HPV-status and its correlation to the expression of VEGFR2 in cancer cells and in blood vessels of OPSCC

Introduction:

Up to 50% of oropharyngeal squamous cell carcinoma (OPSCC) is associated with Human Papillomavirus (HPV) type 16 and it is known that HPV-positive and HPV-negative OPSCC exhibit different mutation patterns and expression signatures. Vascular endothelial growth factor receptor 2 (VEGFR2) regulates tumor angiogenesis. However, the effect of HPV-Infection on VEGFR2 expression in correlation to tumor angiogenesis in OPSCC is unknown.

Methods:

Paraffin sections of OPSCC samples (n = 46) with known HPV-status were incubated with VEGFR2 immunohistochemically. The colocalization of VEGFR2 with p16 and p53 in tumor cells and with CD31 in blood vessels was analyzed with double immunostaining. The number of VEGFR2-stained blood vessels and staining intensity of VEGFR2 in tumor cells were quantified by QuPath bioimage software. Results were correlated with clinicopathological data.

Results:

VEGFR2 expression was detected in numerous blood vessels of tumor regions as well as in tumor cells. Our statistical analysis showed significant differences in staining intensities between HPV-positive and -negative tumor cells (p = 0.0103). HPV-infection induces a significant downregulation of VEGFR2 in cancer cells compared to HPV-negative OPSCC. No significant differences in the number of VEGFR2-positive capillaries between HPV-negative and HPV-positive OPSCC were observed.

Conclusion:

We conclude that an increase of VEGFR2 expression in tumor cells is correlated to HPV-status. However, in the capillaries of OPSCC, vessel density is not affected by HPV infection. The high number of VEGFR2-positive capillaries in OPSCC is not a direct consequence of altered VEGFR2 expression in tumor cells. In the tumor milieu, the effects of HPV in OPSCC are regulated in a cell-specific manner.

Publication History

Publication Date:
23 April 2019 (online)