Conditional overall survival analysis of HPV-positive oropharyngeal squamous cell carcinoma

Background: The incidence of HPV-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) has risen drastically in recent years. Conditional overall survival (cOS) provides useful prognostic information for patients who have survived a certain time period following initial treatment, and can inform surveillance guidelines for HPV+ OPSCC. However, cOS for HPV+ OPSCC has not been evaluated in recent years. We sought to characterize residual survivorship among patients who remained alive at 1, 2, or 3 years after diagnosis by evaluating cOS, stratified by tumor staging and associated risk factors, in HPV+ OPSCC based on a large national cancer database. Methods: We identified patients diagnosed with HPV+ OPSCC confirmed by p16 immunohistochemistry from 2018 to 2022 using the Surveillance, Epidemiology, and End Results (SEER) database. Demographics (race, gender, age), treatment modality (radiation, chemotherapy, surgery), and clinicopathological variables (overall staging, tumor size, number of positive regional nodes) were collected. Conditional Kaplan-Meier curves were used to summarize cOS stratified by overall stage and Cox regression models were generated to evaluate if tumor size, age, and performed surgery are associated with cOS. Results: Of the 5298 patients included in the study cohort, 86% were male, 91% were white, 44% had undergone surgery, 84% received radiotherapy, and 64% received chemotherapy. The median age at diagnosis was 61 years old. Increased age (per-year hazard ratio, HR=1.052, 95% CI: 1.042-1.061, p<0.0001) and increased tumor size (for every 10mm increase, HR=1.053, 95% CI: 1.045-1.061, p<0.0001) were associated with increased mortality. Surgery was associated with lower mortality (HR=0.3023, 95% CI: 0.2478-0.3688, p<0.0001). The 4-year overall survival at diagnosis for the study cohort was 83.6% but the cOS increased to 93.5% among patients who had already survived the first two years. Higher disease stage was associated with larger gains in conditional survival. For Stage I patients, 4-year overall survival increased from 90.9% at diagnosis to a cOS of 98.2% among survivors at three years post-diagnosis. Similarly, these increases were from 77.9% to 95.7% for Stage II, 62.7% to 95.2% for Stage III, and 31.7% to 90% for Stage IV patients. Following three years of survival, conditional survival estimates across all stages converged to a high range of 90%-98.2%. Conclusions: For each tumor stage, survival beyond each subsequent year is associated with a higher survival probability to Year 4. Patients with more advanced stage disease saw the largest gains in conditional survival probability over time. These results suggest that the clinical stage of HPV+ OPSCC may have less impact on continued survival after 3 years, which may have implications for prognostication and long-term surveillance. Further work is needed to evaluate these trends over a longer period of time.