Influence of site and smoking on malignant transformation in the oral cavity: Is the microbiome the missing link?

Abstract

The tongue and floor of the mouth are high-risk sites for oral squamous cell carcinoma (OSCC), while smoking is its most significant risk factor. Recently, questions have been raised as to the role of the oral microbiome in OSCC because of a wealth of evidence demonstrating that the microbiome of OSCC differs from that of healthy mucosa. However, oral site and smoking also have a significant impact on oral microbial communities, and to date, the role these factors play in influencing the dysbiotic microbial communities of OSCC and precursor lesions has not been considered. This review aims to examine the influence of site and smoking on the oral microbiome and, in turn, whether these microbiome changes could be involved in oral carcinogenesis.

Oral squamous cell carcinoma: Effect of tobacco and alcohol on cancer location

“…There have been suggestions for causal factors of OTSCC, such as impaired immune system 9 and genetic origin (Li-Fraumeni syndrome, Fanconi’s anemia) 27 . Dysbiotic oral microbiome, apart from HPV, has been considered a predisposing factor in OTSCC 28 , but findings have remained unclear 29 . FOM carcinomas usually also have a low incidence of HPV-DNA, and HPV does not seem to have a significant role in the pathogenesis of FOM OSCC 30 .…”

“…Among the young, non-smoking patients with OTSCC, a significantly higher prevalence of oral leukoplakia has been identified 31 , which is considered a stronger risk factor for non-smokers than for smokers 32 . The tongue is the most common or the second most common site of oral leukoplakia (following buccal mucosa) and is considered a high-risk site for malignant transformation 28 . The differences in the etiology of these cancers remain partly unknown, but examining whether FOM has structural and/or molecular differences from the tongue that could attenuate the effect of these risk factors should be elucidated.…”

Real-Time PCR Detection of Candida Species in Biopsy Samples from Non-Smokers with Oral Dysplasia and Oral Squamous Cell Cancer: A Retrospective Archive Study

“…Chronic oral infectious conditions that result in chronic inflammation, especially chronic periodontitis [11,14] and poor oral hygiene [15], have been related to the development of oncological diseases. Recent research to identify the bacterial signatures in the oral microbiome of patients with oral squamous cell carcinoma (OSCC) implicated over-representation of, in particular, Fusobacterium, Porphyromonas, Capnocytophaga, Prevotella, and Peptostreptococcus species [11,[16][17][18][19][20][21][22], yet the determination of a conclusive causal relationship attributed to the oral microbiome has sparked controversy [23], probably due to the inherent disparities present in anatomical sites and methodologies of microbial sampling, and the diverse array of evaluative techniques employed [24].…”

Aberrant AHRR, ADAMTS2 and FAM184 DNA Methylation: Candidate Biomarkers in the Oral Rinse of Heavy Smokers

“…Smoking is known to affect the oral microbiome, with high levels of Gram-negative organism colonization in the tongue, a site with high rates of malignant transformation. Smoking is also the strongest factor in increasing microbial acetaldehyde production and reducing total salivary antioxidant capacity [9,10].…”