Feline viral papillomatosis

updated September 29, 2015

The feline viral papillomatosis guidelines were first published in J Feline Med Surg 2013; 15: 560-562; the present update has been compiled by Herman Egberink.

 

Virus

Fig. 1. Papilloma virions

Fig. 1. Papilloma virions

Papillomaviruses (PVs) are small viruses (55-60 nm capsid of ikosahedral symmetry; Fig. 1) with a monopartite, circular double-stranded DNA genome. The family Papillomaviridae presently (2015) contains 38 genera.

 

 

Epidemiology

 

Papillomaviruses cause cutaneous lesions in man and several animal species, including cats (Munday, 2010). In each host different papillomavirus types exist, which is also true for cats (Munday, 2008). The viruses tend to be species specific, but sequences related to bovine and human PVs have been found in cats, suggesting cross-species transmission (O’Neill 2011; Anis, 2010). To date, four feline PVs from domestic cats have been fully sequenced and classified (Munday, 2014). These viruses were designated as Felis domesticus PVs (FdPVs), but recently changed to Felis catus PVs (FcaPVs; Munday et al., 2013). Papillomavirus infection has also been detected in other felids including the Florida panther, Bobcat, Asian lion, Snow leopard and clouded leopard (Sundberg, 2000).

 

A clear association between Papillomavirus DNA (the Felis domesticus papillomavirus 2 – FdPV-2) and squamous cell carcinomas (SCCs) was reported; DNA was detected in all 20 bowenoid in situ carcinomas (BISCs) examined, and in 17 of 20 cases of invasive squamous cell carcinomas (ISCCs; Munday et al., 2008). However, FdPV-2 DNA was also present in 52 % of normal skin swabs (Munday and Witham, 2010). Although FdPV-2 has been detected most frequently in BISCs and SCCs, other PV types have also been identified. Recently, a novel PV type, designated FcaPV-3 was detected in a feline BISC (Munday et al., 2013). In one study, 50 % of the sequenced PV DNA was most closely related to human PV DNA. In another study, PV DNA could not be detected in any of 30 oral squamous cell carcinoma (OSCC) samples screened (Munday et al., 2011), which is at variance with earlier observations.

 

Pathogenesis

 

Papillomaviruses are epitheliotropic; infections usually occur through lesions or abrasions of the skin. Initially, the basal cells of the stratum germinativumare infected, which leads to hyperplasia and delayed maturation of cells in the stratum spinosum and granulosum. In the basal cells only early gene expression occurs, whereas viral protein synthesis and virion assembly occurs in terminally differentiated cells of the stratum spinosum and, more specifically, the stratum granulosum. Virus is present in the differentiated keratinized cells and is shed with exfoliated cells of the stratum corneum. Papillomaviruses are commonly found in normal skin of different animals, including the cat. This makes definite proof of a causal relationship between the presence of PV sequences and skin lesions difficult.

 

 

Clinical signs

 

In cats PVs have been associated with different skin lesions.

 

Fig. 2. Pigmented flat cutaneous papillomas (photo Herman Egberink, Ph.D. thesis Utrecht)

Fig. 2. Pigmented flat cutaneous papillomas (photo Herman Egberink, Ph.D. thesis Utrecht)

 

First, cutaneous hyperkeratotic plaques seem to be most common in older and immunosuppressed cats, e.g. FIV infected animals (Egberink, 1992; Carney, 1990). However, plaques have also been reported in cats without any recognized immunodeficiency (Wilhelm, 2006). The plaques appear as flat, slightly raised scaly and variably pigmented lesions (Fig. 2).

 

Second, viral plaques can progress into Bowenoid in situ carcinomas (BISCs), which can progress to invasive squamous cell carcinomas (ISCCs). Feline BISCs occur often in pigmented, haired skin and appear as crusting, hyperpigmented and roughly circular lesions. Sunlight plays a role in the development of ISCCs, where lesions are found more often than not in sparsely haired areas such as eyelids, nose and pinnae.

 

A clear association between Papillomavirus DNA (the Felis domesticus papillomavirus 2 – FdPV-2) and SCCs was found; it was detected in all 20 BISCs examines, and in 17 out of 20 cases of ISCCs. However, FdPV-2 DNA could also be detected in 52% of normal skin swabs (Munday, 2010). In one study 50% of the sequenced PV DNA was most closely related to human PV DNA. In a recent study, PV DNA could not be detected in any of 30 OSCC samples screened (Munday, 2011), which is at variance with earlier observations.

 

13 papillo JFMS Fig.2

Fig. 3. A case of sarcoid in a patient presented at the Utrecht Companion Animal Clinic; diagnosis was verified histologically, but the viral etiology was not established (courtesy Y.Schlotter, Companion Animal Clinic, Veterinary Faculty, Utrecht University)

 

Third, feline cutaneous fibropapillomas or feline sarcoids may be due to a  PV infection. They are rare, occurring as skin neoplasms, nodular masses found most commonly on the head, neck, ventral abdomen and limbs (Fig. 3.). The finding of a papillomavirus similar to bovine papillomavirus type 1, and the higher prevalence in cats with known exposure to cattle suggest an association with the bovine virus (Schulman, 2001; Munday, 2010). This hypothesis is in line with the known association between bovine PV and equine sarcoids.

