Detection of Human Papillomavirus Integration in Brain Metastases from Oropharyngeal Tumors by Targeted Sequencing

McEllin, Brian; Searle, Brian C.; DePledge, Lisa; Sun, George; Cobbs, Charles; Karimi, Mohsen

doi:10.3390/v13081536

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Detection of Human Papillomavirus Integration in Brain Metastases from Oropharyngeal Tumors by Targeted Sequencing

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The Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, WA 98122, USA

Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA

Author to whom correspondence should be addressed.

Academic Editors: Sherif T. S. Hassan and Subhash C. Verma

Viruses 2021, 13(8), 1536; https://doi.org/10.3390/v13081536

Received: 25 May 2021 / Revised: 22 July 2021 / Accepted: 28 July 2021 / Published: 3 August 2021

(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)

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Abstract

Human papillomavirus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC) are known to have differential phenotypes, including the incidence and location of metastases. HPV positive (HPV+) HNSCC are more likely to metastasize to distant sites, such as the lung, brain, and skin. Among these locations, metastasis to the brain is a rare event, and little is known about specific risk factors for this phenotype. In this report, we describe two patients who developed brain metastases from HNSCC. Both patient tumors had p16^INK4a overexpression, suggesting these tumors were HPV+. This was confirmed after PCR, in situ hybridization, and mass spectrometry detected the presence of HPV type 16 (HPV16) DNA, RNA and protein. To further characterize the presence of HPV16, we used a target enrichment strategy on tumor DNA and RNA to isolate the viral sequences from the brain metastases. Analysis by targeted next generation sequencing revealed that both tumors had the HPV genome integrated into the host genome at known hotspots, 8q24.21 and 14q24.1. Applying a similar target enrichment strategy to a larger cohort of HPV+ HNSCC brain metastases could help to identify biomarkers that can predict metastasis and/or identify novel therapeutic options. View Full-Text

Keywords: brain metastasis; HPV; HNSCC; OPSCC; targeted sequencing; DNA target enrichment; data-independent acquisition; proteomics

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McEllin, B.; Searle, B.C.; DePledge, L.; Sun, G.; Cobbs, C.; Karimi, M. Detection of Human Papillomavirus Integration in Brain Metastases from Oropharyngeal Tumors by Targeted Sequencing. Viruses 2021, 13, 1536. https://doi.org/10.3390/v13081536

AMA Style

McEllin B, Searle BC, DePledge L, Sun G, Cobbs C, Karimi M. Detection of Human Papillomavirus Integration in Brain Metastases from Oropharyngeal Tumors by Targeted Sequencing. Viruses. 2021; 13(8):1536. https://doi.org/10.3390/v13081536

Chicago/Turabian Style

McEllin, Brian, Brian C. Searle, Lisa DePledge, George Sun, Charles Cobbs, and Mohsen Karimi. 2021. "Detection of Human Papillomavirus Integration in Brain Metastases from Oropharyngeal Tumors by Targeted Sequencing" Viruses 13, no. 8: 1536. https://doi.org/10.3390/v13081536

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Detection of Human Papillomavirus Integration in Brain Metastases from Oropharyngeal Tumors by Targeted Sequencing

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