Unraveling the Risk Factors and Etiology of the Canine Oral Mucosal Melanoma: Results of an Epidemiological Questionnaire, Oral Microbiome Analysis and Investigation of Papillomavirus Infection

Abstract

Oral mucosal melanoma (OMM) is the most common oral cancer in dogs and is very aggressive in this species; its risk factors and etiology are yet to be determined. This study aimed to unravel the risk factors for the development of OMM in dogs and to investigate the possible presence of papillomaviruses as an etiological factor. A case-control study was conducted in 15 dogs with OMM and 15 paired controls whose owners answered an epidemiological questionnaire. Oral swabs from the same dogs were subjected to 16S rRNA sequencing for microbiome analyses. In addition, DNA fragments of OMM had their DNA extracted and amplified by polymerase chain reaction in an attempt to detect canine papillomaviruses. The gingiva was the most frequent anatomical site (47%) of OMM, and most tumors were stage III when diagnosed. Most dogs bearing OMM and the controls had grade 3 periodontal disease, and this factor, along with tartar treatment and tooth brushing, did not differ between cases and controls. Most dogs with OMM and most controls had contact with smokers; there was no statistically significant difference. Canine papillomaviruses were not detected among OMM cases. Tannerella forsythia and Porphyromonas gingivalis were significantly increased in case dogs compared to the controls. As these bacteria are reportedly involved in the pathogenesis of periodontal disease and esophageal cancer in humans, we suggest that they might be risk factors for the development of canine OMM. The limitations of this study include the low number of dogs, and therefore, further studies on canine OMM with larger numbers of animals are encouraged.

Isolation of Oral Bacteria, Measurement of the C‐Reactive Protein, and Blood Clinical Parameters in Dogs with Oral Tumor

“…Oral anaerobic bacteria such as Porphyromonas spp., Fusobacterium spp., Bacteriodes spp., Capnocytophaga spp., Prevotella spp., Tannerella spp., Treponema spp., and Actinomyces spp. reported in the previous study [ 29 , 31 , 48 , 70 , 77 , 79 , 80 ] were not found in our study. Some bacterial isolates have been detected from the environment, as the channel of a dog's mouth is exposed to the outdoor environment.…”

“…They found that Tannerella forsythia and Porphyromonas gingivalis from the subgingival plaque samples were significantly increased in canine oral melanoma dogs compared to the control dogs. These bacterial species are related to the periodontal diseases and human esophageal cancer [ 48 ]. So far, there are few studies that compare the oral bacteria of healthy dogs and dogs with oral cancer.…”

The human and animals’ malignant melanoma: comparative tumor models and the role of microbiome in dogs and humans

“…In humans, tumor-associated microbiomes have been identified in several cancers including one study in cutaneous melanomas [123]. There is only one study in COM; it identified bacteria ( Tannerella forsythia and Porphyromonas gingivalis ) that in humans are key for the development of periodontal disease and esophageal cancer [214].…”

A Comparison of the Oral Microbiota in Healthy Dogs and Dogs with Oral Tumors

“…While there is evidence on the association between microbiota and neoplastic diseases in dogs [33][34][35][36][37], data on oral bacteria contribution to tumorigenesis in animals is limited. In a study that investigated the risk factors and etiology of the canine oral mucosal melanoma (OMM) in dogs, 16S rRNA sequencing was used for microbiome analyses and found that the bacteria Tannerella forsythia and Porphyromonas gingivalis were found in significantly higher amounts in dogs with OMM and their presence could be considered a risk factor for the development of OMM in dogs [37]. Stashenko et al [35] colonized germ-free mice with different oral microbiomes and exposed them to a carcinogenic 4-nitroquinoline-1-oxide (4-NQO) agent.…”