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.