Detection of Equine Papillomaviruses and Gamma-Herpesviruses in Equine Squamous Cell Carcinoma

Abstract

Squamous cell carcinoma (SCC) seriously compromises the health and welfare of affected horses. Although robust evidence points to equine papillomavirus type 2 (EcPV2) causing genital lesions, the etiopathogenesis of equine SCC is still poorly understood. We screened a series of SCCs from the head-and-neck (HN), (peri-)ocular and genital region, and site-matched controls for the presence of EcPV2-5 and herpesvirus DNA using type-specific EcPV PCR, and consensus nested herpesvirus PCR followed by sequencing. EcPV2 DNA was detected in 45.5% of HN lesions, 8.3% of (peri-)ocular SCCs, and 100% of genital tumors, whilst control samples from tumor-free horses except one tested EcPV-negative. Two HNSCCs harbored EcPV5, and an ocular lesion EcPV4 DNA. Herpesvirus DNA was detected in 63.6%, 66.6%, 47.2%, and 14.2% of horses with HN, ocular, penile, and vulvar SCCs, respectively, and mainly identified as equine herpesvirus 2 (EHV2), 5 (EHV5) or asinine herpesvirus 5 (AsHV5) DNA. In the tumor-free control group, 9.6% of oral secretions, 46.6% of ocular swabs, 47% of penile samples, and 14.2% of vaginal swabs scored positive for these herpesvirus types. This work further highlights the role of EcPV2 as an oncovirus and is the first to provide information on the prevalence of (gamma-)herpesviruses in equine SCCs.

Equus caballus papillomavirus type 2 (EcPV2)‐associated benign penile lesions and squamous cell carcinomas

“…In 2020, EcPV2 nucleic acids were identified with ISH in 8 out of 68 horses (12%) in eyelid samples collected from asymptomatic Western Canadian horses (Greenwood et al., 2020 ), but not in ocular/periocular SCCs (Greenwood et al., 2020 ). Previously EcPV2 DNA has been detected in a periorbital SCC (Kainzbauer et al., 2012 ), and in two periocular SCCs (Miglinci et al., 2023 ). However, EcPV2 associated lesions in ocular tissues seem to be rare (Greenwood et al., 2020 ; Newkirk et al., 2014 ; Scase et al., 2010 ; Sykora & Brandt, 2017 ).…”

“…DNA has been recently detected in subsets of head-and-neck SCCs (HNSCC) in horses (Miglinci et al, 2023;Strohmayer et al, 2022). In humans, oropharyngeal SCCs are most often associated with HPV type 16 (Hibi et al, 2019;Zaravinos, 2014) The oncogenic mechanisms of EcPV2 have not yet been described in detail, but it is believed that both E6 and E7 oncogenes, which are the major viral oncoproteins of HPVs, may also play a role in carcinogenesis in horses.…”

“…Based on scattered reports of EcPV2 associated SCCs and our findings, underlying EcPV2 infection should be considered as a possible predisposing factor for ocular SCCs. Recently, DNA of equine herpesvirus types 2 and 5 (EHV2, EHV5) and asinine herpesvirus type 5 (AsHV5) have been detected in ocular SCCs and precursor lesions, but also relatively frequently in ocular swabs obtained from healthy horses, and the possible role of herpesviruses in the development of SCCs is yet to be determined (Miglinci et al., 2023 ). Unfortunately, our sample size was small and further studies are required to investigate the association of EcPV2 infection with ocular SCCs.…”

“…Previously, EcPV2 DNA was detected in a guttural pouch SCC of a horse with associated laryngeal and laryngotracheal SCCs and laryngeal papillomatous lesions and in a laryngopharyngeal SCC of a horse (Hibi et al., 2019 ; Lale et al., 2023 ). Additionally EcPV2 DNA has been recently detected in subsets of head‐and‐neck SCCs (HNSCC) in horses (Miglinci et al., 2023 ; Strohmayer et al., 2022 ). In humans, oropharyngeal SCCs are most often associated with HPV type 16 (Hibi et al., 2019 ; Zaravinos, 2014 ).…”

Highlights of recent clinically relevant papers

“…In this study, Lea Miglinci and co‐workers in Austria estimated the prevalence of equine papillomaviruses and gamma‐herpesviruses in equine squamous cell carcinoma (SCC) .…”