## 4 Oral Cancer  
Oral cancer is defined as squamous cell carcinoma of the lip, oral cavity and orophnx, and is the sixth most common malignancy in the world [36]. Patients with oral squamous cell carcinoma (OSCC) often have a poor outcome even though advances in treatment have been made. The 5 year survival rate is approximately 80% for early stage disease but only approximately 20% for late stage disease [37] and patients often present with advanced disease. Multiple primary tumours are common and second primary tumours are the most common cause of death in patients with early stage disease [38]. OSCC is a multi causal disease and risk factors include lifestyle habits (tobacco exposure and alcohol consumption), dietary factors, occupational activity, socioeconomic status, exposure to external agents, and genetic susceptibility [39,40]. Most cases of oral cancer occur in patients of 60 years or over and the risk increases with advancing age. The gold standard method for diagnosis of oral cancer and pre-malignant lesions is clinical examination and histopathological evaluation of biopsied tissue [41]. Conventional visual and tactile examination (CVTE) is used to detect OSCC and pre-malignant oral lesions in a screening setting but oral pre-malignant lesions and some early OSCC can be difficult to distinguish from inflammatory lesions. Most lesions are white patches known as leukoplakia and only approx. 4% of these lesions progress to cancer. CVTE cannot distinguish between these lesions and non-progressive lesions. Biopsy is followed by histopathology, where the excised tissue is processed, cut into sections and mounted on a glass slide for examination by a pathologist. Grading of tumours depends on the visual assessment of tissue architecture and characteristics of individual cells. The grading characteristics used are highly subjective and early proliferation/pre-malignancy may not be apparent morphologically. In addition, it can be difficult to discriminate between reactive/inflammatory lesions and pre-cancer lesions. A number of screening and diagnostic aids for early detection and diagnosis of oral cancer and pre-cancer have become available over the last decade including brush biopsy, toluidine blue vital staining, post-acetic acid rinse tissue reflectance and tissue autofluorescence. Some of these techniques show promise but as yet none has been definitively proven to perform better than conventional visual examination [42]. Well designed clinical studies are needed where the techniques are directly compared to the diagnostic gold standard, scalpel biopsy and histopathology. Early detection of cancer greatly increases the chances for successful treatment. There is a significant clinical need for new techniques that can detect pre-malignant changes that may progress to cancer. Oral cancer progression is not as clear cut as, for example, in cervical cancer in which there is a well-defined progression from mild to moderate to severe dysplasia (CIN 1, 2 and 3). The majority of histologically pre-malignant oral lesions do not progress to cancer at all and mild dysplasia can progress to cancer as readily as severe dysplasia. In a long term follow up of 236 patients with oral lesions, [PERSON] _et al._[43] found that the degree of dysplasia was not a predictor of malignant potential of the lesions. The inability of conventional histopathology to predict which lesions will progress to cancer underlines the need for new techniques or new technologies to address this clinical need. While a number of Raman spectroscopy studies have been carried out on oral tissues [44, 45, 46], to date, only a limited number of IR studies have focused on oral exfoliated cells. [PERSON] _et al._[47] showed that oral cells could be classified according to anatomical region with cells from cheek, palate and gums being spectrally similar whereas cells from the tongue and from the floor of the mouth were spectrally distinct due to an abundance of keratin and collagen respectively.