Oral and oropharyngeal squamous cell carcinoma (OSCC), ranking as the sixth most prevalent cancer globally, is especially prevalent in low- and middle-income countries (LMICs). The high mortality rate in these regions is largely due to late diagnosis and delayed treatment, leading to advanced disease at the time of discovery. Building on the achievements of two NIH UH projects and a Phase I SBIR project, Light Research Inc (LRI) aims to develop and bring to market an innovative mobile oral-cancer screening and treatment (MOST) system, tailored for low-resource settings (LRS). This system integrates dual-modal oral cancer screening technology with photochemistry-based, FDA-approved photodynamic therapy (PDT). The project involves three aims: optimizing the MOST system for human studies (Aim 1), establishing the system for image-guided PDT using animal models (Aim 2), and evaluating the system for imaging and treating highrisk oral premalignant lesions (OPML) and early-stage oral cancer (Aim 3). The significance of this project lies in its potential to facilitate early detection and prompt treatment of oral cancers, thereby mitigating disease progression, reducing morbidity and mortality, and lowering healthcare costs. It specifically targets the critical challenge of screening high-risk populations and treating patients with high-risk OPML and early-stage oral cancer in LRS.