Abstract

CPV1 (also called COPV) is a papillomavirus responsible for oral papillomatosis in young dogs. The involvement of this viral type in oral oncogenesis has been hypothesized in oral squamous cell carcinomas (SCCs), but has never been investigated in other neoplastic and hyperplastic oral lesions of dogs. Aim of this study was to investigate the presence of CPV1 in different neoplastic and hyperplastic lesions in order to assess its role in canine oral oncogenesis; according to the results obtained, a second aim of the study was to define if the dog can be considered a valid animal model for oral high risk HPV-induced tumors. Eighty-eight formalin-fixed, paraffin-embedded (FFPE) canine oral lesions including 78 oral tumors (papillomas, SCCs, melanomas, ameloblastomas, oral adenocarcinomas) and 10 hyperplastic lesions (gingival hyperplasia) were investigated with immunohistochemistry for the presence of papillomavirus L1 protein and with Real-Time PCR for CPV1 DNA. RT-PCR for RNA was performed on selected samples. All viral papillomas tested were positive for immunohistochemistry and Real-time PCR. In 3/33 (10%) SCCs, viral DNA was demonstrated but no viral RNA could be found. No positivity was observed both with immunohistochemistry and Real-Time PCR in the other hyperplastic and neoplastic lesions of the oral cavity of dogs. Even though the finding of CPV1 DNA in few SCCs in face of a negative immunohistochemistry could support the hypothesis of an abortive infection in the development of these lesions, the absence of viral RNA points out that CPV1 more likely represents an innocent bystander in SCC oncogenesis. The study demonstrates a strong association between CPV1 and oral viral papillomas whereas viral contribution to the pathogenesis of other oral lesions seems unlikely. Moreover, it suggests that a canine model of CPV1 infection for HPV-induced oncogenesis could be inappropriate.

Highlights

  • Papillomaviruses (PVs) are a group of viruses belonging to the Papillomaviridae family that are highly species-specific that can affect mammals, birds and reptiles [1]

  • The present study evaluated the presence of Canine Papillomavirus 1 (CPV1) in different hyperplastic/neoplastic canine oral lesions, in order to investigate the role of this virus in oral oncogenesis

  • The oncogenetic role of high-risk HPVs has been demonstrated for cervical cancer [16] and more awareness is growing for their role in the pathogenesis of head and neck squamous cell carcinomas (SCCs) [15]

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Summary

Introduction

Papillomaviruses (PVs) are a group of viruses belonging to the Papillomaviridae family that are highly species-specific that can affect mammals, birds and reptiles [1]. CPV1 is typically related to benign and spontaneously regressing papillomas, this viral type has been occasionally reported in non-regressing lesions, in oral and perioral squamous cell carcinomas [21], [22]. Assessing viral prevalence in oral neoplastic events in dogs could provide important insights on the potential role of this specific viral type in canine oral oncogenesis and on the usefulness of the canine model for oral HPV-induced oncogenesis in human beings. This investigation was performed on tumors of epithelial origin, such as squamous cell carcinomas, ameloblastomas and oral adenocarcinomas. Our study focused on the role of CPV1 in oral oncogenesis through the retrospective immunohistochemical and molecular analysis of a wide range of neoplastic and non-neoplastic oral lesions

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