Detection of Felis catus papillomavirus type‐2 DNA and viral gene expression suggest active infection in feline oral squamous cell carcinoma

Abstract

Papillomavirus (PV) infection is associated with development of epithelial cancer in different species, including domestic cat (Felis catus). Felis catus PV type-2 (FcaPV-2) is considered the causative agent of a proportion of feline cutaneous squamous cell carcinoma (SCC), through the transforming properties of its E6 and E7 oncogenes. However, the possible role of FcaPVs in the aetiology of feline oral SCC (FOSCC) is still unclear. The aim of this study was to assess the presence and gene expression of FcaPV-2 in FOSCC samples. We detected FcaPV-2 DNA in 10/32 (31%) of the analysed FOSCC by the use of PCR methods. Importantly, viral mRNA was detected by RT-PCR in 7/10 (70%) of DNA positive samples. In particular, FcaPV-2 L1, E2 and E6E7 genes were found to be expressed in 5/10 (50%), 3/10 (33%) and 5/10 (50%) samples, respectively. Viral DNA was also detected in non neoplastic oral ulcerative lesions (ULs) (4/11, 36%); qPCR suggested a difference in viral load between ULs and FOSCCs, particularly in those expressing E6E7, although it was not statistically significant. These data suggest, but do not definively prove, a possible role of FcaPV-2 in the development of a proportion of FOSCC. Moreover, L1 and E2 gene expression results indicate that FcaPV-2 infection associated with these tumours may possibly be productive.

Telomerase Reverse Transcriptase (TERT) Expression, Telomerase Activity, and Expression of Matrix Metalloproteinases (MMP)-1/-2/-9 in Feline Oral Squamous Cell Carcinoma Cell Lines Associated With Felis catus Papillomavirus Type-2 Infection

“…For instance, HPV-16 E6 induces overexpression of cMyc, which is a transcriptional activator of TERT promoter (9). Recent studies demonstrate that a proportion of FOSCCs is associated with FcaPV-2 infection; importantly, FcaPV-2 biological activity has been previously revealed also in SCCF2 and SCCF3, with this latter cell line harboring higher E6 mRNA amounts (24,26). In this study, expression levels of cMyc, but not TERT, appeared to be correlated with those of E6 in SCCF cells; at first glance, these data suggested that the viral oncogene may up-regulate cMyc as in human counterpart, but this would not contribute to cell transformation through induction of TERT expression in FcaPV-2-related FOSCC.…”

“…It has been recently demonstrated that a sub-group of FOSCC is associated with Felis catus papillomavirus type-2 infection (FcaPV-2), whose oncogenes show transforming abilities comparable to those of HPV-16, thus mimicking HPVrelated hOSCC (22)(23)(24)(25)(26). However, the possible role of FcaPV-2 E6 in the regulation of telomerase and MMPs is still unknown.…”

Cutaneous vs. Mucosal Tropism: The Papillomavirus Paradigm Comes to an “and”

“…Studies of feline PVs indicate that the same virus can be associated with development of cancers of the skin and mucosal epithelia. Felis catus PV type 2 (FcaPV-2), originally isolated from and then widely associated with pre-neoplastic and neoplastic skin lesions, is detectable in a subset of feline oral squamous cell carcinoma (FOSCC) samples and FOSCC-derived cell lines, where it is transcriptionally active (Lange et al, 2009 ; Altamura et al, 2018a , 2020 ; Munday et al, 2018 ). Accordingly, molecular studies clearly show that FcaPV-2 E6 and E7 oncogenes display biological properties similar to those of mucosal HR HPV-16 in degrading p53 and pRb tumor suppressor proteins (Altamura et al, 2016 , 2018a ).…”

“…Accordingly, molecular studies clearly show that FcaPV-2 E6 and E7 oncogenes display biological properties similar to those of mucosal HR HPV-16 in degrading p53 and pRb tumor suppressor proteins (Altamura et al, 2016 , 2018a ). Possible transmission routes between the two anatomical sites have also been hypothesized, such as via skin licking or through the bloodstream carrying viral particles to the epithelium of oral cavity (Altamura et al, 2018b , 2020 ). Of note, other FcaPVs are suspected to infect skin and oral epithelia, such as FcaPV-1, -3, and -4 (Munday and French, 2015 ; Munday et al, 2015 , 2018 ; Mazzei et al, 2018 ; Vascellari et al, 2019 ; Chu et al, 2020 ), however additional experimental data are warranted for any confirmation.…”

Computed Tomographic and Histopathological Characteristics of 13 Equine and 10 Feline Oral and Sinonasal Squamous Cell Carcinomas

“…Many studies in human medicine are addressing the association between human papillomavirus infection and HNSCC (39). In cats, accumulating studies are also focusing on molecular biology and the relationship with papillomavirus infection (8,33,40). Studies have also evaluated using cats as animal models for studying emerging targets in human cancer therapy (41).…”