KSHV K15 genetic heterogeneity is associated with Kaposi sarcoma aggressiveness through modulation of the host inflammatory microenvironment.

KSHV K15 M-genotype is linked to increased Kaposi sarcoma severity through heightened inflammation and edema, independent of host immunodeficiency.

• Why it matters: Current risk assessments for KS rely on anatomical staging that does not fully capture biological variability, limiting personalized treatment strategies.
• What they did: The study analyzed 156 patients, identifying K15 genotypes and their association with clinical features, inflammation markers, and disease progression using causal mediation and LASSO regression models.
• The result: Findings show the K15 M-genotype correlates with a hyper-inflammatory state and severe edema, enabling a prognostic model that outperforms traditional staging and supports biology-driven management of high-risk patients.