Abstract

Papillomavirus (PV) mainly infects the squamous epithelium and may potentially lead to benign or even malignant cutaneous lesions. However, the malignant transforming ability has been identified in several types of PVs. In humans, papillomavirus (HPV) type 16 and 18 are the most prevalent causative agents of cervical cancer. Therefore, vaccines are being developed to protect against these types. For dogs, there have been limited investigations into the association of different canine papillomavirus (CPV) genotypes with malignant lesions. Understanding the high-risk CPV genotype(s) responsible for these malignant lesions would contribute to the development of interventions for preventing CPV-induced carcinomas. In the present study, a retrospective cohort of 102 pathologically confirmed papillomas and 212 squamous cell carcinomas (SCCs) were included. The viral genome and antigens in the formalin-fixed paraffin-embedded (FFPE) tissues were detected using PCR targeting pan PV E1 and COPV L1 genes and by immunohistochemistry staining (IHC), respectively. PVs were successfully detected from 11 FFPE cutaneous tissues and four oral tissues using pan PV E1- and COPV L1-based PCR, respectively. After sequencing, CPV 1, CPV 2, and CPV 6 were detected in the benign lesions using PCR and were confirmed through IHC. While CPV 9 and CPV 15 were first detected in the SCCs of dogs, CPV 16 was most often detected in SCC specimens. The association and confirmative demonstration of viral genes and intralesional antigens of CPV 9, CPV 15, and CPV 16 in SCCs highlight the potential risk of these genotypes of CPVs in malignant transformation.

Highlights

  • Papillomavirus (PV) can infect and propagate in the cutaneous and mucosal epithelial cells of a wide variety of animal species with a high species specificity [1,2,3]

  • We aimed to retrospectively identify the viral DNA of canine papillomavirus (CPV) by using the common general primers targeting the E1 and L1 from the formalin-fixed paraffin-embedded (FFPE) tissues that were diagnosed as squamous cell carcinomas (SCCs) or papillomas

  • A total of 314 FFPE tissues collected from dogs were used in this study, including 212 cases of canine SCCs and 102 cases of canine papilloma (CP)

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Summary

Introduction

Papillomavirus (PV) can infect and propagate in the cutaneous and mucosal epithelial cells of a wide variety of animal species with a high species specificity [1,2,3]. Three bovine papillomaviruses (BPV 1, BPV 2, and BPV 13) have been demonstrated to cross-infect the cutaneous fibroblastic cells in equines [4,5], the majority of PVs only infect the epithelium and cause associated lesions [3,6]. Most types of PVs cause benign proliferating skin lesions, such. Certain types of the PVs have been confirmed as risk factors of malignant skin lesions [6]. The bovine papillomavirus (BPV) types 1, 2, 4, and 13, and feline papillomavirus (FcaPV) types 2 and 3 have recently been demonstrated to be highly correlated to malignant neoplasms, such as squamous cell carcinoma (SCC), bowenoid in situ carcinoma (BISC)

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