This clinical trial studies widefield fluorescence and reflectance imaging, fluorescence spectroscopy, and tissue samples in regularly examining (monitoring) participants at risk for developing oral cancer. All tissue and cells are made of tiny particles. Some of these particles give off small amounts of light. This light is called fluorescence. Fluorescent imaging use instruments that shine different wavelengths (colors) of light in the mouth taking fluorescence pictures through a portable head light or by taking fluorescent and reflectance pictures through a dental microscope using a digital camera. Fluorescent spectroscopy uses a small probe placed gently against the lining of the mouth and the tissue is exposed to small amounts of fluorescent light that is then collected with a special camera and a computer to be analyzed. Checking mouth tissue samples under a microscope may also help detect abnormal cells. Diagnostic procedures, such as fluorescence and reflectance imaging, fluorescence spectroscopy imaging, and tissue samples, may help doctors detect pre-cancer or early cancer when it may be easier to treat.

PRIMARY OBJECTIVES:

I. To compare images of oral mucosa, obtained at various wavelength combinations including 350 nm, 380 nm, 400 nm, and 450 nm excitation, to standard white light images, pathologic analysis of any biopsied tissue when available, and carcinogenic progression.

OUTLINE:

Participants' oral cavities are inspected by a clinician using a standard white light headlamp. Participants then undergo oral mucosa examination using wide-field reflectance and fluorescence imaging, and/or fluorescence spectroscopy imaging. Standard oral brush biopsies are also performed and examined microscopically. Participants may undergo repeated imaging procedures and biopsy during subsequent follow up visits.

Inclusion Criteria:

• Subjects with premalignant lesion, or potentially premalignant lesion, of the oral cavity mucosa (leukoplakia or erythroplakia)
• Patients with a history of head and neck cancer or oral premalignant disease but without any clinical evidence of disease
• Persons with any other condition (such as lichen planus, Fanconi anemia, heavy tobacco use, etc) making them at higher risk for oral cancer development
• Patients with either pre-malignant or a history of oral cancer based on patient history and clinical presentations

Exclusion Criteria:

• Subjects under the age of 18.
• Subjects that are unable or unwilling to give informed consent