This is a Phase II, multicenter, open label, multi-national, randomized study to evaluate effectiveness and safety of two treatment regimens of Ad5CMV-p53 administered by intratumoral injections in patients with recurrent SCCHN squamous cell carcinoma of the head and neck. Patients will be randomized to one of two treatment regimens. The specific aims of this study are to estimate the objective response rate (CR+PR) of Ad5CMV-p53 in patients with recurrent SCCHN, for each of the two treatment regimens. Secondary, to evaluate the duration of response time to disease progression and overall survival in patients with recurrent SCCHN treated with Ad5CMV-p53 in reducing cancer morbidity in each of the two treatment regimens.