ArticleJournal of translational medicine2026
Intratumoral spatiotemporal heterogeneity of HPV DNA status in HPV-associated oropharyngeal squamous cell carcinoma with clinical record.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- HPV-Associated Oropharyngeal Squamous Cell Carcinoma and Persistent Oral High-Risk HPV Detection: A Narrative Review of Longitudinal Assessment, Diagnostic Evaluation, and Surveillance.International journal of molecular sciences · 2026Review
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Authors and funding
15 authors.
Funding
Abstract
backgroundRecently, the heterogeneity of human papillomavirus (HPV) status within HPV-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) has garnered substantial attention. However, the origin and relevance of a subset of cancer cells with HPV-loss remain largely unknown.
methodsWe encountered seven HPV-OPSCCs with spatial heterogeneity identified by HPV-DNA in situ hybridization among 83 OPSCCs, including 48 HPV-OPSCCs. We analyzed the characteristics of HPV-loss and HPV-positive cancer cells using histomorphology and immunohistochemistry. Spatial transcriptomic profiling was performed to investigate the evolutionary dynamics and pathway alterations associated with the emergence of HPV-loss tumor cells, as well as the corresponding changes in the tumor microenvironment. Additionally, we evaluated the clinical prognosis of OPSCCs exhibiting intratumoral HPV-DNA heterogeneity.
resultsWe demonstrated that HPV-loss subsets originate from HPV-positive cancer cells and diverge into distinct lineages during spatiotemporal evolution. This transition was associated with hypoxia and PI3K/AKT/mTOR signaling. Although HPV-loss clones showed more aggressive features such as poor differentiation and strong p16 expression, the overall prognosis of patients with HPV-DNA spatial heterogeneity was comparable to those with homogeneous HPV status. This may be due to increased interferon signaling and elevated cytotoxic lymphocyte infiltration in HPV-loss clones, suggesting a loss of immune evasion. In contrast, HPV-positive clones retained immune evasion mechanisms, potentially mediated by Fibroblast Growth Factor Receptor 3 signaling.
conclusionsWe identified the emergence of HPV-loss clones in HPV-OPSCC and uncovered their spatiotemporal evolution characteristics, as well as their impact on the tumor microenvironment.
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