Abstract
IntroductionKaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is important both in transmission of HHV-8 and progression to KS. We characterized the sites and frequency of HHV-8 detection in Ugandans with and without HIV and KS.MethodsParticipants were enrolled into one of four groups on the basis of HIV and KS status (HIV negative/KS negative, HIV positive/KS negative, HIV negative/KS positive, and HIV positive/KS positive). Participants collected oral swabs daily and clinicians collected oral swabs, anogenital swabs, and plasma samples weekly over 4 weeks. HHV-8 DNA at each site was quantified by polymerase chain reaction (PCR).Results78 participants collected a total of 2063 orals swabs and 358 plasma samples. Of these, 428 (21%) oral swabs and 96 (27%) plasma samples had detectable HHV-8 DNA. HHV-8 was detected more frequently in both the oropharynx of persons with KS (24 (57%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p = 0.002) and the peripheral blood (30 (71%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p<0.001). In a multivariate model, HHV-8 viremia was more frequent among men (IRR = 3.3, 95% CI = 1.7–6.2, p<0.001), persons with KS (IRR = 3.9, 95% CI = 1.7–9.0, p = 0.001) and persons with HIV infection (IRR = 1.7, 95% CI = 1.0–2.7, p = 0.03). Importantly, oral HHV-8 detection predicted the subsequent HHV-8 viremia. HHV-8 viremia was significantly more common when HHV-8 DNA was detected from the oropharynx during the week prior than when oral HHV-8 was not detected (RR = 3.3, 95% CI = 1.8–5.9 p<0.001). Genital HHV-8 detection was rare (9 (3%) of 272 swabs).ConclusionsHHV-8 detection is frequent in the oropharynx and peripheral blood of Ugandans with endemic and epidemic KS. Replication at these sites is highly correlated, and viremia is increased in men and those with HIV. The high incidence of HHV-8 replication at multiple anatomic sites may be an important factor leading to and sustaining the high prevalence of KS in Uganda.
Highlights
Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV
Study participants Eighty-seven participants were enrolled in the study: one participant did not have histological confirmation of KS, and another participant enrolled but was lost to follow up before collecting any oral swabs: these participants were excluded from further analyses (Figure 1)
6 (46%) of 13 Human herpesvirus-8 (HHV-8) seronegative persons had clinical or virologic evidence of HHV-8 infection and had false negative HHV-8 serologies (3 persons had HHV-8 detected from $1 mucosal samples and biopsy proven KS, 1 had biopsy proven KS only, 2 had HHV-8 detected from mucosal samples on $1 occasion); these participants were included in the analyses
Summary
Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) is the causative agent of all forms of KS [5,6], and infection is endemic in Uganda, with an estimated seroprevalence between 36% and 60% [7,8,9,10]. Despite this high seroprevalence, both endemic and epidemic KS occur in a minority of persons who are HHV-8 infected, and little is known about the underlying mechanisms determining the transition from asymptomatic HHV-8 infection to KS disease. Oral epithelial cells had detectable HHV-8 mRNA and DNA [11], and HHV-8 DNA in saliva was protected from digestion with DNase, consistent with the presence of virions [14]
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