Prognostic role of histological depth of invasion in T1-2 oropharyngeal squamous cell carcinoma 

Linda Nissi et al.

Am J Otolaryngol. 2026 Jun 10;47(4):104869. doi: 10.1016/j.amjoto.2026.104869. Online ahead of print.

Published on June 12, 2026

 

ABSTRACT

BACKGROUND: Depth of invasion (DOI) is a well-established prognostic factor in oral cavity squamous cell carcinoma (OSCC). Incorporating DOI into the OSCC staging system has substantially refined T-classification and now informs key management decisions in patients with early-stage (T1-T2) disease. In contrast, the prognostic significance of DOI in oropharyngeal squamous cell carcinoma (OPSCC) remains relatively unclear. The aim of this study was to evaluate the prognostic value of DOI in T1-2 OPSCC.

MATERIALS AND METHODS: A population-based cohort representative of 1033 head and neck squamous cell carcinoma patients was used to identify T1-2 OPSCC patients treated with a curative intent and a tumor sample available for DOI measurement.

RESULTS: In this retrospective cohort study of 74 patients, of whom 63.8% (n = 44) were p16-positive, 71.6% (n = 53) had a DOI ≥ 5 mm. While high DOI correlated with heavy alcohol consumption, it did not predict survival outcomes (5-year disease-specific survival HR 1.06; 95% CI 0.94-1.20; p = 0.315) or locoregional metastasis (HR 1.54; 95% CI 0.51-4.63; p = 0.444) in T1-2 tumors of the oropharynx. Instead, within the p16-negative cohort, increased DOI (≥ 5 mm) was associated with an observable tendency toward poorer survival.

CONCLUSION: DOI was not a prognostic factor in p16-positive T1-2 OPSCC. Nevertheless, DOI may hold prognostic relevance for p16-negative disease. The patterns of local invasion and locoregional spread in OPSCC may reflect distinct biological mechanisms compared to those in other head and neck subsites.

PMID:42285029 | DOI:10.1016/j.amjoto.2026.104869

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