Dissertation/Thesis Abstract

The influence of p16 status on vascular phenotype and response to vascular-targeted therapy in head and neck squamous cell carcinoma
by Folaron, Margaret, Ph.D., State University of New York at Buffalo, 2016, 180; 10255304
Abstract (Summary)

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.

Indexing (document details)
Advisor: Seshadri, Mukund
Commitee: Hershberger, Pamela, Kozbor, Danuta, Spernyak, Joseph
School: State University of New York at Buffalo
Department: Biophysics
School Location: United States -- New York
Source: DAI-B 78/07(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Biophysics
Keywords: HNSCC, HPV-/p16- HNSCC tumors, HPV/p16 status, Vascular-targeted therapy
Publication Number: 10255304
ISBN: 9781369593501
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