Submitted by: Patricia Shea, DVM
Viruses 2020;12: pii: E124. DOI: 10.3390/v12010124
Identification of a novel papillomavirus associated with squamous cell carcinoma in a domestic cat
Carrai M, van Brussel K, et al.
Squamous cell carcinoma (SCC) is the most common cutaneous malignancy in domestic cats, and is generally locally invasive and relatively slow to metastasize. Evidence is now accumulating that papillomaviruses, which are small, non-enveloped, double-stranded DNA viruses, may be associated with feline cutaneous SCCs. Papillomaviruses infect the skin and mucosa of a wide variety of vertebrate animal species including cats, dogs, and humans, and tend to be host-specific. Not all papillomaviruses are pathogenic, but those that are may be associated with a wide range of cutaneous diseases from benign lesions to significant cutaneous malignancies.
As with many infectious agents, the capacity of specific papillomaviruses to cause cutaneous tumors depends on their genotype, host factors such as immune status, and environmental factors, including sunlight exposure. Hitherto five papillomavirus genotypes of domestic cats have been identified. One of these genotypes, FcaPV2, is involved in a subset of cutaneous SCC in cats, but other papillomaviruses may also play a role in these tumors. Oral papilloma’s in cats are caused by FcaPV1, while FcaPV 2, 3, and 5 are causal in viral plaques and Bowenoid in situ carcinomas.
This case report describes the identification of a novel feline papillomavirus, Felis catus papillomavirus 6 (FcaPV6), discovered via metagenomic DNA sequencing of the nasal planum biopsy of a 10 year-old male neutered domestic shorthair cat who had both an invasive, recurrent SCC in this area, as well as a high-grade B cell lymphoma of the nasal cavity, discovered on a computed tomographic examination of the head and subsequently biopsied. The newly identified papillomavirus had a DNA sequence most similar to FcaPV3, but the sequences of these two viruses were still only 66.1% similar. Therefore, the newly discovered virus was considered to represent a new genotype, FcaPV6.
The cat, who tested positive for feline immunodeficiency virus (FIV) with no history of prior FIV vaccination, and negative for feline leukemia virus (FeLV) on retrovirus serology, also developed bilateral renomegaly and was euthanized several months later. Histopathology of renal tissues harvested after necropsy also demonstrated lymphoma.
In addition to the nasal planum biopsy from which the FcaPV6 was sequenced, an archived excisional biopsy of the cat’s SCC taken 20 months prior was intensely positive on p16 immunohistochemical staining. Strongly positive p16 immunostaining indicated a papillomaviral etiology for SCCs in both humans and cats. DNA extracted from this older, archived nasal planum biopsy tested positive for FcaPV6, and FcaPV6 was the only papillomavirus detected from DNA obtained from the SCC. The investigators felt it worthwhile to test the renal lymphoma for papillomavirus as it had arisen at a site distant from the two different nasal tumors. This was to see if there might be an association between papillomavirus infection and lymphoma. No papillomaviral DNA was found in the renal lymphoma lesion tested.
This novel feline papillomavirus was found in association with a SCC in a single individual. In order to learn more about the role of FcaPV6 in cutaneous neoplasia in cats, future studies need to focus on a larger number of cutaneous lesions as well as normal feline skin.
J Am Vet Med Assoc 2020; 256: 681-686. DOI: 10.2460/javma.256.6.681
Investigation of Schirmer tear test-I for measurement of tear production in cats in various environmental settings and with different test durations
Sebbag L, Uhl LK, et al.
Aqueous tear production is essential for ocular health; “dry eye”, the condition associated with aqueous tear deficiency, can lead to serious ocular pathology if undiagnosed and untreated. The Schirmer tear test (STT), in which the end of a calibrated paper strip is placed in the ventral conjunctival fornix of the eye for one minute, is used to measure tear production in both cats and dogs. It is easy to imagine that this could be difficult in many cats, and some experts have stated that the high sympathetic tone most cats experience during veterinary visits artifactually reduces tear production, rendering the STT inaccurate in feline patients. Moreover, far less is known about tear deficiency in cats.
This study of 176 cats in a variety of clinical settings, including private veterinary practice (n = 100), a feral cat clinic (n = 56), and a veterinary teaching hospital (n = 20), was initiated to address some of these concerns:
- The reliability of the STT in cats in different clinical settings.
- The influence of sympathetic stimulation on STT results.
- The possibility that the STT strip could still yield reliable feline tear production measurements if placed in the conjunctival fornix for less than one minute.
All patients enrolled in the study were evaluated and determined to be free of ocular surface disease and had no ocular discharge, conjunctivitis, or keratitis.
The cats enrolled in the teaching hospital portion of the study were staff or student-owned and used to frequent human contact; the feral cats came from barns or shelters and had little or no human contact prior to enrollment in the study. Those cats evaluated in private practices were presented for non-ocular reasons, and owners were present for the STT. The STT was performed on both eyes in all enrolled cats, so a total of 352 eyes were tested.
The 20 cats evaluated at the teaching hospital were subjected to two sets of STTs performed on both eyes. The first set of tests was performed in a quiet room, and the second test was performed in the same room after sympathetic stimulation, which consisted of a recording of loud dog barking, augmented with periodic sharp noise generated by hand cymbals. In this portion of the study, the cat’s heart rate was determined with a stethoscope before and after the STT was performed.
No significant difference in STT measurements was found between right and left eyes 30 or 60 seconds after starting the test in all of the testing groups. The cats at the teaching hospital, who underwent additional STT testing after sympathetic stimulation, demonstrated significant increases in heart rate after this stimulation compared to their initial heart rates. However, STT results did not differ significantly between stimulated and non-stimulated conditions at any of the 6 incremental 10-second readings up to 60 seconds total.
Findings of this study therefore proved that increased sympathetic tone due to stress does not artifactually reduce tear production in cats. Also, importantly, placement of the STT strip for less than 60 seconds can result in valid test results in cats. The STT results obtained 30 seconds and 60 seconds after strip placement were very strongly correlated; however, the authors recommend that the strip be placed for the full, conventionally recommended minute if the cat will tolerate this.
The authors recommend that the STT should be performed as part of the feline ophthalmic examination, especially if there is evidence of ocular surface disease. However, a single low STT reading in a cat does not justify lifelong treatment for “dry eye”; the test results must be interpreted in the light of the patient’s clinical signs, and the STT should be repeated at subsequent evaluations to monitor trends in suspected aqueous tear deficiency.