We found that in Uganda, where KSHV is highly endemic, KSHV seropositivity was inversely associated with high factor scores on the Socioeconomic and Knowledge PCs, but not with Sexual behavioral PC. The association remained significant when we adjusted for sex, age, and geographical regions, which were considered confounders of KSHV seropositivity in this population , suggesting that the findings may be valid.
Our study results are generally consistent with previous studies, which have suggested role of socioeconomic status in KSHV seropositivity in Uganda, based on a study which also used a factor analysis approach . In that study, KSHV seropositivity was inversely associated with low factor scores of maternal and environmental factors, which are surrogates for socioeconomic status. However, that study was based on hospital-based population and relatively limited number of covariates that was available for adjustment. Our results, from a much larger population-based sample that is geographically representative of the Ugandan population, confirm the role of socioeconomic status in KSHV seropositivity in Uganda. The null association with the Sexual behavioral PC does not support an important role of sexual behavior on KSHV seropostivity in the general population in Uganda. This conclusion is different from the one reached by Shebl et al.  Although KSHV seropositivity was not associated with HIV or HSV2 infections, with lifetime number of sexual partners, having at least one sexually transmitted disease were unrelated to KSHV seropositivity, it was inversely associated with ever use of condom use and positively associated with being married and with each additional child born, suggested a possible, albeit, small role of sexual transmission. Our study found a marginal association between the Sexual behavior PC and KSHV seropositivity in crude analyses, but the association disappeared after adjusting for the other PCs, suggesting that the association detected with sexual variables may be due to confounding by other poorly understood socioeconomic factors.
While our results should not be interpreted as proving the lack of KSHV transmission via sexual contact, they support conclusions reached in other studies that that sexual transmission of KSHV is not a major source of infection in the general population [20, 25, 26]. KSHV seropositivity varies substantially by geography at a global as well local level. For example, de Sanjose and colleagues  observed significant variation in KSHV seroprevalence from 3.8% in Spain to 46% in Nigeria among women participating in a large international study conducted by the International Agency for Research on Cancer. KSHV seropositivity is lower in wealthier countries in Africa, such as South Africa, and higher in poorer countries, such as Uganda [25–27]. Within countries, KSHV seropositivity is higher in rural areas but lower in urban areas [28, 29]. The biological basis of this variation is presently unclear to us. Our results suggest that variation in socioeconomic status may play a role in the geographical variation of KSHV seropositivity [14, 26, 28]. We previously hypothesized that infection with stool parasites, which is highly prevalent in poor countries, may play a role in KSHV transmission [30, 31]. Findings by Lin et al. that KS patients attending the Uganda Cancer Institute were more likely to have a higher carriage of Strongyloides parasites than patients with other cancers treated at the same hospital  provide some support for the hypothesis. The hypothesis was also supported by a study of mother-infant pairs in Uganda , which reported that detection of malaria parasitaemia, hookworm and Mansonella perstans in stool was associated KSHV seropositivity. However, KSHV was not associated with some other parasites evaluated in the same study, including Schistosoma mansoni, Strongyloides stercoralis, Trichuris trichiura, Ascaris lumbricoides and Trichostrongylus species, suggesting that the role of parasites in the geographical variation of KSHV seropositivity requires further evaluation.
Strengths and limitations
The strengths of our study include having detailed data on a nationally representative sample, which enabled us to use PCA methods to evaluate associations with KSHV seropositivity. Exclusion of variables where prior studies indicated significant associations enabled us to confirm those previous associations after taking into account all available data. PCA has the ability to identify independent factors that explain the maximum amount of mutual correlation . However, our findings should be interpreted with caution. First, while the PCA methods offer a parsimonious way to transform many correlated variables into a few uncorrelated variables, it may mask relevant associations. For instance, some sexual behavioral variables such as ever used condom from the last sex intercourse or number of children born were found to be associated with KSHV seropositivity , but PCA does not reveal this association. Moreover, since PCA is summing up across errors in data collection, data entry and laboratory testing, some contradictory patterns can be found compared to previous findings. Second, our data are cross-sectional; therefore, it is not possible to determine the direction of causality. Third, KSHV serology is imperfect , thus, misclassification of results, although it would be random, is possible.