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Peer-reviewedCC BY 4.0Journal of Clinical Medicine

Prognostic Value of Tumor Budding and Worst Pattern of Invasion in Clinically Node-Negative Early-Stage Lip and Oral Cavity Squamous Cell Carcinoma: A Systematic Review

  • Mădălina Anca Moldovan1
  • Laura-Veronica Filip2
  • Cristian Niky Cumpată3
  • Bogdan Andrei Bumbu4
  • Paolo Di Francesco5
  • Călin Rareș Roman1
5 affiliations
  1. 1Department of Oro-Maxillo-Facial Surgery and Implantology, Faculty of Dental Medicine, Iuliu Hațieganu University, 400012 Cluj-Napoca, Romania
  2. 2Private Practice, Filip Laura-Veronica, 400584 Cluj-Napoca, Romania
  3. 3Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Titu Maiorescu University, 031593 Bucharest, Romania
  4. 4Department of Dental Medicine, University of Oradea, 410073 Bihor, Romania
  5. 5Department of Prosthodontics, Faculty of Dental Medicine, Titu Maiorescu University, 031593 Bucharest, Romania
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Abstract

Background: Early-stage squamous cell carcinoma of the lip and oral cavity may behave aggressively despite clinically negative cervical lymph nodes. Tumor budding (TB) and worst pattern of invasion (WPOI) have been proposed as histopathological markers of invasive behavior, but their prognostic value in cT1–2N0M0 disease remains uncertain. Methods: This PRISMA 2020 systematic review included studies published as eligible full-text journal articles up to 25 April 2026 and was informed by REMARK and guidance for systematic reviews of prognostic factor studies. PubMed and Scopus were searched as bibliographic databases, supplemented by ScienceDirect, Semantic Scholar, and backward and forward citation searching. Eligible studies assessed TB and/or WPOI in resection specimens from surgically treated cT1–2N0M0 lip/oral cavity squamous cell carcinoma and reported nodal, recurrence, or eligible survival outcomes. Risk of bias was evaluated using the Quality In Prognosis Studies (QUIPS) tool. Results: Thirty-eight reports met eligibility criteria; linked or partially overlapping cohorts were treated as related evidence to avoid double counting. Higher-risk WPOI and high-grade TB were associated with cervical nodal disease, locoregional recurrence, and adverse survival across multiple reports, although adjusted effects varied. Eligible survival outcomes included disease-free survival, recurrence-free survival, disease-specific/cancer-specific survival, and overall survival; progression-free survival was excluded. Conclusions: TB and WPOI may provide complementary postoperative prognostic information in clinically node-negative early-stage lip and oral cavity squamous cell carcinoma. Heterogeneity in definitions, thresholds, cervical management, endpoints, and statistical adjustment precluded a single pooled estimate and limits immediate clinical implementation. Neither marker should currently be used as an isolated determinant of treatment decisions.

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Cite

BibTeXRIS
BibTeX
@article{moldovan2026prognostic,
  title = {{Prognostic Value of Tumor Budding and Worst Pattern of Invasion in Clinically Node-Negative Early-Stage Lip and Oral Cavity Squamous Cell Carcinoma: A Systematic Review}},
  author = {Mădălina Anca Moldovan and Laura-Veronica Filip and Cristian Niky Cumpată and Bogdan Andrei Bumbu and Paolo Di Francesco and Călin Rareș Roman},
  journal = {Journal of Clinical Medicine},
  year = {2026},
  month = oct,
  doi = {10.3390/jcm15207949},
  url = {https://www.mdpi.com/2077-0383/15/20/7949},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Prognostic Value of Tumor Budding and Worst Pattern of Invasion in Clinically Node-Negative Early-Stage Lip and Oral Cavity Squamous Cell Carcinoma: A Systematic Review
AU  - Mădălina Anca Moldovan
AU  - Laura-Veronica Filip
AU  - Cristian Niky Cumpată
AU  - Bogdan Andrei Bumbu
AU  - Paolo Di Francesco
AU  - Călin Rareș Roman
PY  - 2026
DA  - 2026/10/14
JO  - Journal of Clinical Medicine
DO  - 10.3390/jcm15207949
UR  - https://www.mdpi.com/2077-0383/15/20/7949
AB  - Background: Early-stage squamous cell carcinoma of the lip and oral cavity may behave aggressively despite clinically negative cervical lymph nodes. Tumor budding (TB) and worst pattern of invasion (WPOI) have been proposed as histopathological markers of invasive behavior, but their prognostic value in cT1–2N0M0 disease remains uncertain. Methods: This PRISMA 2020 systematic review included studies published as eligible full-text journal articles up to 25 April 2026 and was informed by REMARK and guidance for systematic reviews of prognostic factor studies. PubMed and Scopus were searched as bibliographic databases, supplemented by ScienceDirect, Semantic Scholar, and backward and forward citation searching. Eligible studies assessed TB and/or WPOI in resection specimens from surgically treated cT1–2N0M0 lip/oral cavity squamous cell carcinoma and reported nodal, recurrence, or eligible survival outcomes. Risk of bias was evaluated using the Quality In Prognosis Studies (QUIPS) tool. Results: Thirty-eight reports met eligibility criteria; linked or partially overlapping cohorts were treated as related evidence to avoid double counting. Higher-risk WPOI and high-grade TB were associated with cervical nodal disease, locoregional recurrence, and adverse survival across multiple reports, although adjusted effects varied. Eligible survival outcomes included disease-free survival, recurrence-free survival, disease-specific/cancer-specific survival, and overall survival; progression-free survival was excluded. Conclusions: TB and WPOI may provide complementary postoperative prognostic information in clinically node-negative early-stage lip and oral cavity squamous cell carcinoma. Heterogeneity in definitions, thresholds, cervical management, endpoints, and statistical adjustment precluded a single pooled estimate and limits immediate clinical implementation. Neither marker should currently be used as an isolated determinant of treatment decisions.
SN  - 2077-0383
ER  -