Journal 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
By Mădălina Anca Moldovan, Laura-Veronica Filip, Cristian Niky Cumpătă and 3 others.
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.