Malignant Transformation of a Canine Papillomavirus Type 1-Induced Persistent Oral Papilloma in a 3-Year-Old Dog

Abstract

This case report describes a rare case of a persistent canine papillomavirus type 1 (CPV-1)-induced oral papilloma that underwent malignant transformation into an oral squamous cell carcinoma (OSCC) in a 3-year-old Labrador retriever cross. Initially, the patient had multiple and multifocal verrucous lesions populating the oral cavity exclusively. The papillomas persisted despite multiple surgical ablations, azithromycin, interferon α-2b, alternative medicines, and off-label drug use of an immunostimulant. After 1 year and 6 months, an aggressive lesion developed at the level of the left mandibular first molar (309) and progressed to a well-differentiated invasive OSCC. The presence of CPV-1 DNA in the OSCC, and the known oncogenic abilities of CPV-1, suggests that this virus might have played a significant role in the emergence of the OSCC that ultimately led to the patient's euthanasia due to poor quality of life. This is the first well-documented case where OSCC has developed from an oral papilloma caused by CPV-1 in which the presence of coinfection by another papillomavirus was excluded by multiple polymerase chain reaction tests using various primers.

The Detection and Association of Canine Papillomavirus with Benign and Malignant Skin Lesions in Dogs

“…Several retrospective studies based on molecular or serological survey evidence have declared that CPV 1 is unlikely to bring about malignant changes [49][50][51]. Controversially, accumulative studies have revealed the identification of CPV 1 in SCCs [26,27]. Furthermore, CPV 2 was also only identified in a benign viral papilloma case in the present study.…”

“…As for the canine PVs, CPV 1, 2, 3, 7, 12, 16, and 17 have been speculated to cause malignant transformation of the epithelium [1,28]. The association of viral antigens or genome with malignant lesions has also been demonstrated in CPV 1-, 2-, 12-, and 16-infected animals [26,27,29,33]. In the present study, we examined canine papillomas and canine SCCs taken from the oral cavity including the gingiva, lip, and tongue and demonstrated CPV 1 in four benign lesions.…”

“…Through contact with the infected canids, collective outbreaks of canine oral papillomatosis caused by CPV 1 have been reported in a daycare facility and a breeding farm [24,25]. Although some of the studies support that CPV 1 is unable to transform the cells, a recently published case report demonstrated that CPV 1 is highly associated with oral SCC [26,27]. Apart from CPV 1, the malignant transformations had been reported in CPV 2-, 3-, 7-, 12-, 16-, and 17-associated lesions [1,28,29].…”

“…The CPV 3 has been detected in a malignant canine epidermodysplasia verruciformis [31], and the genes of CPV 7, 12, and 16 were detected in cutaneous SCCs in dogs [32]. Among these CPVs, the associations of CPV antigens or nucleic acid with malignant lesions have been demonstrated and depicted in CPV 1, CPV 2, CPV 12, and CPV 16-infected animals by using either immunohistochemical staining (IHC) or in situ hybridization [26,27,29,33].…”

Severe persistent canine oral papillomatosis a multimodal approach including interferon alpha‐2B, CPV‐1 autologous vaccine, CO2 laser ablation and aggressive cryotherapy

“…It is believed that the use of an in-line suction as an appropriate smoke evacuation system and the potential aggressive freezing via cryotherapy intervention post-laser negated the risk of laser plume induced spreading of the viral disease. There is a report of a CPV-1-induced persistent oral papilloma that underwent malignant transformation into an oral squamous cell carcinoma 16. The possibility of a malignant transformation suggests using a more aggressive approach in extensive and persistent oral CPV growths as described in this case report.…”