PROJECT SUMMARY/ABSTRACT Most head and neck cancer (HNC) patients receive high-dose radiation therapy (RT), which has significant, sometimes life-long, adverse effects on oral and maxillofacial tissues. Damage to salivary glands frequently leads to hyposalivation, increasing the risk of dental caries and tooth loss post-radiation. Furthermore, radiation impairs the ability of bone to heal, leading to a life- long risk of osteoradionecrosis (ORN), which presents as exposed intraoral bone and is often precipitated by dental extractions. Consequently, HNC patients are caught in a vicious circle, being at higher risk of needing dental extractions, but with extractions to be avoided post-RT due to the risk for ORN. A multi-center prospective cohort study, Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients (OraRad), was established to examine the incidence of oral complications after RT and associated risk factors in HNC patients. The OraRad cohort of 572 participants was followed for 24 months with incidence and risk factors of short-term oral complications identified. The overall objective of the current proposal is to assess OraRad participants at 7 years post-RT and identify the long-term incidence and risk factors of oral complications in this cohort. We will accomplish this objective by pursuing the following specific aims: 1) Determine the long-term incidence of dental caries, periodontal disease, tooth loss and osteoradionecrosis, up to 7 years after RT for HNC patients and 2) Determine the risk factors associated with high and low incidence of long-term oral complications and develop a multiple variable model of risk. We will accomplish these aims by having current OraRad participants return for a clinical oral examination at about 7 years post- RT. We anticipate 350 long-term OraRad survivors will be evaluated at this follow-up visit. The proposed research is innovative because this is the first prospective multi-center study with a large enough sample to identify risk factors associated with long-term adverse dental outcomes in HNC patients after modern RT. Our strong data on the incidence and risk factors of oral complications for the initial OraRad 24-month study period clearly demonstrate the feasibility of achieving these aims. This study is highly significant because it will directly provide data to facilitate evidence-based dental management of patients receiving current modalities of RT for HNC.