Inclusion Criteria:

1. Male or female ≥ 18 years
2. ECOG Performance Status ≤ 1
3. Histological evidence (from the primary lesion and/or lymph nodes) of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
4. Stage III or IV disease (T2N2-3M0, T3-4N1-3M0)
5. No evidence of distant metastases by CT or PET/CT scan
6. Life expectancy > 4 months
7. Neutrophil count ≥ 2,000/mm^3
8. Platelet count ≥ 100,000/mm^3
9. Hemoglobin ≥ 10 g/dL
10. Bilirubin ≤ 1.5 times ULN
11. AST and ALT ≤ 2.5 times ULN
12. Alkaline phosphatase ≤ 2.5 times ULN
13. Creatinine clearance ≥ 60 mL/min
14. Female patients of child-bearing potential (i.e. not surgically sterile, or not having spontaneous amenorrhea for at least 12 months) must agree to use an effective form of contraception during the treatment phase of the study.
15. Male patients must agree to use a condom with spermicide or their female partner must use an effective method of birth control.
16. Provide written informed consent in accordance with all applicable regulations and follow the study procedures. Patients must be capable of understanding the investigational nature, potential risks and benefits of the study.

Exclusion Criteria:

1. Prior treatment for locally advanced SCCHN (NO prior surgery for SCCHN except nodal sampling or biopsy for study disease).
2. Patients with T1-2N1 or T1N2-3.
3. Pre-existing peripheral neuropathy ≥ Grade 2 (motor or sensory).
4. Weight loss > 20% of body weight within 3 months of screening (unless purposeful).
5. Surgery ≤ 28 days before randomization with the exception of feeding tube placement, dental extractions, central venous catheter placement, biopsies and nodal sampling.
6. Cancer of the nasopharynx, sinus, salivary gland or skin.
7. Previous radical RT to the head and neck region, excluding superficial RT for a non-melanomatous skin cancer.
8. Prior cancers, except: those diagnosed > 5 years ago with no evidence of disease recurrence and clinical expectation of recurrence of less than 5%; or successfully treated non-melanoma skin cancer; or carcinoma in situ of the cervix.
9. Significant intercurrent illness that will interfere with the chemotherapy or radiation therapy such as HIV infection, cardiac failure, pulmonary compromise (chronic obstructive pulmonary disease, pneumonia or respiratory decompensation) resulting in hospitalization within 12 months of screening, or active infection.
10. Any significant cardiac disease (e.g., New York Heart Association (NYHA) Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary artery bypass graft (CABG) within the past 6 months; or uncontrolled atrial or ventricular cardiac arrhythmias..
11. High risk for poor compliance with therapy or follow up as assessed by the investigator.
12. Active herpes labialis, other lesions due to HSV1 or dermatoses involving or within 50 cm of the lesions to be injected; active HSV1 lesions must have resolved before OncoVEXGM-CSF is injected.
13. Prior systemic chemotherapy for any type of cancer.
14. Patients for whom radiation therapy is contraindicated.
15. Pregnant or breast-feeding female. Confirmation that women of child-bearing potential are not pregnant. A negative serum β- human chorionic gonadotropin (β-hCG) pregnancy test result must be obtained during the screening period.
16. Currently enrolled and receiving an investigational agent in a clinical research study or received an investigational agent for any reason within 4 weeks prior to screening.
17. Require intermittent or chronic treatment with an anti-herpetic drug (e.g., acyclovir), other than intermittent topical use.