Noninvasive diagnosis, whether by sampling body fluids, body scans, or other technique, has the potential to simplify early cancer detection. A classic example is Pap smear screening, which has helped to reduce cervical cancer 75% over the last 50 years. No test is error-free; the real concern is sufficient accuracy combined with ease of use. This paper will discuss methods that measure gene expression or epigenetic markers in oral cells or saliva to diagnose oral and pharyngeal cancers, without requiring surgical biopsy. Evidence for lung and other distal cancer detection is also reviewed. 1. Introduction This year half a million people will be diagnosed with oral squamous cell carcinoma (OSCC) or oropharyngeal cancer, and about one quarter of that number will die from the disease, often disfigured from treatment. Cure rates have improved only slightly over the decades. Paradoxically, while early curable lesions are visible in the mouth, they are seldom diagnosed. Because oral and oropharyngeal cancers are often asymptomatic until the final stages, improved screening to detect cancerous lesions in the oral cavity is a key component to reducing this cancer [1]. Detection of suspicious oral lesions by a general dentist includes a visual inspection of the oral mucosa and visible throat. The clinician looks for either nonhomogenous or verrucous surfaces, of unknown cause, whitish or reddish in color. The examination of the oral cavity can be aided by toluidine blue vital staining, because the dye is retained in cells with malignant changes, or by the use of a fluorescent light source as premalignant and malignant lesions may differ from normal mucosa in their production of fluorescence [1]. On the detection of a suspicious lesion (of duration over 2 weeks), the patient may be advised to make an appointment with an oral surgeon so the lesion can be biopsied. The histopathological examination of a stained tissue section by a pathologist is the gold standard for diagnosis of oral neoplasia. A diagnosis is made based on changes in cell and nuclear size and mucosal architecture. Problems with this procedure include the difficulty for all but the most experienced practitioners to know which part of a heterogeneous lesion should be sampled, the need for multiple biopsies, the preference of only some dentists and physicians to perform oral biopsies, the refusal of some patients to submit to oral biopsies, and the subjective nature of the pathological analysis. The invasive nature and skill required to perform the procedure limit its usefulness as a part of oral
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