With the growing interest in treatment de-intensification trials for human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPC), accurate patient stratification has become essential for patient selection. The aim of this study was to validate the prognostic ability of the AJCC/UICC TNM 8th edition (8th Ed) for HPV+ OPC.
Patients with HPV+ OPC treated with curative (chemo)radiotherapy ((C)RT) between 2004 and 2017 were classified according to the TNM 7th edition (7th Ed) and the new clinical TNM 8th Ed. HPV status was determined by p16 immunohistochemistry staining. The 5-year overall survival (5YOS) was estimated using the Kaplan-Meier method and groups were compared using the log-rank test. Harrell’s C-index was used as measure of model performance.
A total of 333 OPC were identified of whom 100 were HPV+. The median follow-up was 63.7 months (IQR 30.0;99.9). The 5Y-OS with the 7th Ed were stage I/II 88.9% (CI95% 43.3;98.4), stage III 70.0% (CI95% 22.5;91.8), stage IVa 71.4% (CI95% 57.3;81.6) and stage IVb 29.8% (1.4;71.1) (p = 0.38). With the TNM 8th Ed, the 5Y-OS of stage I, II and III were 91.6% (CI95% 76.1;97.2), 55.2% (CI95% 29.2;75.1) and 38.0% (CI95% 8.7;68.2) (p = 0.006). On Cox regression analysis, when compared to stage I, OS was significantly lower for stage II (p = 0.018, Hazard ratio (HR)= 4.24 (CI95% 1.27;14.13)) and for stage III (p = 0.004, HR = 5.40 (CI95% 1.69;17.26)). Nevertheless, there was no significant difference between stage II and III (p = 0.60, HR = 1.27 (CI95% 0.51;3.17)). The Harrell’s C-index for TNM 8th Ed stage was 0.67.
Although the TNM 8th Ed provides better OS stratification than the 7th Ed for HPV+ OPC following (C)RT, better prognostic models are needed due to the lack of differentiation between stage II and stage III. This study emphasizes the importance of further research in patient selection and personalized treatment for HPV+ OPC.
Clinical trial identification
Legal entity responsible for the study
The ethics committee of the University Hospitals of Leuven.
Grant from Stand up to Cancer (Kom op tegen kanker), the Flemish cancer society.
S. Deschuymer: Grant: Stand up to Cancer (Kom op tegen kanker), the Flemish cancer society. All other authors have declared no conflicts of interest.