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RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma
Published on: March 11, 2014
Human and viral whole genome sequencing identify HPV and APOBEC as oncogenic drivers in sinonasal squamous cell
Abstract:
Sinonasal squamous cell carcinoma (SNSCC) is an aggressive head and neck cancer of the sinonasal cavity which has not benefitted from therapeutic advances over decades 1 . Though historically attributed to inhaled carcinogens such as hardwood dust and tobacco smoking 2 , SNSCC is incidentally associated with human papillomavirus (HPV) 3,4 . Importantly, HPV is the primary oncogenic driver of >80% of anatomically adjacent oropharyngeal cancers 5 . While viral status drives clinical staging and treatment guidelines in these malignancies 6,7 , the potentially oncogenic consequences and prognostic value of host-virus interactions in SNSCC remain incompletely defined. Here, through paired host and viral whole-genome sequencing (WGS), we map the genomic footprint of HPV in SNSCC. Strikingly, lesser studied strains such as HPV45, 51, and 39 constitute driver infections in this rare but clinically credentialed cancer, where extrachromosomal DNA (ecDNA)-associated viral integration and APOBEC mutagenesis are shown to underpin somatic tumor evolution.
Statement Of Significance:
Paired host viral and whole-genome sequencing of SNSCC nominates HPV as a primary oncogenic driver of SNSCC. HPV-human ecDNA amplicons harboring noncanonical strains such as HPV45, 51 mediate viral carcinogenesis. Routine clinical diagnostic HPV panels should be expanded to capture the activity of lesser studied strains.
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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