Evidence map›Paper›PMID 40499462›Full record

ArticleESMO open2025

Squamous cell carcinoma of unknown primary (SCCUP): a genomic landscape study.

H R Robinson, S Lakritz, D C Pavlick, S L Davis, C H Lieu, C J Eule, L S Graham, P E Spiess, R Li, A M Kamat and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Observational
  3. Article
  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

H R RobinsonDepartment of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, USA. Electronic address: hannah.r.robinson@cuanschutz.edu.
S LakritzDepartment of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, USA.
D C PavlickFoundation Medicine Inc., Cambridge, USA.
S L DavisDepartment of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, USA.
C H LieuDepartment of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, USA.
C J EuleDepartment of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, USA.
L S GrahamDepartment of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, USA.
P E SpiessMoffitt Cancer Center, Tampa, USA.
R LiMoffitt Cancer Center, Tampa, USA.
A M KamatMD Anderson Cancer Center, Houston, USA.
P GrivasFred Hutch Cancer Center & University of Washington, Seattle, USA.
J M JacobState University of New York Upstate Medical University, Syracuse, USA.
G BratslavskyState University of New York Upstate Medical University, Syracuse, USA.
A BasnetState University of New York Upstate Medical University, Syracuse, USA.
K A WongFoundation Medicine Inc., Cambridge, USA.
D I LinFoundation Medicine Inc., Cambridge, USA.
A NecchiSan Raffaele Hospital and Scientific Institute, Milan, Italy.
J S RossFoundation Medicine Inc., Cambridge, USA; State University of New York Upstate Medical University, Syracuse, USA.
E T LamDepartment of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, USA.

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
NCI NIH HHS P30 CA046934
6 · The paper itself

Abstract

backgroundSquamous cell carcinoma (SCC) of unknown primary (SCCUP) refers to any SCC for which the primary tumor origin cannot be identified despite guideline-directed evaluation. Although strategies employing comprehensive genomic profiling (CGP) to identify targets for non-SCC carcinomas of unknown primary (CUPs) have shown benefit, the genomic landscape in SCCUP remains poorly defined. Here we describe results of CGP in patients with SCCUP to identify potential therapy targets and characteristic biomarkers. PATIENTS AND

methodsCases of advanced SCCUP were identified in the FoundationCORE® database by review of clinical history and pathology records. Samples underwent DNA extraction and sequencing to identify genomic alterations (GAs), microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic mutational signatures, and viral reads. Programmed death-ligand 1 (PD-L1) expression was determined by immunohistochemistry.

results443 SCCUP cases were identified. Common presentation sites included lymph nodes (41.1%), liver (15.6%), and soft tissue (15.1%). A mean of 6.5 GAs were observed per case. The most frequent non-targetable GAs involved TP53 (62.5%), CDKN2A (37.0%), CDKN2B (19.6%), KMT2D (18.3%), and TERT (16.0%); the most frequent GAs potentially targetable in biomarker-driven trials included PIK3CA (27.3%), PTEN (15.1%), MTAP (13.1%), KRAS (10.4%), and NOTCH1 (8.4%). Among all SCCUP cases, 2.0% had MSI-high (MSI-H) status and 33.9% had TMB ≥10 mutations/megabase. Among 204 cases with available PD-L1 testing, 39.2% were low-positive [tumor proportion score (TPS) 1%-49%] and 29.9% were high-positive (TPS ≥50%). SCCUP cases presenting with liver involvement had fewer GAs per tumor and lower TMB compared with other SCCUP cases. In contrast, cases presenting with inguinal, pelvic, or retroperitoneal involvement were more likely to demonstrate evidence of human papilloma virus (HPV) infection and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) genomic signatures.

conclusionsCGP of this SCCUP cohort identified GAs that may guide consideration of molecularly targeted therapy via tumor-agnostic indications and/or treatment in biomarker-driven trials. SCCUPs frequently exhibit biomarkers associated with response to immune checkpoint inhibitors.

Indexed as

Carcinoma, Squamous CellNeoplasms, Unknown PrimaryAdultAgedAged, 80 and overB7-H1 AntigenBiomarkers, TumorFemaleGenomicsHumansMaleMicrosatellite InstabilityMiddle AgedMutationB7-H1 AntigenBiomarkers, Tumorbiomarkercarcinoma of unknown primary (CUP)comprehensive genomic profiling (CGP)molecularly targeted therapysquamous cell carcinoma of unknown primary (SCCUP)squamous cell carcinoma (SCC)

Identifiers

PMID40499462
PMCPMC12182777

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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 OpenQuestion graph.