Geographic variation in human papillomavirus–related oropharyngeal cancer:data from four multinational randomized trials

Background: There are variations in the proportions of head and neck cancers (HNC) caused by the Human Papillomavirus (HPV) between countries and regions. It is unclear if these are true variations or due to different study designs and assays.Methods: We tested FFPE diagnostic biopsies for p16 immunohistochemistry and HPV-DNA (by PCR and ISH) using validated protocols on samples from 801 HNC patients recruited prospectively between 2006 – 2011 in 4 RCTs. Results: 21% (170/801) showed both HPV-DNA and p16 positivity, detected almost exclusively in oropharyngeal cancer (OPC) (55%, 15/302); only 1%, (5/499) non-OPC were positive. HPV OPC differed between Western and Eastern Europe (37%, 155/422vs 6%, 8/144 p<0.0001) and between Western Europe and Asia (37% vs 2%, 4/217, p<0·0001). Other independent determinants of HPV positivity were tumour site and smoking. Conclusions: This is the first study to establish geographic variability as an independent risk factor in HPV OPC prevalence, with higher prevalence in Western Europe