Abstract
Background/Objective: The incidence of oropharyngeal cancer (OPC) remains significant, with a rising prevalence of HPV-positive (HPV(+)) cases, underscoring the growing importance of appropriate treatment approaches for this condition. While HPV(+) OPC typically exhibits a more favorable prognosis than HPV-negative (HPV(-)) OPC, certain HPV(+) OPC patients still face adverse outcomes. This study aimed to assess the effectiveness of TORS versus traditional surgery in treating OPC patients and investigate the prognostic implications of specific variants in the HPV genome. Methods: The clinical information, including pathological features, treatments, and outcomes (death), of 135 OPC patients treated with traditional surgery from 2008 to 2018 (the non-TORS group) and 130 OPC patients treated with TORS from 2017 to 2021 (the TORS group) were obtained from Sun Yat-sen University Cancer Center (SYSUCC). A comparative analysis of 3-year overall survival (OS) was performed between these two groups. Furthermore, we conducted next-generation sequencing for the HPV16 genome of the 68 HPV(+) OPC cases to characterize single-nucleotide variations (SNVs) in the HPV16 genome and evaluate its association with HPV(+) OPC patient survival. Results: The comparative analysis of 3-year OS between the two groups (TORS vs. non-TORS) revealed a significant prognostic improvement in the TORS group for OPC patients with a T1-T2 classification (89.3% vs. 72.0%; p = 1.1 × 10(-2)), stages I-II (92.1% vs. 82.2%; p = 4.6 × 10(-2)), and stages III-IV (82.8% vs. 62.2%; p = 5.7 × 10(-2)) and for HPV(-) patients (85.5% vs. 33.3%; p < 1.0 × 10(-6)). Furthermore, three SNVs (SNV1339A>G, SNV1950A>C, and SNV4298A>G) in the HPV16 genome were identified as being associated with worse survival. These SNVs could alter protein interactions and weaken the binding affinity for MHC-II, promoting viral amplification and immune evasion. Conclusions: TORS exhibited a superior prognosis to traditional surgery in OPC patients. Additionally, identifying specific SNVs within the HPV16 genome provided potential prognostic markers for HPV(+) OPC. These significant findings hold clinical relevance for treatment decision-making and prognostic assessment in patients with OPC.