Is there a role for Fusobacterium nucelatum, candida or HV16 in oral disease progression?

Oral squamous cell carcinoma (OSCC) accounts for over 90% of all oral cancers and is generally considered the 8th most common cancer worldwide [1]. Despite therapeutic advances, the 5-year survival rate is approximately 50%, making OSCC one of the most devastating malignancies [1]. Recognised risk factors for OSCC include tobacco and alcohol consumption [1]. However, many patients develop OSCC who lack these risk factors leading to speculation about the role of the oral microbiome in the development of OSCC.

Inflammation caused by infections has been suggested to be one of the most important preventable causes of cancers in general.[2] An additional mechanism in the bacteria–oral carcinogenesis interaction is explained by the highly carcinogenic acetaldehyde metabolism from alcohol by several oral micro-organisms.[3]

Fusobacterium nucleatum is a commensal of the human oral cavity which is associated with subgingival plaque and poor oral hygiene [4] and has been implicated as a driver of the progression of colorectal carcinoma [5,6]. Gallimindi et al. showed that P. gingivalis and F. nucleatum could promote oral carcinogenesis in a chemically induced (4NQO) murine model of OSCC. [7] A recent systematic review reported that Fusobacterium is present and in higher abundance in oral/head and neck cancer samples when compared to non-cancer samples, suggesting that Fusobacterium may contribute to oral/head and neck cancer development [8]. F. nucleatum can promote cancer by several mechanisms; activation of cell proliferation, promotion of cellular invasion, induction of chronic inflammation and immune evasion [9].

Yeasts, such as Candida, may invade oral epithelium and may also be causally involved in dysplastic changes. The potential of Candida to cause malignant transformation in oral mucosa has been reported.[10,11] Studies have shown a significantly higher degree of C. albicans colonisation in OSCC patients [12] and associations with the degree of dysplasia in potentially malignant oral lesions [13]. Studies have shown that these yeasts are genotypically different to carriage isolates from healthy patients [14,15]. This may have biological significance as C. albicans strains recovered from dysplastic tissue may have greater capacity to produce acetaldehyde and nitrosylating activity [16,17]. The impact of fungal colonisation on the bacterial microbiota may also be significant as Amer et al. [18] reported that Candida colonisation was associated with increased levels of F. nucleatum.

Human papilloma virus (HPV) is strongly associated with oropharyngeal cancers, however, a definitive association with oral cancers has yet to be proven. One study reported that 70% of oropharyngeal tumours (including 80% of tonsillar cancers) were HPV positive whereas in the same study only 20% of oral cancers were HPV positive [19]. More recently a study of 409 oral SCC showed positivity of high-risk HPV E6/7 oncogene expression in only 5.9% of cases [20]. Studies on oral dysplasia, a potentially malignant oral lesion, have reported a distinct subset of lesion positive for high risk HPV16. [22,22] Although a role for HPV in OSCC has not been definitively proven, the involvement of the HPV virus in a proportion of OSCC is possible.

The aim of the this study would be to determine the possible association between F.nucelatum, candida and HPV16 in oral disease progression by a comparison between normal oral mucosa, benign oral lesions, oral potentially malignant lesions (OPML) and OSCC. The prognostic impact of  would be investigated.

DNA would be extracted using commercially available kits and analysed for HPV16, candida and f. nucleatum. Protein expression would be determined in ex-vivo tissue by immunohistochemistry. Interesting samples will be sequenced to gain a better understanding of the aetiological agent involve

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