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.
from sddb import Catalog
cohort = Catalog().collection("geo-gse289363")
cohort.members # the 3 datasets as a table
print(cohort.licenses()) # check the terms before you download
sdatas = cohort.to_dict() # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/")Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.
import lamindb as ln
db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse289363")
coll.ordered_artifacts.to_dataframe() # the 3 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse289363 --dest data/Licenses: 3 NCBI GEO policy
@article{Ahn_2026,
title = {Intratumoral spatiotemporal heterogeneity of HPV DNA status in HPV-associated oropharyngeal squamous cell carcinoma with clinical record},
volume = {24},
ISSN = {1479-5876},
url = {http://dx.doi.org/10.1186/s12967-026-08082-5},
DOI = {10.1186/s12967-026-08082-5},
number = {1},
journal = {Journal of Translational Medicine},
publisher = {Springer Science and Business Media LLC},
author = {Ahn, Bokyung and Park, Chae Won and Song, Joon Seon and Lee, Hee-Jin and Kim, Wonkyung and Lee, Yoon Se and Jung, Young Ho and Choi, Seung-Ho and Nam, Soon Yuhl and Kim, Sang Yoon and Oh, Ji-Hye and Kang, Young Gwang and Oh, Da Eun and Sung, Chang Ohk and Cho, Kyung-Ja},
year = {2026},
month = Apr
}