Differences in gene expression between high-grade dysplasia and invasive HPV⁺ and HPV^- tonsillar and base of tongue cancer

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.