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BMC Cancer
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Human Papillomavirus | Research article

A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin

Authors: Ola Forslund, Natsuki Sugiyama, Chengjun Wu, Naveen Ravi, Yuesheng Jin, Sabine Swoboda, Fredrik Andersson, Davit Bzhalava, Emilie Hultin, Kajsa Paulsson, Joakim Dillner, Stefan Schwartz, Johan Wennerberg, Lars Ekblad

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Human papillomavirus (HPV) is an established risk factor for oropharyngeal squamous cell carcinoma (OSCC). The aim was to establish cell lines from HPV-positive tonsil carcinomas to be used for treatment development.

Methods

Fresh samples from 23 HPV-positive tonsil carcinomas were cultivated in vitro. The established cell line was analyzed for viral characteristics, cell karyotype, TP53 status, and growth capabilities in nude mice. In vitro studies of sensitivities to radiation, cisplatin and cetuximab were performed.

Results

After 19 months (eight passages), one cell line, LU-HNSCC-26, was established in vitro and also grew as xenografts. The tumor was from a 48 year old non-smoking man with non-keratinizing, p16 positive tonsil OSCC, stage T2N0M0 with HPV16. It contained 19.5 (CV% 3.7) HPV16 copies/cell (passage 8). The complete HPV16 genome sequence was obtained. Episomal HPV16 was present with an E2/E7 ratio of 1.1 (CV% 2.6). In addition, HPV16 mRNA specific for the intact E2 gene was detected. The viral expression manifested 1.0 (CV% 0.1) E7 mRNA copies per HPV16 genome. The karyotype was determined and the cell line demonstrated wild type TP53. The ID50 for radiation was 0.90 Gy and the IC50 for cisplatin was 0.99 μmol/L. The cell line was inhibited to a maximum of 18% by cetuximab.

Conclusions

We established an in vitro tonsil carcinoma cell line containing episomal HPV16. This is an important step towards efficient treatment development.
Appendix
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Metadata
Title
A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin
Authors
Ola Forslund
Natsuki Sugiyama
Chengjun Wu
Naveen Ravi
Yuesheng Jin
Sabine Swoboda
Fredrik Andersson
Davit Bzhalava
Emilie Hultin
Kajsa Paulsson
Joakim Dillner
Stefan Schwartz
Johan Wennerberg
Lars Ekblad
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5469-8

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