Single-cell transcriptomic analysis of HPV-related multiphenotypic sinonasal carcinoma uncovers MYB-HPV association

Avishai Wizel; Matthew D.A. Spence; Michael Mints; William Britton; Ogoegbunam Okolo; Victoria Yu; Isabel Cioffi; Salvatore Caruana; Scott H. Troob; William C. Faquin; Derrick T. Lin; Itay Tirosh; Sidharth V. Puram; Anuraag S. Parikh; Yotam Drier

doi:10.1038/s41698-025-01164-5

Single-cell transcriptomic analysis of HPV-related multiphenotypic sinonasal carcinoma uncovers MYB-HPV association

Avishai Wizel
, Matthew D.A. Spence
, Michael Mints
, William Britton
, Ogoegbunam Okolo
, Victoria Yu
, Isabel Cioffi
, Salvatore Caruana
, Scott H. Troob
, William C. Faquin
, Derrick T. Lin
, Itay Tirosh
, Sidharth V. Puram
, Anuraag S. Parikh^*
, Yotam Drier^*

^*Corresponding author for this work

Department of Immunology and Cancer Research

Research output: Contribution to journal › Article › peer-review

Abstract

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a rare tumor that morphologically resembles high-grade adenoid cystic carcinoma (ACC) but exhibits indolent clinical behavior. Both demonstrate MYB proto-oncogene upregulation, though HMSC lacks the MYB translocation characteristic of ACC. We performed single-cell RNA sequencing on an HMSC tumor and compared expression patterns with published ACC and oropharyngeal squamous cell carcinoma (OPSCC) datasets. Malignant HMSC cells clustered separately from ACC and lacked bicellular luminal and myoepithelial differentiation. A greater proportion of HMSC cells expressing HPV-related genes (HPVon) expressed MYB (83% vs. 62%, p = 0.022) and MYB targets (p = 6.4 × 10⁻⁶), supporting an HPV-MYB association. Validation in HPV + OPSCC revealed MYB upregulation in HPVon cells from 7/10 tumors (p < 0.05). A 264-gene signature from HPVon HMSC cells correlated with worse prognosis in HPV + OPSCC (p < 0.003), suggesting an alternate role for HPV. Further validation of the HPV-MYB association and gene signature may improve therapeutic strategies in HPV-related malignancies.

Original language	English
Article number	378
Journal	npj Precision Oncology
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41698-025-01164-5
State	Published - Dec 2025

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© The Author(s) 2025.

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Wizel, A., Spence, M. D. A., Mints, M., Britton, W., Okolo, O., Yu, V., Cioffi, I., Caruana, S., Troob, S. H., Faquin, W. C., Lin, D. T., Tirosh, I., Puram, S. V., Parikh, A. S., & Drier, Y. (2025). Single-cell transcriptomic analysis of HPV-related multiphenotypic sinonasal carcinoma uncovers MYB-HPV association. npj Precision Oncology, 9(1), Article 378. https://doi.org/10.1038/s41698-025-01164-5

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title = "Single-cell transcriptomic analysis of HPV-related multiphenotypic sinonasal carcinoma uncovers MYB-HPV association",

abstract = "Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a rare tumor that morphologically resembles high-grade adenoid cystic carcinoma (ACC) but exhibits indolent clinical behavior. Both demonstrate MYB proto-oncogene upregulation, though HMSC lacks the MYB translocation characteristic of ACC. We performed single-cell RNA sequencing on an HMSC tumor and compared expression patterns with published ACC and oropharyngeal squamous cell carcinoma (OPSCC) datasets. Malignant HMSC cells clustered separately from ACC and lacked bicellular luminal and myoepithelial differentiation. A greater proportion of HMSC cells expressing HPV-related genes (HPVon) expressed MYB (83\% vs. 62\%, p = 0.022) and MYB targets (p = 6.4 × 10−6), supporting an HPV-MYB association. Validation in HPV + OPSCC revealed MYB upregulation in HPVon cells from 7/10 tumors (p < 0.05). A 264-gene signature from HPVon HMSC cells correlated with worse prognosis in HPV + OPSCC (p < 0.003), suggesting an alternate role for HPV. Further validation of the HPV-MYB association and gene signature may improve therapeutic strategies in HPV-related malignancies.",

