Intratumoral spatiotemporal heterogeneity of HPV status in HPV-associated oropharyngeal squamous cell carcinoma with clinical record

ABSTRACT: Heterogeneity in HPV status within HPV-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) has gained attention, but the origin and relevance of HPV-absent cancer cells remain unclear. Among 83 OPSCCs, including 48 HPV-OPSCCs, seven showed spatial HPV heterogeneity. Using HPV-DNA in situ hybridization, histomorphology, immunohistochemistry, and spatial transcriptomics, we revealed that HPV-absent subsets differentiate from initial HPV-positive cells, forming distinct lineages. HPV-OPSCC was associated with p16 expression, with HPV-absent clones showing robust p16 expression and poorly differentiated histology. Despite these aggressive features, prognosis was comparable to HPV-homogeneous tumors, likely due to tumor microenvironment differences. HPV-absent clones exhibited increased interferon signaling, hypoxia signaling, and cytotoxic lymphocyte infiltration, indicating a loss of antiviral immune evasion. Conversely, HPV-positive clones were linked to FGFR3 ligand-receptor signaling. This study highlights the emergence, evolution, and microenvironmental impact of HPV-absent clones in HPV-OPSCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE289363 | GEO | 2026/05/20

REPOSITORIES: GEO