by Abdullah and his fellows, reported a high frequency of NPC in western Sudan, however, they attributed their data to the presence of radioactive uranium in areas [8].