Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and accounts for approximately 650,000 new diagnoses and 350,000 cancer deaths every year (Parkin, et al., 2005). In the United States, HNSCC accounts for approximately 5% of all cancer cases diagnosed per year. Even with significant advances in operative skills such as reconstructive microvascular free tissue transfer, and in adjuvant therapies such as hyperfractioned radiotherapy and concomitant chemoradiation, the 5-year survival of the HNSCC has not been markedly improved in the past three decades. The number of annually diagnosed cases amounts to over 42,000 individuals and results in more than 12,000 deaths per year in the United States. As is known, HNSCC is a locoregional disease notoriously for regional and distant metastases, representing the leading cause of death in HNSCC patients. Although surgical resection of isolated metastases is beneficial for some patients, the overall efficacy of surgery, chemotherapy or radiotherapy is still limited. The main reason for the poor 5-year survival may be that the most important prognostic factors for these patients are not only local control, but regional and distant metastases as well.