## 3 Cervical Cancer  
Cervical cancer is the fourth most common cancer in women worldwide with an estimated 528,000 new cases and 266,000 deaths in 2012 [1]. The mortality associated with cervical cancer can be reduced if this disease is detected at the early stages of development or at the pre-malignant state (cervical intraepithelial neoplasia, CIN). Currently, a Papanicolaou test is used to screen for CIN and cervical cancer in the general female population. The Papanicolaou test (also called Pap smear, Pap test, cervical smear, or smear test) is a screening test used to detect cancer and pre-cancer in the ectocervix. A spatula or cytobrush is used to collect the cells from the cervix and after placing in liquid fixative, the cells are then collected on a filter and transferred to a slide and stained. The cells are examined for abnormalities under the microscope by highly trained personnel. The Pap test is an effective, widely used method for early detection of cervical cancer and pre-cancer. Despite a high specificity of 95%-98%, the sensitivity of the Pap test is reported to vary greatly from 74% to 96% [10]. Low grade dysplasia or CIN 1 can spontaneously regress without leading to cervical cancer. However some CIN 1 lesions progress to moderate (CIN 2) and subsequently severe dysplasia (CIN 3), finally progressing to invasive cancer [11]. An abnormal Pap smear is followed by colposcopy, biopsy and histological confirmation of the diagnosis. This involves the visual examination of histological sections by highly trained personnel. The grading characteristics are quite subjective and pre-malignancy may not be visually perceptible at all. Persistent infection with high-risk human papillomavirus (HPV) (e.g., HPV types 16, 18) is accepted as the major cause for the development of cervical pre-cancer and cancer [12]. HPV testing has recently been introduced in parallel with Pap smear screening for safe and cost-effective lengthening of the cervical screening interval due to its high-negative predictive values [13]. The HPV DNA test identifies high-risk HPV oncogene expression. However, this test is expensive, time-consuming and requires experienced technicians. Over the last decade, prophylactic HPV vaccines have been developed but despite the introduction of these vaccines, there is still a need for regular cervical screening, as the vaccines do not protect against all oncogenic HPV types. Additionally, some women may not benefit from the vaccines if there is a pre-existing HPV infection or they do not receive the complete number of doses (three doses over a 6-month period). After vaccination, women must still get routine Pap tests which can detect abnormal cervical growth regardless of what HPV type causes it to develop. The first investigations of cervical exfoliated cells using IR spectroscopy were in the early 1990's by [PERSON] and co-workers. They published a number of papers showing significant differences between normal, pre-cancer and cancer samples [14; 15; 16; 17]. These initial studies recorded spectra from cell pellets rather than from individual cells and a number of confounding factors such as polymorphs, endocervical columnar cells, metaplastic cells, cervical mucus and debris were subsequently identified [18]. Further investigations by other groups identified similar confounding factors such as inflammation, metaplasia, hormonal changes, metabolic activity, blood, mucus [19; 20; 21; 22; 23]. However, an important early study by [PERSON] and [PERSON] [24] showed that the FTIR spectra of morphologically normal exfoliated cells from women with dysplasia or cancer exhibit extensive IR spectroscopic changes. This finding was later confirmed by [PERSON] _et al._[25] who showed spectral changes in cytologically normal cells, most likely due to HPV infection. [PERSON] _et al._[26] employed attenuated total reflection (ATR) FTIR spectroscopy to show spectral differences between normal and low grade and high grade dysplasia cytology samples.