Fluke-borne viruses are a risk factor and diagnostic target for diseases caused by carcinogenic trematodes

Three trematode parasites, Schistosoma haematobium, Opisthorchis viverrini, and Clonorchis sinensis are recognized group 1 carcinogens for their roles in squamous cell carcinoma of the urinary bladder and bile duct cancer (cholangiocarcinoma). We aimed to assess the presence of fluke viruses and their association with malignancy in fluke infections. We showed that all three carcinogenic trematodes harbored related viruses. Focusing on O. viverrini, we observed virus persistence at discrete life stages and viral tropism for the fluke tegument, and we provided molecular and serological evidence of parasitized hosts exposure to viral RNA and proteins. Serological analyses confirmed seroconversion of residents in endemic sites and revealed that antibody titers and avidity against fluke-borne viruses increase in individuals with hepatobiliary diseases. Random forest models discriminated efficiently between liver-fluke-infected participants without disease and those with periductal fibrosis or cholangiocarcinoma. Thus, we show that fluke-borne viruses are risk factors and diagnostic targets for fluke-associated cancer.