Human and viral whole genome sequencing identify HPV and APOBEC as oncogenic drivers in sinonasal squamous cell

Insights

Human papillomavirus (HPV) drives sinonasal squamous cell carcinoma (SNSCC) evolution, particularly through lesser-studied strains. Understanding these HPV-human interactions is crucial for advancing SNSCC diagnostics and treatment strategies.

Area of Science:

  • Oncology
  • Virology
  • Genomics

Background:

  • Sinonasal squamous cell carcinoma (SNSCC) is an aggressive head and neck cancer with limited therapeutic progress.
  • While historically linked to environmental factors, SNSCC shows incidental association with human papillomavirus (HPV).
  • HPV is a known driver in oropharyngeal cancers, but its role in SNSCC is not fully understood.

Purpose of the Study:

  • To investigate the genomic footprint of HPV in SNSCC.
  • To identify the specific HPV strains involved in SNSCC oncogenesis.
  • To elucidate the mechanisms of host-virus interactions in SNSCC tumor evolution.

Main Methods:

  • Paired host and viral whole-genome sequencing (WGS) of SNSCC tumors.
  • Analysis of viral integration patterns and host genomic alterations.
  • Identification of specific HPV strains and their association with extrachromosomal DNA (ecDNA).

Main Results:

  • HPV was confirmed as a primary oncogenic driver in SNSCC.
  • Lesser-studied HPV strains (e.g., HPV45, 51, 39) were identified as driver infections.
  • HPV integration into ecDNA and APOBEC mutagenesis were key mechanisms in tumor evolution.

Conclusions:

  • HPV, including noncanonical strains, plays a significant role in SNSCC carcinogenesis.
  • HPV-human ecDNA amplicons are critical mediators of viral oncogenesis in SNSCC.
  • Current HPV diagnostic panels should be expanded to include lesser-studied strains for comprehensive SNSCC detection.

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