The impact of human papillomavirus (HPV) status is well recognized in head and neck squamous cell carcinoma (HNSCC) and results in improved prognosis and response to standard of care treatment in patients. However, the influence of HPV status on angiogenesis in HNSCC has yet to be comprehensively examined. Thus, we sought to dissect the HPV-angiogenesis link in HNSCC. We hypothesized HPV/p16 status influences the vascular phenotype and response to vascular-targeted therapy (VTT) in HNSCC. A combinatorial approach of molecular, immunohistochemical analysis (IHC) and photoacoustic imaging was performed in HPV+/p16+ and HPV-/p16- HNSCC tumors to assess the influence of HPV status on vascular phenotype and vascular function. Response to VTT was assessed utilizing dynamic-contrast enhanced magnetic resonance (DCE-MRI), IHC analysis and assessment of tumor growth inhibition post VTT. IHC analysis of HNSCC patient samples and PDXs revealed p16 status is associated with a stromal-based vascular phenotype. The stromal vessel phenotype in HPV+/p16+ PDXs is associated with more mature vasculature, greater tumor oygenation and enhanced response to radiation therapy. In contrast, HPV-/p16- PDXs exhibit significantly greater microvessel counts and more aggressive tumor growth in comparison to HPV+/p16+ PDXs. Acute-response to VTT was influenced by p16 status, showing HPV-/p16- PDXs exhibit significant anti-vascular activity post VTT. Long-term response to VTT was influenced by vascular phenotype, showing tumors exhibiting a tumor vessel phenotype demonstrated the greatest early and long-term response to VTT. In contrast, tumors classified as a stromal vessel phenotype did not exhibit tumor growth inhibition post treatment. To conclude, HPV+/p16+ tumors, associated with a stromal vessel phenotype are not suitable for vascular-targeted therapy.
|Commitee:||Hershberger, Pamela, Kozbor, Danuta, Spernyak, Joseph|
|School:||State University of New York at Buffalo|
|School Location:||United States -- New York|
|Source:||DAI-B 78/07(E), Dissertation Abstracts International|
|Keywords:||HNSCC, HPV-/p16- HNSCC tumors, HPV/p16 status, Vascular-targeted therapy|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be