author = "Avishai Wizel and Spence, \{Matthew D.A.\} and Michael Mints and William Britton and Ogoegbunam Okolo and Victoria Yu and Isabel Cioffi and Salvatore Caruana and Troob, \{Scott H.\} and Faquin, \{William C.\} and Lin, \{Derrick T.\} and Itay Tirosh and Puram, \{Sidharth V.\} and Parikh, \{Anuraag S.\} and Yotam Drier",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

doi = "10.1038/s41698-025-01164-5",

language = "אנגלית",

volume = "9",

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Wizel, A, Spence, MDA, Mints, M, Britton, W, Okolo, O, Yu, V, Cioffi, I, Caruana, S, Troob, SH, Faquin, WC, Lin, DT, Tirosh, I, Puram, SV, Parikh, AS & Drier, Y 2025, 'Single-cell transcriptomic analysis of HPV-related multiphenotypic sinonasal carcinoma uncovers MYB-HPV association', npj Precision Oncology, vol. 9, no. 1, 378. https://doi.org/10.1038/s41698-025-01164-5

TY - JOUR

T1 - Single-cell transcriptomic analysis of HPV-related multiphenotypic sinonasal carcinoma uncovers MYB-HPV association

AU - Wizel, Avishai

AU - Spence, Matthew D.A.

AU - Mints, Michael

AU - Britton, William

AU - Okolo, Ogoegbunam

AU - Yu, Victoria

AU - Cioffi, Isabel

AU - Caruana, Salvatore

AU - Troob, Scott H.

AU - Faquin, William C.

AU - Lin, Derrick T.

AU - Tirosh, Itay

AU - Puram, Sidharth V.

AU - Parikh, Anuraag S.

AU - Drier, Yotam

PY - 2025/12

Y1 - 2025/12

N2 - Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a rare tumor that morphologically resembles high-grade adenoid cystic carcinoma (ACC) but exhibits indolent clinical behavior. Both demonstrate MYB proto-oncogene upregulation, though HMSC lacks the MYB translocation characteristic of ACC. We performed single-cell RNA sequencing on an HMSC tumor and compared expression patterns with published ACC and oropharyngeal squamous cell carcinoma (OPSCC) datasets. Malignant HMSC cells clustered separately from ACC and lacked bicellular luminal and myoepithelial differentiation. A greater proportion of HMSC cells expressing HPV-related genes (HPVon) expressed MYB (83% vs. 62%, p = 0.022) and MYB targets (p = 6.4 × 10−6), supporting an HPV-MYB association. Validation in HPV + OPSCC revealed MYB upregulation in HPVon cells from 7/10 tumors (p < 0.05). A 264-gene signature from HPVon HMSC cells correlated with worse prognosis in HPV + OPSCC (p < 0.003), suggesting an alternate role for HPV. Further validation of the HPV-MYB association and gene signature may improve therapeutic strategies in HPV-related malignancies.

AB - Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a rare tumor that morphologically resembles high-grade adenoid cystic carcinoma (ACC) but exhibits indolent clinical behavior. Both demonstrate MYB proto-oncogene upregulation, though HMSC lacks the MYB translocation characteristic of ACC. We performed single-cell RNA sequencing on an HMSC tumor and compared expression patterns with published ACC and oropharyngeal squamous cell carcinoma (OPSCC) datasets. Malignant HMSC cells clustered separately from ACC and lacked bicellular luminal and myoepithelial differentiation. A greater proportion of HMSC cells expressing HPV-related genes (HPVon) expressed MYB (83% vs. 62%, p = 0.022) and MYB targets (p = 6.4 × 10−6), supporting an HPV-MYB association. Validation in HPV + OPSCC revealed MYB upregulation in HPVon cells from 7/10 tumors (p < 0.05). A 264-gene signature from HPVon HMSC cells correlated with worse prognosis in HPV + OPSCC (p < 0.003), suggesting an alternate role for HPV. Further validation of the HPV-MYB association and gene signature may improve therapeutic strategies in HPV-related malignancies.

UR - https://www.scopus.com/pages/publications/105022796155

U2 - 10.1038/s41698-025-01164-5

DO - 10.1038/s41698-025-01164-5

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C2 - 41286405

AN - SCOPUS:105022796155

SN - 2397-768X

VL - 9

JO - npj Precision Oncology

JF - npj Precision Oncology

IS - 1

M1 - 378

ER -

Single-cell transcriptomic analysis of HPV-related multiphenotypic sinonasal carcinoma uncovers MYB-HPV association

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