Cellular states are coupled to genomic and viral heterogeneity in HPV-related oropharyngeal carcinoma

Sidharth V. Puram, Michael Mints, Ananya Pal, Zongtai Qi, Ashley Reeb, Kyla Gelev, Thomas F. Barrett, Sophie Gerndt, Ping Liu, Anuraag S. Parikh, Salma Ramadan, Travis Law, Edmund A. Mroz, James W. Rocco, Doug Adkins, Wade L. Thorstad, Hiram A. Gay, Li Ding, Randal C. Paniello, Patrik PipkornRyan S. Jackson, Xiaowei Wang, Angela Mazul, Rebecca Chernock, Jose P. Zevallos, Jessica Silva-Fisher, Itay Tirosh

Research output: Contribution to journalArticlepeer-review


Head and neck squamous cell carcinoma (HNSCC) includes a subset of cancers driven by human papillomavirus (HPV). Here we use single-cell RNA-seq to profile both HPV-positive and HPV-negative oropharyngeal tumors, uncovering a high level of cellular diversity within and between tumors. First, we detect diverse chromosomal aberrations within individual tumors, suggesting genomic instability and enabling the identification of malignant cells even at pathologically negative margins. Second, we uncover diversity with respect to HNSCC subtypes and other cellular states such as the cell cycle, senescence and epithelial-mesenchymal transitions. Third, we find heterogeneity in viral gene expression within HPV-positive tumors. HPV expression is lost or repressed in a subset of cells, which are associated with a decrease in HPV-associated cell cycle phenotypes, decreased response to treatment, increased invasion and poor prognosis. These findings suggest that HPV expression diversity must be considered during diagnosis and treatment of HPV-positive tumors, with important prognostic ramifications.

Original languageEnglish
Pages (from-to)640-650
Number of pages11
JournalNature Genetics
Issue number4
StatePublished - Apr 2023

All Science Journal Classification (ASJC) codes

  • Genetics


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