{
  "abstract": "Viral integration is common in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC), but its structural and clinical significance remains unclear. We integrated targeted capture sequencing of 197 HPV+ OPSCCs with long-read nanopore sequencing of 17 tumors and models to characterize HPV-host rearrangements. We developed a novel quantitative informatics framework that classifies integration structures as Type1 (simple, single/low-copy) or Type2 (clustered, high-copy, rearranged). HPV integration occurred in 83% of tumors, with recurrent hotspots including TP63, MYC, CD274, TRAF2, and KMT2C. Type2 events were enriched for HPV E2 disruption, focal human amplifications, preferential transcription, and noncanonical HPV-host RNA fusion isoforms. Type2 tumors showed increased HPV oncogene expression and activation of MYC, NF-{kappa}B/TNF, PI3K-AKT-mTOR, Hippo/YAP-TAZ, and epithelial stemness programs. Multi-region and longitudinal analyses revealed intratumoral heterogeneity and clonal selection of Type2 architectures during progression, supporting integration structure as a potential marker of aggressive behavior and risk stratification.",
  "abstract_shown": true,
  "affiliations": [
    "University of Michigan"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 29,
  "authors": [
    {
      "name": "W. Gu"
    },
    {
      "name": "A. D. Bhangale"
    },
    {
      "name": "X. Du"
    },
    {
      "name": "X. Deng"
    },
    {
      "name": "E. U. Gensterblum-Miller"
    },
    {
      "name": "J. Currie"
    },
    {
      "name": "C. V. Brummel"
    },
    {
      "name": "V. Nyabashi"
    },
    {
      "name": "M. Buchakjian"
    },
    {
      "name": "K. A. Casper"
    },
    {
      "name": "S. E. Chinn"
    },
    {
      "name": "D. Forner"
    },
    {
      "name": "K. M. Malloy"
    },
    {
      "name": "M. L. Mierzwa"
    },
    {
      "name": "M. E. Prince"
    },
    {
      "name": "J. L. Shah"
    },
    {
      "name": "A. G. Shuman"
    },
    {
      "name": "C. L. Stucken"
    },
    {
      "name": "P. L. Swiecicki"
    },
    {
      "name": "F. P. Worden"
    },
    {
      "name": "P. Yalamanchi"
    },
    {
      "name": "J. B. McHugh"
    },
    {
      "name": "K. A. Kuhs"
    },
    {
      "name": "A. P. Boyle"
    },
    {
      "name": "H. Jiang"
    },
    {
      "name": "M. E. Neal"
    },
    {
      "name": "M. E. Spector"
    },
    {
      "name": "R. E. Mills"
    },
    {
      "affs": [
        0
      ],
      "name": "C. J. Brenner"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5z1sntjt2vxpe.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.03.756294",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.03.756294v1.full",
  "id": "5z1sntjt2vxpe",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.03.756294v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "2733|Head and Neck Cancer Studies"
    ]
  ],
  "openalex": "W7221449293",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.03.756294v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5z1sntjt2vxpe.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:02Z",
      "native_id": "10.64898/2026.10.03.756294",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.03.756294v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Spatiotemporal Heterogeneity of HPV Integration Architectures Drive Oncogenic Features of Oropharyngeal Cancer",
  "title_text": "Spatiotemporal Heterogeneity of HPV Integration Architectures Drive Oncogenic Features of Oropharyngeal Cancer",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:02Z",
  "url": "https://research.draconitic.com/paper/5z1sntjt2vxpe",
  "venue": "bioRxiv",
  "versions": []
}