Genotyping and Characterization of HPV Status, Hypoxia, and Radiosensitivity in 22 Head and Neck Cancer Cell Lines.

Eva-Leonne Göttgens,Paul N Span,Johan Bussink,William P J Leenders,Marleen Ansems

doi:10.3390/cancers13051069

Abstract

Simple SummaryCell lines are widely used for research, but even commonly used cell lines may not be well characterized, making validation of published data and generalizing the results to the clinic problematic. Here, we have established a head and neck squamous cell carcinomas (HNSCC) cell line database. We believe that these cell lines are suitable models to study HNSCC disease in vitro and in vivo and may provide a valuable tool for investigators wishing to study the relation between e.g., hypoxia and radiosensitivity in HNSCC.To study head and neck squamous cell carcinomas (HNSCC) in vitro, a large variety of HNSCC cell lines have been developed. Here, we characterize a panel of 22 HNSCC cell lines, thereby providing a tool for research into tumor-specific treatment options in HNSCC. Both human papillomavirus (HPV) positive and HPV negative tumor cell lines were collected from commercial and collaborative sources. Short tandem repeat profiling was used to confirm or characterize the identity of the cell lines. Targeted sequencing was performed using a standard pathology single molecule Molecular Inversion Probe panel to detect mutations for 23 tumor suppressors and oncogenes. HPV status, p16 status, radiosensitivity data, and hypoxia data are summarized from all cell lines. We detected HPV transcripts in five cell lines, all of which overexpressed p16. One HPV negative cell line was also p16 positive. We detected mutations in KIT (SCCNij185), PIK3CA (SCCNij185), and CDKN2A (UT-SCC-5 and UT-SCC-38). TP53 mutations were the most frequent, occurring in 16/22 cell lines. HPV infection and TP53 mutations were almost mutually exclusive, with the exception of 93-VU-147T. The cell lines exhibited a wide range of sensitivities towards hypoxia and irradiation. Here, we provide a description of a set of frequently used HNSCC cell lines with diverse characteristics as found in HNSCC patients.

Highlights

Head and neck squamous cell carcinomas (HNSCC) are a malignant disease occurring in the mucosal regions of the oral cavity, hypopharynx, oropharynx, larynx, and other sites in the upper respiratory tract
Treatment of HNSCC consists of a combination of surgery, platinum-based chemotherapy, radiotherapy, and—more recently—PD1 immune checkpoint inhibitors for recurrent HNSCC [2,3,4,5]
We demonstrated that UT-SCC-45 was infected with HPV33, and UPCI:SCC090, UPCI:SCC154, 93-VU-147T, and UM-SCC-47 were infected with HPV16, whereas we did not detect any human papillomavirus (HPV) in other HNSCC cell lines [21,41]

Summary

Introduction

Head and neck squamous cell carcinomas (HNSCC) are a malignant disease occurring in the mucosal regions of the oral cavity, hypopharynx, oropharynx, larynx, and other sites in the upper respiratory tract. It is a heterogeneous group of malignancies that, depending on disease type and location, has a relatively poor prognosis [1,2]. Five-year survival rates in oropharyngeal cancer are approximately 65% [1,2]. In oropharyngeal cancer, the prevalence of HPV infection is relatively high with up to 81.4% of the patients infected with the virus [6,7]. Several studies have shown that patients with HPV positive tumors, and—

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