Evidence mapPaperPMID 41256339Full record

ArticleWorld journal of clinical cases2025

Rethinking p16, p53, and HPV in HNCSCC through lessons from glioblastoma subclonal evolution toward patient-centric N-of-1 single-cell RNA sequencing paradigm.

Henry Michael Lee, Shengwen Calvin Li

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In one paragraph

Article in World journal of clinical cases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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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.

2 · The registry

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3 · Its place in the literature

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No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

2 authors.

Henry Michael LeeDepartment of Neurology, University of California-Irvine School of Medicine, Orange, CA 92868, United States.
Shengwen Calvin LiDepartment of Neurology, University of California-Irvine School of Medicine, Orange, CA 92868, United States. sli@choc.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Head and neck cutaneous squamous cell carcinoma (HNCSCC) remains underexplored compared to oropharyngeal squamous cell carcinoma, particularly in relation to human papillomavirus (HPV) and molecular markers such as p16 and p53. While p16 is a well-established surrogate for HPV in oropharyngeal cancer, our review highlights its unreliable role in HNCSCC, where positivity is instead associated with recurrence and metastasis. Similarly, p53 illustrates a dual role - wild-type as a genomic safeguard, mutated as an oncogenic driver - complicating prognostication. Methodological considerations, including the limitations of immunohistochemistry for HPV detection, underscore the need for multi-method and molecular validation in future studies. Ultraviolet radiation is posited as a key modifier of p16 function, decoupling expression from tumor suppression. To contextualize these findings, we draw parallels to glioblastoma (GBM), where subclonal evolution, p53 dysfunction, and intratumoral heterogeneity drive relapse despite aggressive multimodal therapies. GBM exemplifies how bulk-level biomarker generalizations often obscure dynamic cellular ecosystems, reinforcing the necessity of single-cell and spatial approaches. Multi-omics integration - encompassing genome, transcriptome, proteome, and tumor microenvironment mapping - coupled with single-cell RNA sequencing and spatial transcriptomics, offers a path forward for resolving subclonal dynamics in both HNCSCC and GBM. These technologies provide the resolution needed to track tumor-immune-stromal co-evolution, identify therapy-resistant clones, and anticipate recurrence. We argue for a N-of-1, patient- and cell-centric paradigm that reframes biomarkers not as static surrogates but as dynamic readouts of cancer evolution across time and tissue contexts. Conceptually, we propose kinetic and microenvironmental frameworks (

Indexed as

GlioblastomaHead and neck cutaneous squamous cell carcinomaHuman papilloma virusN-of-1 paradigmp16p53Single-cell RNA sequencingSpatial transcriptomicsSubclonal evolutionUltraviolet radiation

Identifiers

PMID41256339
PMCPMC12620850

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.