There are conflicting reports that integration of the wild-type adeno-associated virus 2 (AAV2) genome is associated with induction of hepatocellular carcinoma (HCC) in a small subset of patients. However, there are several lines of evidence that contradict this assertion: (i) AAV2 has long been known to be a non-pathogenic virus, although ∼90% of the human population is seropositive for AAV2 antibodies; (ii) AAV2 has been shown to possess anticancer activity; (iii) epidemiological evidence suggests that AAV2 infection plays a protective role against cervical carcinoma; and (iv) five different AAV serotype vectors (AAV1, AAV2, AAV5, AAV8, and AAV9) have been or are currently being used in 162 Phase I/II clinical trials and one Phase III clinical trial in humans to date, and no cancer of any type has ever been observed or reported. A brief historical account of the putative role of infection by AAV in the etiology of cancer, or lack thereof, is presented.
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