Effect of PI3K Inhibition in HPV-Associated HNSCC

Trial Information

Effect of PI3K Inhibition in HPV-Associated HNSCC

OBJECTIVES:

- Analyze PIK3CA expression and mutation and p110α amplification and expression in tumor
tissue samples from patients with human papilloma virus positive (HPV+) and human
papilloma virus negative (HPV-) squamous cell carcinoma (SCC) of the oropharynx.

- Determine proliferation and survival after PI3K inhibition in HPV(+) and HPV(-)
oropharyngeal SCC cell lines and in HPV E6 and E7 expressing cells.

- Determine proliferation and survival after PI3K inhibition in short-term cultures of
tumor tissue samples from patients with HPV(+) and HPV(-) primary SCC of the
oropharynx.

OUTLINE: Previously collected tumor tissue samples are analyzed for HPV DNA by PCR
amplification and direct sequencing of PCR products; expression of E6 protein and relative
expression of PIK3CA by qRT-PCR; amplification of PIK3CA by Southern blotting; mutation of
PIK3CA; expression of p110α, phospho-AKT, total AKT, and FOXO1 by polyacrylamide gel
electrophoresis (PAGE) and immunoblotting; and the effect of PI3K inhibition on cell cycle
and apoptosis by flow cytometry. Pharmacological studies are performed on oropharyngeal
squamous cell carcinoma cell lines and short-term cultures and HPV E6 and E7 expressing
cells using LY 294002 in vitro to analyze response to PI3K inhibition. Results of response
to PI3K inhibition will be correlated with HPV status, PIK3CA expression, amplification, and
mutation, and p110α expression.

PROJECTED ACCRUAL: A total of 20 HPV(+) and 20 HPV(-) tumor tissue specimens from patients
will be accrued for this study.