Abstract: Dry mouth (xerostomia) is one of the most common and severe toxicities that patients experience after radiotherapy (RT) for head and neck cancer. Xerostomia results from RT-induced damage to the salivary glands and is associated with difficulties in chewing, swallowing, speaking, as well as increases in occurrence of dental carries, all decreasing the patient’s quality of life. Existing methods to prevent xerostomia are often not very helpful to the patient, difficult to implement, and can cause additional toxicities. In an attempt to reduce the morbidity of treatment, dose-reduced chemoradiotherapy regimens where patients with favorable-risk HPV-associated tumors are treated with 60Gy (Chera 2019) compared to the conventional 70Gy have been introduced. While dose reduction has led to an overall improved symptom profile, xerostomia remained the most severe patient-reported toxicity. Thus, additional methods to minimize RT- induced xerostomia are needed. Data suggest that salivary stem/progenitor cells, which preferentially reside within the large salivary ducts, have the potential to regenerate salivary glands post-injury. Our hypothesis is that dose sparing of the stem cells within the parotid ducts will improve patient outcomes compared to conventional parotid sparing (i.e., attempting to limit the mean dose of the contralateral parotid gland to less than 26Gy). In order to evaluate the utility of parotid ductal sparing formally, we will conduct a randomized double-blind trial. Patients with oropharyngeal squamous cell carcinomas will be randomized to receive parotid ductal sparing (using MRI-sialography to identify the ducts) or conventional parotid sparing RT.