Abstract

Purpose Head and neck cancers (HNC) are aggressive tumours. Expression of Human Papilloma Virus (HPV)-derived protein p16 in HNC is known to correlate with a better prognosis than p16-negative tumours. Angiogenesis is an important factor in tumour progression. Our aim was to dissect the impact of HPV on angiogenic factors in HNC. Methods 18 newly diagnosed HNC patients and controls were analysed in this study. A panel of 11 pro- and anti-angiogenic factors was quantified in serum samples of HNC patients and controls using multiplex ELISA and correlated to the p16 expression in the tumour tissue. Tumour tissue was tested using immunohistochemistry for the expression of angiogenic factors and co-localisation performed to identify the predominant cellular source of angiogenic factors. Results All patients had higher circulating levels of the antiangiogenic factor endostatin compared to healthy donors. Interestingly, higher levels of the proangiogenic factors angiopoetin, placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) were noted in patients who did not express p16 compared to those who did. Tumour associated macrophages appear to be a major cellular source of these angiogenic factors and work is underway to analyse the expression of angiogenic factors in HPV-positive and negative tumour tissue. Conclusions HNC patients that lack p16 expression have a different pattern of angiogenic factors with increased proangiogenic factors angiopoietin, PlGF and VEGF. This may confer a more aggressive phenotype to p16-negative tumours. Better understanding of the mechanisms by which HPV induces changes in tumour angiogenesis may guide the development of novel therapeutic targets.

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