Head and Neck Cancers: Why Is It Better to HPV than Not to HPV?

Abstract

Objectives:

Dissect the impact of human papillomavirus (HPV) on angiogenesis in head and neck cancers (HNSCC).

Methods:

We analyzed 18 newly diagnosed HNSCC patients and controls. HPV tumor status was ascertained by p16 staining. Eleven pro- and anti-angiogenic factors were quantified in sera using a multiplex assay. Angiogenic factors were analyzed in the tumor tissue using immunohistochemistry.

Results:

We found that circulating levels of anti-angiogenic factor endostatin were higher in all HNSCC patients compared with healthy subjects irrespective of HPV status. Notably, we detected higher levels of the proangiogenic factors angiopoetin-1 and vascular endothelial growth factor (VEGF) in the circulation of HPV-negative patients compared with patients with HPV-positive tumors. Interestingly, levels of thrombospondin-2, an antiangiogenic factor, were lower in the circulation of patients with HPV-positive compared with HPV-negative tumors and healthy controls. We next analyzed these angiogenic factors in the tumor tissue. Interestingly, while HPV-negative tumors exhibited VEGF expression both in tumor tissue and stromal cells, only a fraction of HPV-positive tumors exhibited VEGF expression in tumor tissue. Angiopoietin-1 was expressed in tumor cells as well as endothelial cells in the stroma. Another interesting finding was that macrophages in HNSCC had an M2 “alternatively activated” phenotype and appeared to be the major source of endostatin in the stroma.

Conclusions:

Our novel results indicate that angiogenic factors are differentially expressed in the circulation and tumor tissue in HPV-positive and HPV-negative HNSCC and could potentially confer a more aggressive phenotype to HPV-negative tumors.