Early-Onset Oral Squamous Cell Carcinoma: Emerging Biological Insights, Risk Factors and Clinical Implications

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine Pub Date : 2026-07-05 Epub Date: 2026-03-15 DOI:10.1111/jop.70130

Gennaro Musella, Cristina D'Antonio, Federica Canfora, Michele D. Mignogna, Valentino Vellone, Vito Carlo Alberto Caponio, Amerigo Giudice, Alessandro Villa, Daniela Adamo

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引用次数: 0

Abstract

Background

Early-onset oral squamous cell carcinoma (EO-OSCC), commonly defined as occurring in individuals under 50 years of age, is increasingly recognized as a potentially distinct clinical subset with differences in exposure patterns and tumor biology compared with conventional oral squamous cell carcinoma (OSCC). Unlike typical OSCC, which is strongly associated with tobacco and alcohol, EO-OSCC more frequently affects never-smokers/never-drinkers, posing challenges for early recognition, risk stratification, and management.

Objective

This review integrates evidence mapping with narrative synthesis to summarize current knowledge on EO-OSCC, focusing on epidemiology, emerging risk factors, molecular alterations, tumor microenvironment characteristics, and clinical implications.

Methods

Literature was searched across PubMed, Scopus, Embase, Web of Science, and the Cochrane Library up to August 2025, complemented by global cancer databases (GLOBOCAN/Cancer Tomorrow) and international trial registries.

Results

Available data suggest distinct biological features, including relatively low tumor mutational burden, recurrent alterations in CDKN2A, TP53, NOTCH1, and EGFR, epigenetic dysregulation, and a checkpoint-dominant immunosuppressive tumor microenvironment. Alongside traditional carcinogens, modifiable determinants such as sugar-sweetened beverages, electronic cigarette use, and oral microbial dysbiosis have emerged as plausible contributors, although evidence remains heterogeneous. Despite frequently aggressive histopathologic features, younger patients may tolerate intensive multimodal therapies better and achieve favorable outcomes.

Conclusion

These findings highlight the urgent need for age-specific prognostic tools, biomarker-guided therapies, and early detection protocols. International collaboration will be key to improving survival and long-term quality of life in this growing patient population.

Abstract Image

查看原文本刊更多论文

早发性口腔鳞状细胞癌：新出现的生物学见解、危险因素和临床意义。

背景：早发性口腔鳞状细胞癌（EO-OSCC）通常定义为发生在50岁以下的个体，与传统口腔鳞状细胞癌（OSCC）相比，它越来越被认为是一个潜在的独特临床亚群，在暴露模式和肿瘤生物学上存在差异。与典型的OSCC（与烟草和酒精密切相关）不同，EO-OSCC更常影响不吸烟/不饮酒的人，这给早期识别、风险分层和管理带来了挑战。目的：本综述结合证据图谱和叙事综合来总结目前关于EO-OSCC的知识，重点是流行病学、新出现的危险因素、分子改变、肿瘤微环境特征和临床意义。方法：在PubMed、Scopus、Embase、Web of Science和Cochrane Library检索截至2025年8月的文献，并辅以全球癌症数据库（GLOBOCAN/ cancer Tomorrow）和国际试验注册。结果：现有数据显示了不同的生物学特征，包括相对较低的肿瘤突变负担，CDKN2A、TP53、NOTCH1和EGFR的复发性改变，表观遗传失调，以及检查点优势的免疫抑制肿瘤微环境。除了传统的致癌物外，可改变的决定因素，如含糖饮料、电子烟使用和口腔微生物生态失调，已成为可能的致病因素，尽管证据仍不一致。尽管经常具有侵袭性的组织病理学特征，年轻患者可能更好地耐受强化多模式治疗并获得良好的结果。结论：这些发现强调了对年龄特异性预后工具、生物标志物引导疗法和早期检测方案的迫切需求。国际合作将是提高这一不断增长的患者群体的生存率和长期生活质量的关键。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Oral Pathology & Medicine 医学-病理学

CiteScore

5.90

自引率

6.10%

发文量

121

审稿时长

4-8 weeks

期刊介绍： The aim of the Journal of Oral Pathology & Medicine is to publish manuscripts of high scientific quality representing original clinical, diagnostic or experimental work in oral pathology and oral medicine. Papers advancing the science or practice of these disciplines will be welcomed, especially those which bring new knowledge and observations from the application of techniques within the spheres of light and electron microscopy, tissue and organ culture, immunology, histochemistry and immunocytochemistry, microbiology, genetics and biochemistry.