But the prevalence of EBV in HRS cells varies according to the histological subtype and epidemiologic factors from highest frequency in MCCHL to the lowest in NSCHL, and EBV-encoded LMP1 utilizes the PI3K/AKT/mTOR signaling axis to induce ectopic CD137 expression in HRS cells, which results in enhancing the proliferation rate of HRS cells [294, 295]. Here, PIK3CA is linked to nodular sclerosis classical Hodgkin lymphoma.