Absence of tissue evidence for Kaposi sarcoma-associated herpesvirus in osteosarcomna from a KSHV-endemic African setting

Abstract

Osteosarcoma (OS) is a rare primary bone malignancy, though it represents the most frequently diagnosed primary bone tumor among children and young adults. Following the report linking OS and Kaposi sarcoma (KS)-associated herpesvirus (KSHV) infection in Xinjiang China, we investigated whether KSHV is detected in OS tumor tissues in sub-Saharan Africa, a region endemic to KSHV. We analyzed 30 OS specimens, comprising 23 retrospectively collected archival formalin-fixed paraffin specimens and 7 prospectively collected frozen specimens between 2021 and 2026 in Tanzania. KSHV-LANA protein expression was examined by immunohistochemistry (IHC) in all 30 specimens. KSHV-ORF26 and -LANA DNA were assessed by PCR in the 7 prospectively collected specimens that met predefined DNA-quality criteria. Thirty OS tissues were evaluated, and the median age was 23 years. Jaw was the most frequent single anatomical site biopsied. While all 30 OS tissues tested positive for the cellular proliferation marker Ki-67 by IHC, none of these tissues had detectable KSHV LANA expression. Among the seven fresh-frozen OS specimens tested by PCR, none demonstrated detectable KSHV-ORF26 or -LANA DNA. KSHV DNA was detected in the control KS tissues only. In this OS cohort, KSHV LANA protein was not detected in any of the 30 OS specimens examined by IHC and KSHV-ORF26 or -LANA DNA was not detected in the seven molecularly evaluable fresh-frozen tumors. Overall, these findings do not support a high-frequency KSHV–OS association comparable to that reported in Xinjiang. Larger studies with appropriately preserved specimens are required to exclude possible lower-frequency associations and confirm whether contrasting associations are geographically, ethnically, or genetically linked.