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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.

Author information

1
Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
2
Department of Clinical Pathology, Karolinska University Hospital, Stockholm, Sweden.
3
Department of Microbiology, University of Medicine and Pharmacy Grigore T. Popa Iasi, Iasi, Romania.

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.

KEYWORDS:

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

PMID:
31454186
DOI:
10.1002/cam4.2450
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