Papillomavirus infection of equids

Current authors:
C G KNIGHT - Associate Professor of Veterinary Pathology, BVSc, PhD, Dipl ACVP, Department of Veterinary Clinical and Diagnostic Sciences, Faculty of Veterinary Medicine, University of Calgary, 3280 Hospital Dr. NW, Calgary, Alberta, T2N 4Z6, Canada
J S MUNDAY - Professor of Veterinary Pathology, BVSc, PhD, Dipl ACVP, School of Veterinary Science, Massey University, Tennent Drive, Palmerston North, Manawatu, 4410, New Zealand

GENERAL INTRODUCTION: PAPILLOMAVIRIDAE

Introduction

Seven types of equine papillomavirus (Equus caballus papillomavirus; EcPV) infect horses.^{18, 31, 52} These are subclassified within the Zetapapillomavirus, Dyoiotapapillomavirus, or Dyorhopapillomavirus genera.⁴⁹ Three distinct clinical syndromes caused by EcPV infection are recognized: cutaneous papillomas, aural plaques, and genital lesions including squamous cell carcinomas (SCCs). In addition, infection with bovine deltapapillomaviruses is associated with a fourth clinical syndrome, the development of fibroblastic sarcoids in horses and other equids, including donkeys, mules and zebras. A single donkey papillomavirus (Equus asinus papillomavirus type 1; EaPV-1) has been described, although this virus is not currently associated with any clinical disease.³³

Cutaneous papillomas (viral warts, classical viral papillomatosis, “grass warts”)

Cutaneous papillomas are caused by Equus caballus papillomavirus type 1 (EcPV-1).^{18, 46} Papillomas affect horses throughout the world and, along with sarcoids, SCCs and melanomas, are one of the four most commonly reported skin tumors of horses.^{54, 63} Surveys of diagnostic laboratory submissions probably underestimate the prevalence of cutaneous papillomas because they are easily recognized by clinicians and so are seldom submitted for histologic diagnosis.⁵⁴ It is likely that, similar to other species, most horses develop papillomas during their lifetime.

Equus caballus papillomavirus type 1 is transmitted directly and indirectly through small skin abrasions, as is typical for papillomaviruses.^{10, 54} The incubation period after experimental inoculation ranges from two weeks to two months and lesions typically regress spontaneously after several months.^{10, 22} Congenital papillomas have been reported in foals; however, these are probably hamartomas (epidermal nevi) and are unlikely to be caused by papillomavirus infection.

Cutaneous papillomas usually develop on horses that are less than three years old, although they may occur in older horses, particularly in immunocompromised animals.⁵⁴ They develop most frequently on the muzzle and lips (Figure 1), less frequently on the distal limbs, eyelids, or paragenital region, and are uncommon in other body locations.⁵⁴ Papillomas are typically multiple, and as many as 100 may be present. When numerous papillomas develop they may coalesce into a single large mass. Lesions begin as 1 mm diameter, well-demarcated, smooth, greyish-white papules. Over a one to two-month period they proliferate and progress to larger (5-20 mm diameter), broad-based or pedunculated masses that are pink, grey or white and have roughened or frond-like surfaces composed of thickened keratin. Cutaneous papillomas are typically neither pruritic nor painful.

Histologically, cutaneous papillomas have three phases: growth, development and regression.²² Papillomas initially progress from basal cell hyperplasia and mild hyperkeratosis to marked, papillary epidermal hyperplasia with cellular features typical of papillomavirus infection such as enlargement of cytoplasm by increased quantities of blue-grey material, enlarged, darkened nuclei surround by a perinuclear clear space (koilocytosis), and intranuclear viral inclusion bodies. The regression phase is characterized by infiltration of lymphocytes and mild proliferation of fibroblasts.

Diagnosis is often straightforward as the gross appearance and location of lesions and the signalment of affected horses are characteristic. Biopsy and histologic examination are diagnostic but rarely performed. However, these are indicated when lesions are present in atypical body locations, as sarcoids and SCCs can appear clinically similar to cutaneous papillomas.⁵⁴

Cutaneous papillomas typically resolve without treatment in two to three months. However, as in humans, the time taken for resolution can be variable with a small proportion of papillomas persisting for up to a year prior to spontaneous resolution. If resolution has not occurred after 12 months, immunosuppression should be considered and investigated.⁵⁴ Immunity post-resolution is lifelong. If removal is required for cosmetic or medical reasons, surgical excision and cryosurgery are effective. There is no proof that surgical removal of a proportion of lesions accelerates the regression of remaining lesions.⁵⁶ Because cutaneous papillomas regress spontaneously without treatment it is difficult to interpret the results of therapeutic intervention. Suggested but unproven treatments include topical antiviral and “wart” creams, injection of intralesional or intravenous immunostimulants, injection of intralesional cisplatin or interleukin-2 (IL-2), and administration of autogenous vaccines.⁵⁴

Cutaneous papillomas are contagious and their spread may be reduced by isolating affected horses, reducing exposure of naive horses to infected premises and pastures, and disinfecting feeding, grooming...