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Cancer Med. 2019 Aug 27. doi: 10.1002/cam4.2450. [Epub ahead of print]

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

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Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
Department of Clinical Pathology, Karolinska University Hospital, Stockholm, Sweden.
Department of Microbiology, University of Medicine and Pharmacy Grigore T. Popa Iasi, Iasi, Romania.



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.


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.


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.


This is to our knowledge the first study disclosing differences and similarities in gene expression between dysplastic and invasive HPV+ and HPV- TSCC/BOTSCC.


base of tongue cancer; cancer in situ; cancer progression; high-grade dysplasia; human papillomavirus; invasive carcinoma; oropharyngeal cancer; premalignant stages; tonsillar cancer

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