 

Fourth, PVs have been associated with feline cutaneous papillomas (Munday, 2007).

 

 

Diagnosis

 

A biopsy from a skin lesion can be taken for histopathologic examination and immunohistochemical staining of papillomavirus group-specific antigens. By electron microscopy, intranuclear papillomavirus-like particles might be demonstrated in keratinised cells. Also PCR can be used to demonstrate PV DNA in the lesions and for identification of the viral strain by further sequencing. However, the presence of PV DNA in normal skin of cats makes interpretation of positive PCR results of skin lesions difficult.

 

 

Treatment

 

No specific treatment is known. In immunocompetent cats, spontaneous regression can be expected, as it also seen in dogs, but it takes a long time, up to several months. Feline invasive SCCs tend to slowly metastasize. Therefore, if anatomical location allows, complete excision might be curative.

 

 

References

 

Anis EA, O’Neill SH, Newkirk KM, Brahmbhatt RA, Abd-Eldaim M, Frank LA, et al. Molecular characterization of the L1 gene of papillomaviruses in epithelial lesions of cats and comparative analysis with corresponding gene sequences of human and feline papillomaviruses. Am J Vet Res 2010 Dec;71(12):1457-1461.

 

Carney HC, England JJ, Hodgin EC, Whiteley HE, Adkison DL, Sundberg JP. Papillomavirus infection of aged Persian cats. J Vet Diagn Invest 1990 Oct;2(4):294-299.

 

Egberink HF, Berrocal A, Bax HA, van den Ingh TS, Walter JH, Horzinek MC. Papillomavirus associated skin lesions in a cat seropositive for feline immunodeficiency virus. Vet Microbiol 1992 Jun 1;31(2-3):117-125.

 

Egberink H, Thiry E, Möstl K, Addie D, Bélak S, Boucraut-Baralon C, et al. Feline viral papillomatosis. ABCD guidelines on prevention and management. J Feline Med Surg 2013; 15: 560-562.

 

Munday JS. Papillomaviruses in felids. Vet Journal 2014; 199: 340-347.

 

Munday JS, Kiupel M. Papillomavirus-associated cutaneous neoplasia in mammals. Vet Pathol 2010 Mar;47(2):254-264.

 

Munday JS, Witham AI. Frequent detection of papillomavirus DNA in clinically normal skin of cats infected and noninfected with feline immunodeficiency virus. Vet Dermatol 2010 Jun;21(3):307-310.

 

Munday JS, Kiupel M, French AF, Howe L, Squires RA. Detection of papillomaviral sequences in feline Bowenoid in situ carcinoma using consensus primers. Vet Dermatol 2007 Aug;18(4):241-245.

 

Munday JS, French AF, Peters-Kennedy J and Howe L. Amplification of papillomaviral DNA sequences form a high proportion of feline cutaneous in situ and invase squamous cell carcinomas using a nested polymerase chain reaction. Vet Dermatol 2008; 19: 259-263.

 

Munday JS, Willis KA, Kiupel M, Hill FI, Dunowska M. Amplification of three different papillomaviral DNA sequences from a cat with viral plaques. Vet Dermatol 2008 Dec;19(6):400-404.

 

Munday JS, Knight CG, Howe L. The same papillomavirus is present in feline sarcoids from North America and New Zealand but not in any non-sarcoid feline samples. J Vet Diagn Invest 2010 Jan;22(1):97-100.

 

Munday JS, Knight CG, French AF. Evaluation of feline oral squamous cell carcinomas for p16CDKN2A protein immunoreactivity and the presence of papillomaviral DNA. Res Vet Sci 2011 Apr;90(2):280-283.

 

Munday JS, Dunowska M, Hills SF and Laurie RE. Genomic characterization of Felis catus papillomavirus-3: a novel papillomavirus detected in a feline Bowenoid in situ carcinoma. Vet Microbiol 2013; 165: 319-325.

 

O’Neill SH, Newkirk KM, Anis EA, Brahmbhatt R, Frank LA, Kania SA. Detection of human papillomavirus DNA in feline premalignant and invasive squamous cell carcinoma. Vet Dermatol 2011 Feb;22(1):68-74.

 

Schulman FY, Krafft AE, Janczewski T. Feline cutaneous fibropapillomas: clinicopathologic findings and association with papillomavirus infection. Vet Pathol 2001 May;38(3):291-296.

 

Sundberg JP, Van Ranst M, Montali R, Homer BL, Miller WH, Rowland PH, et al. Feline papillomas and papillomaviruses. Vet Pathol 2000 Jan;37(1):1-10.

 

Wilhelm S, Degorce-Rubiales F, Godson D, Favrot C. Clinical, histological and immunohistochemical study of feline viral plaques and bowenoid in situ carcinomas. Vet Dermatol 2006 Dec;17(6):424-431.

 

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