Head and Neck Cancer Stem Cells: The Effect of HPV

Abstract

Objective: To determine the relative sensitivity to cisplatin of cancer stem cells (CSC) and if behavior and proportion of CSC in cell lines is affected by HPV. We determined the effect of HPV oncogenes on the tumorigenicity of naturally infected, HPV-negative, and viral oncogene transduced human HNSCC cells in mice.

Method: Using naturally infected HPV+ and HPV– cell lines, we isolated CSC by flow cytometry with ALDH. Chemoresistence was determined using colony formation assays. Two HPV– cell lines underwent lentiviral transduction of E6/E7. Native and E6/E7 transduced cells were compared for lung colonization after tail vein injection in NOD/SCID mice.

Results: HPV+ CSCs were more resistant to cisplatin than non-CSCs. There were no differences in chemoresistance between HPV+ and HPV– cells. HPV– cells yielded low colony formation after cell sorting across all groups. However, after transduction with E6/E7, increased colony formation was observed in both CSC and non-CSC for these same cells. Results from tail vein injections yielded no differences in development of lung lesions between E6/E7 transduced cells vs non-E6/E7 cells.

Conclusion: CSC are more resistant to cisplatin than non-CSC. Chemotherapy may shrink tumor bulk by eliminating non-CSC, but CSC have inherent mechanisms that allow evasion. HPV does not affect CSC in the face of therapy, suggesting that other factors, possibly immune regulated, explain the observed better outcomes in HPV+ cancer patients.