Differences in gene expression between high‐grade dysplasia and invasive HPV+ and HPV− tonsillar and base of tongue cancer. (27th August 2019) - Haeggblom, Linnea
Abstract: Background: Human papillomavirus (HPV) is a causative agent for tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC), as well as for cervical cancer. Premalignant stages in cervical cancer have been studied extensively, while little is known about premalignant stages in TSCC/BOTSCC and the role of HPV. Here we analyzed differences in gene and protein expression between high‐grade dysplasia and invasive cancer in both HPV‐positive (HPV + ) and HPV‐negative (HPV − ) TSCC/BOTSCC. Methods: High‐grade dysplasia and invasive carcinoma were laser microdissected from HPV + and HPV − TSCC/BOTSCC tumor sections. Differential gene expression was studied utilizing nanoString RNA‐panels and genes of interest were validated on the protein level by immunohistochemistry. Results: Forty genes in the HPV + tumors showed significantly different expression between high‐grade dysplasia and invasive cancer and 33 genes in the HPV − tumors. Five out of the nine most significant pathways showed similar increased activity in invasive cancer as compared to high‐grade dysplasia in both HPV + and HPV − tumors. Lastly, significant differences in protein expression was confirmed for SPARC, psoriasin, type I collagen and galectin‐1 in both HPV + and HPV − tumors. Conclusions: This is to our knowledge the first study disclosing differences and similarities in gene expression between dysplastic and invasive HPV + and HPV − TSCC/BOTSCC. Abstract : It is debated if high‐grade dysplasia exists in HPV+ TSCC/BOTSCC, there is also a need for pathological invasion markers in HNSCC. Here we present similarities between HPV+ and HPV‐ high‐grade dysplasia, suggesting HPV+ high‐grade dysplasia is an entity. We also identify possible invasion markers in HNSCC.