Evidence map›Paper›PMID 42125931›Full record

SynthesisJournal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology2026

The Prognostic Significance of Tertiary Lymphoid Structures in Head and Neck Cancers: A Systematic Review and Meta-Analysis.

Everton Freitas de Morais, Bruno Cesar da Costa, Antti Mäkitie, Ricardo D Coletta, Alhadi Almangush

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

5 authors.

Everton Freitas de MoraisDepartment of Oral Diagnosis, and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, São Paulo, Brazil.ORCID https://orcid.org/0000-0002-2173-7672
Bruno Cesar da CostaDepartment of Oral Diagnosis, and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, São Paulo, Brazil.
Antti MäkitieDepartment of Otorhinolaryngology, Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.ORCID https://orcid.org/0000-0002-0451-2404
Ricardo D ColettaDepartment of Oral Diagnosis, and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, São Paulo, Brazil.
Alhadi AlmangushResearch Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico 305781/2024-3Fundação de Amparo à Pesquisa do Estado de São Paulo 2022/00994-5Fundação de Amparo à Pesquisa do Estado de São Paulo 2023/10632-6
6 · The paper itself

Abstract

backgroundHead and neck squamous cell carcinoma (HNSCC), particularly oral squamous cell carcinoma (OSCC), is associated with poor survival despite therapeutic advances. Tertiary lymphoid structures (TLSs) are emerging components of the tumor microenvironment, but their prognostic significance in HNSCC remains unclear.

objectiveTo systematically review and meta-analyze the prognostic impact of TLSs in HNSCC.

methodsPubMed/MEDLINE, Scopus, ScienceDirect, and Embase were searched through August 2025. Eligible studies evaluated TLS presence, density, maturity, or spatial distribution in histologically confirmed HNSCC. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed-effects models. Risk of bias and certainty of evidence were assessed using QUIPS and GRADE, respectively.

resultsSeventeen studies involving more than 2309 patients were included. TLS-positive tumors were significantly associated with improved overall and disease-free survival (DFS) (p < 0.001). Absence of TLSs was associated with worse overall survival (HR: 2.20, 95% CI: 1.74-2.78, I

conclusionTLSs are strong prognostic biomarkers in HNSCC. Their presence, maturity, and spatial context significantly influence survival, supporting their role in prognostic stratification and future therapeutic strategies. TLS maturity emerges as a promising feature for standardized scoring systems and should be further explored in future studies.

Indexed as

Head and Neck NeoplasmsSquamous Cell Carcinoma of Head and NeckTertiary Lymphoid StructuresDisease-Free SurvivalHumansPrognosisTumor Microenvironmenthead and neck squamous cell carcinomaoral squamous cell carcinomaprognostic biomarkerssurvival analysistertiary lymphoid structurestumor microenvironment

Identifiers

PMID42125931
PMCPMC13429375

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

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.