Human Papillomavirus Integration Strictly Correlates with Global Genome Instability in Head and Neck Cancer

Brandon Labarge, Max Hennessy, Lijun Zhang, David Goldrich, Scott Chartrand, Carson Purnell, Sage Wright, David Goldenberg, James R. Broach

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Human papillomavirus (HPV)-positive head and neck cancers, predominantly oropharyngeal squamous cell carcinoma (OPSCC), exhibit epidemiologic, clinical, and molecular characteristics distinct from those OPSCCs lacking HPV. We applied a combination of whole-genome sequencing and optical genome mapping to interrogate the genome structure of HPV-positive OPSCCs. We found that the virus had integrated in the host genome in two thirds of the tumors examined but resided solely extrachromosomally in the other third. Integration of the virus occurred at essentially random sites within the genome. Focal amplification of the virus and the genomic sequences surrounding it often occurred subsequent to integration, with the number of tandem repeats in the chromosome accounting for the increased copy number of the genome sequences flanking the site of integration. In all cases, viral integration correlated with pervasive genome-wide somatic alterations at sites distinct from that of viral integration and comprised multiple insertions, deletions, translocations, inversions, and point mutations. Few or no somatic mutations were present in tumors with only episomal HPV. Our data could be interpreted by positing that episomal HPV is captured in the host genome following an episode of global genome instability during tumor development. Viral integration correlated with higher grade tumors, which may be explained by the associated extensive mutation of the genome and suggests that HPV integration status may inform prognosis.

Original languageEnglish (US)
Pages (from-to)1420-1428
Number of pages9
JournalMolecular Cancer Research
Issue number9
StatePublished - Sep 2022

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Oncology
  • Cancer Research


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