Dear Sir, Papillomaviruses (PVs) are nonenveloped DNA viruses that are tumorigenic to humans and numerous animal species. 1 Human PVs (HPVs) are of great medical importance because high-risk HPV types, primarily , are the causative agents of cancer. The most important and best documented HPV-associated cancer is cervical carcinoma, with which HPV is associated in more than 90% of cases. [2][3][4] Much of our understanding of PVs, their life cycle and other relevant aspects of pathogenesis has derived from studies of animal PVs as early as the beginning of last century. Bovine PV (BPV), cotton-tail rabbit PV and canine oral PV have been extensively studied and all have contributed to the elucidation of PV pathogenesis. 5 Although these three systems have been exceedingly useful models in understanding the oncogenic potential of the virus, the relationship between virus and cofactors, and the development of antiviral vaccines, the explosion of research on HPV and, more recently, the availability of the anti-HPV prophylactic vaccines have generated the widespread belief that PV research is on the wane and animal models are no more needed. In this letter we will argue that this is not the case and that animal PVs still provide new avenues of research. Although this is so for all animal PVs aforementioned, we will focus specifically on new facets of BPV infection and pathogenesis which have come to light, or have been confirmed recently in bovids and equids. 6,7 These are as follows: the association of BPV with lymphoepithelial, vascular and other mesenchymal tumors in cattle 8 ; cross-species infection by BPV in equids with induction of sarcoids, 7 and in buffalo and bison with induction of warts 9,10 ; elucidation of the molecular mechanisms of the oncoprotein E5 in vivo 11,12 ; the presence and expression of BPV DNA in blood cells of both cattle and horses and its possible role in virus transmission and spreading 13,14 ; and the association of BPV and inflammation. 15 Do these observations point to new opportunities in HPV research? Although BPV infection of species other than Bos is the only documented instance of natural cross-species infection, it is unlikely that this is a single occurrence and anecdotal or single reports of BPV infection in humans handling infected cattle, or of HPV infection in domestic animals, should be investigated.Can HPV infect nonepithelial tissues? Approximately a decade ago, the first reports of the presence of HPV DNA in blood cells of patients proved controversial; the now accepted presence of BPV DNA and of BPV E5 protein in blood cells of cattle and horses should stimulate new interest in similar investigations in humans, especially concerning the role of viral sequences in blood cells. Additionally, a recent article confirmed that, like BPV, HPV can infect vascular tissue, 16 and these studies should be expanded to confirm the generality of this observation.The importance of chronic inflammation in oncogenesis is a subject of intense investigation. Although the infectious cycle ...