Head and neck squamous cell carcinoma (
HNSCC) is a heterogeneous
cancer that arises in the upper aerodigestive tract. Despite advances in knowledge and treatment of this disease, the five-year survival rate after diagnosis of advanced (stage 3 and 4)
HNSCC remains approximately 50%. One reason for the large degree of mortality associated with late stage
HNSCC is the intrinsic ability of
tumor cells to undergo locoregional invasion. Lymph nodes in the cervical region are the primary sites of
metastasis for
HNSCC, occurring before the formation of distant
metastases. The presence of
lymph node metastases is strongly associated with poor patient outcome, resulting in increased consideration being given to the development and implementation of anti-invasive strategies. In this review, we focus on select
proteins that have been recently identified as promoters of
lymph node metastasis in
HNSCC. The discussed
proteins are involved in a wide range of critical cellular functions, and offer a more comprehensive understanding of the factors involved in
HNSCC metastasis while additionally providing increased options for consideration in the design of future therapeutic intervention strategies.