Molecular patterns and mechanisms of tumorigenesis in HPV-associated and HPV-independent sinonasal squamous cell carcinoma

Fernando T. Zamuner, Sreenivasulu Gunti, Gabriel J. Starrett, Farhoud Faraji, Tiffany Toni, Anirudh Saraswathula, Kenny Vu, Anuj Gupta, Yan Zhang, Daniel L. Faden, Michael E. Bryan, Theresa Guo, Nicholas R. Rowan, Murugappan Ramanathan, Andrew P. Lane, Carole Fakhry, Gary L. Gallia, Clint T. Allen, Lisa M. Rooper and Nyall R. London ()
Additional contact information
Fernando T. Zamuner: Johns Hopkins University School of Medicine
Sreenivasulu Gunti: National Institutes of Health
Gabriel J. Starrett: National Institutes of Health
Farhoud Faraji: University of California San Diego Health
Tiffany Toni: Johns Hopkins University School of Medicine
Anirudh Saraswathula: Johns Hopkins University School of Medicine
Kenny Vu: National Institutes of Health
Anuj Gupta: School of Medicine
Yan Zhang: School of Medicine
Daniel L. Faden: Harvard Medical School
Michael E. Bryan: Harvard Medical School
Theresa Guo: University of California San Diego Health
Nicholas R. Rowan: Johns Hopkins University School of Medicine
Murugappan Ramanathan: Johns Hopkins University School of Medicine
Andrew P. Lane: Johns Hopkins University School of Medicine
Carole Fakhry: Johns Hopkins University School of Medicine
Gary L. Gallia: Johns Hopkins University School of Medicine
Clint T. Allen: National Institutes of Health
Lisa M. Rooper: Johns Hopkins University School of Medicine
Nyall R. London: Johns Hopkins University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Mechanisms of tumorigenesis in sinonasal squamous cell carcinoma (SNSCC) remain poorly understood due to its rarity. A subset of SNSCC is associated with human papillomavirus (HPV), but it is unclear whether HPV drives tumorigenesis or acts as a neutral bystander. Here, we show that HPV-associated SNSCC shares mutational patterns found in HPV-associated cervical and head and neck squamous cell carcinoma, including lack of TP53 mutations, hotspot mutations in PI3K and FGFR3, enrichment of APOBEC mutagenesis, viral integration at known hotspots, and frequent epigenetic regulator alterations. We identify HPV-associated SNSCC-specific recurrent mutations in KMT2C, UBXN11, AP3S1, MT-ND4, and MT-ND5, with KMT2D and FGFR3 mutations correlating with reduced overall survival. We establish an HPV-associated SNSCC cell line, showing that combinatorial small-molecule inhibition of YAP/TAZ and PI3K synergistically suppresses clonogenicity. Combining YAP/TAZ blockade with vertical PI3K inhibition may benefit HPV-associated SNSCC, whereas targeting MYC and horizontal inhibition of RAS/PI3K may suit HPV-independent SNSCC.

Date: 2025
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59409-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59409-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-59409-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().