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Feline oral squamous cell carcinoma (FOSCC) is the most common oral neoplasia in cats. This malignant tumor is locally invasive, has a high mortality rate, and its etiology is not yet known.
- cat
- oral cavity
- squamous cell carcinoma
1. Introduction
Squamous cell carcinoma (SCC) is the most common malignant oral tumor in cats. In general, feline oral squamous cell carcinoma (FOSCC) grows fast and is locally invasive, causing destruction of oral tissues [1,2]. The survival rate of cats affected by oral SCC has not improved over recent decades and the prognosis remains poor independently of the treatment instituted [3,4,5,6,7]. Considering the similarities in incidence, tumor biology, therapy, and prognosis, FOSCC has been proposed as a spontaneous model for human head and neck squamous cell carcinoma (HNSCC) [8,9]. HNSCC is the sixth most common human cancer and risk factors include tobacco, alcohol consumption, chronic inflammation, and human papilloma virus [10].
Despite the intense scientific research on this tumor, its etiology remains unclear.
2. Relationship of Oral SCC with Other Comorbidities
The PRISMA flow chart for the selected articles used in this systematic review can be seen in Figure 1.
Figure 1. PRISMA flow chart for study selection.
Six hundred and twenty-eight references were obtained in the initial search made on PubMed/MEDLINE’s database, in September of 2022. After title and abstract screening, 454 articles were excluded and 174 articles were selected for final full text review, which referred to (i) cats with oral SCC, including those whose main objective of the study was not the etiology, (ii) cats with oral SCC, but without referencing the specific location, and (iii) cats with oral neoplasia, but the type of tumor was not referenced.
After the full reading of the 174 selected studies, only 26 original studies were included in this critical review. One hundred and forty-eight studies were excluded for the following reasons: (i) no etiological factor of the disease was studied (n = 82), (ii) articles of literature review (n = 14), (iii) studies using cell lines of FOSCC and not related to clinical trials (n = 7), and (iv) no FOSCC biopsy was included or the location of the lesion was not referred to (n = 45).
The collected data from the 26 studies included are summarized. Regarding the etiological factors associated with feline squamous cell carcinoma: (i) 19 articles identified and studied the following virus: feline PV, human PV 38 (HPV38), feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), feline syncytial virus, torque tenovirus (TTV), human herpesvirus type 4, and feline herpesvirus type 1 (FHV- 1); (ii) 4 articles studied the association between exposure to environmental tobacco smoke and the development of FOSCC; (iii) 4 articles investigated the association between FOSCC and diet, deworming methods, and other factors, such as the source of heating, water, and the environment in which the animals lived and exposure to sunlight, and (iv) 4 articles reported comorbidities with expression in the oral cavity that may be associated with the development of the disease.
The studies included in this critical review were carried out in the following countries: United States of America (n = 12), Italy (n = 7), United Kingdom (n = 2), New Zealand (n = 4), Slovenia (n = 1), and Japan (n = 1).
The selected studies evaluated, in their entirety, 669 cats with oral SCC, and the number of samples ranged between 1 and 113 individuals/samples. Breed could not be identified in 476 of the 669 cats. The remaining 158 were from pure breeds: Abyssinian (n = 1), Burmese (n = 1), Chartreux (n = 8), Himalayan (n = 6), Maine Coon (n = 5), Persian (n = 2), Siamese (n = 3), European Shorthair (n = 306), Korat (n = 1), and unspecified purebred cats (n = 2).
Information on the gender was only available for 437 cats, including 258 females and 233 males. Gender was not recorded/referred to for the remaining cats. Patient ages ranged between 2 and 20 years.
In seventeen studies that researched about viruses, four used only PCR (polymerase chain reaction), eight used PCR and immunohistochemistry (IHC), two used PCR and in situ hybridization (ISH), and one used PCR and ViroCap (next generation sequencing method). In two studies, the research method was not mentioned. Concerning the research of viral agents, 13 publications focused on the research of papillomavirus (PV).
In seven studies, PV detection was performed by PCR and IHC, in four by PCR, in one by IHC, PCR, and ISH, in one by PCR and ViroCap, and another by PCR and ISH. These 14 studies evaluated a total of 292 cases of FOSCC, with PV being detected in 43 cases (14.7%). The incidence of PV ranged between 0 and 100%. The most identified genotype was Felis catus papillomavirus-2 (FcaPV-2), and (FcaPV-1), -3 (FacPV-3), and -4 (FcaPV-4) genotypes have also been reported, as well as human papillomavirus type 38.
The association between exposure to environmental tobacco smoke and the development of FOSCC was described in three studies. From a total 185 cats with FOSCC, this exposure was verified in 61 animals (32.9%). In two of these four studies [12,13], p53 expression was analyzed by IHC, which was observed to be increased in 32 samples (68.1%) out of a total of 47.
In relation to the two studies in which the association between oral SCC and type of diet was evaluated, 159 cats were included [12,14]. About 58.5% of these animals ate canned food, 56.6% canned tuna, and only 22% ate dry diet. In these same two studies, the association between FOSCC and the administration of deworming products was also evaluated, and it was observed that in 26 of the 159 (16.35%) cats used deworming collars.
Regarding the relationship of oral SCC with other comorbidities, among the 485 cats with this disease referred to in the studies included in this CR, thirty-one cats (6.4%) had dental pathology, but only one was referred to with diagnosis of feline chronic gingivostomatitis; one cat had an infection by Trichinella spp. and another was reported with an osteosarcoma.
3. Conclusions
Viruses can play a crucial role in oral carcinogenesis, due to its prooncogenic effect or by triggered immunosuppression which allows neoplastic proliferation. There is not enough evidence for the oncogenic role of PV in FOSCC or the hypothesis for using p16 expression as a marker for the presence of PV in this tumor.
Chronic exposure to environmental factors may be at the origin of FOSCC, also conjugated with virus etiology. The bibliography has a hypothesis that cats feed with canned food and those which use deworming collars have a higher risk to develop FOSCC.
Periodontal diseases and chronic inflammation in the feline oral cavity are frequent, and in analogy with what has been described for humans, it is important to understand their relationship with FOSCC.
The results researchers obtained showed that the available evidence on the etiology of FOSCC is still limited, however, there is a need to expand studies in this area, given the increasing interest in this topic.
This entry is adapted from the peer-reviewed paper 10.3390/vetsci9100558
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