Safety of a Single Administration of AAV2hAQP1, an Adeno-Associated Viral Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in People With Irradiation-Induced Parotid Salivary Hypofunction

* INCLUSION CRITERIA: 1. At least 18 years of age 2. History of external beam radiation therapy for head and neck cancer, with a mean dose equal to or greater than 15 Gy to a parotid gland. 3. Abnormal parotid gland function as judged by both absence of unstimulated parotid salivary flow and a stimulated parotid salivary flow in the targeted parotid gland \>0 and \<0.3 mL/min/gland after 2% citrate stimulation. 4. No evidence of recurrence of primary malignancy by otolaryngology (ENT) assessment. Additionally, all patients must have been disease-free of head and neck cancer for at least 5 years, a status to be determined at pre-dose screening using negative clinical exams and PET and or CT imaging of the neck and chest. The anatomic subset of HPV positive oropharyngeal cancer may be enrolled after 2 years post completion of therapy. 5. Willingness to practice the required birth control method ("barrier" contraception, condoms, diaphragm) until AAV2hAQP1 is no longer detectable in their serum or saliva. 6. Women who cannot bear children (post-menopausal or due to a surgical intervention) also will be required to practice barrier birth control methods until AAV2hAQP1 is no longer detectable in their serum or saliva. 7. Ability to stay at the NIH hospital for the period of time necessary to complete each on-site phase of the protocol (3-5 days). 8. No history of allergies to any medications or agents to be used in this protocol. 9. On stable medications (greater than or equal to 2 months) for any underlying medical conditions at time of vector administration. EXCLUSION CRITERIA: 1. Pregnant or lactating women. Women of childbearing potential are required to have a negative serum pregnancy test at screening and a negative urine pregnancy test within 48 hours prior to gene infusion. 2. Any experimental therapy within 3 months. 3. Any active respiratory tract infection in the 3 weeks prior to day 1 of the protocol 4. Active infection that requires the use of intravenous antibiotics and does not resolve at least 1 week before Day 1. 5. Uncontrolled ischemic heart disease: unstable angina, evidence of active ischemic heart disease on ECG, congestive heart failure (left ventricular ejection fraction \< 45% on MUGA or echo) or cardiomyopathy. 6. Asthma or chronic obstructive pulmonary disease requiring regular inhaled or systemic corticosteroids. 7. Individuals with a history of autoimmune diseases affecting salivary glands, including Sjogren's syndrome, lupus, scleroderma, type I diabetes, sarcoidosis, amyloidosis, and chronic graft versus host disease. Organ specific autoimmune conditions may be included if clinically stable. 8. Use of systemic immunosuppressive medications (,i.e., corticosteroids). Topical corticosteroids are allowed. 9. Malignancy, other than head and neck, within past 3 years, with the exception of adequately treated basal cell or squamous cell carcinoma of the skin or in situ cervical carcinoma. 10. Active infections including Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection. 11. WBC \<3000/microL or ANC \<1500/microL or Hgb \<10.0 g/dL or platelets \<100,000/microL or absolute lymphocyte count less than or equal to 500/microL. 12. ALT and/or AST \> 1.5 times upper limit of normal (ULN) or alkaline phosphatase \>1.5 times ULN 13. Serum creatinine \> 2 mg/dL. 14. Serum bilirubin measurements (total, direct, indirect) that are outside of the normal range. 15. Individuals who are active cigarette smokers as determined by self-reporting. 16. Individuals who have an allergy to iodine or shellfish and thus are unable to have sialographic evaluations. 17. Individuals who have an allergy or hypersensitivity to glycopyrrolate 18. Individuals whose parotid duct(s) are not clinically accessible on screening sialography. 19. Individuals, who on sialography, have a distal stenosis that would impede vector delivery and, for the expansion cohort, those who have a parotid volume \>2.5 mL. 20. Significant concurrent or recently diagnosed (\<2 months) medical condition that, in the opinion of the Medically Responsible Investigator, could affect the patient's ability to tolerate or complete the study. 21. Live vaccines within 4 weeks of first infusion. 22. Individuals who have had an adverse response to prednisone (i.e. hallucinations). 23. Individuals with uncontrolled diabetes (HbA1c greater than 10%). 24. Individuals with untreated severe dental caries, pyorrhea, gingivitis, chronic radiation mucositis or ulceration, erythroplasia, leukoplakia or other pre-malignant conditions.