2839 - Reevaluating Hypopharyngeal Cancer Staging: The Role of HPV Status in Prognosis

Purpose/Objective(s): HPV status is a well-established prognostic factor in head and neck cancers, particularly oropharyngeal squamous cell carcinoma (SCC), influencing TNM staging changes between AJCC 7th and 8th editions. Although HPV positivity occurs in up to 24% of hypopharyngeal (HPX) cancers, its prognostic impact remains underexplored. Given potential survival differences, we investigated the association between HPV status and survival outcomes in non-metastatic HPX SCC and its implications for staging and treatment.

Materials/Methods: We conducted a retrospective cohort study using the National Cancer Database (NCDB) to identify non-metastatic HPX SCC cases (2004–2019). Data on demographics, clinical variables (age, gender, race, comorbidities, insurance, TNM staging, HPV status, treatment) were extracted. Exclusion criteria included age <18, metastatic disease, missing HPV status, or incomplete data. Descriptive statistics characterized the cohort, and Cox proportional hazards regression assessed the relationship between HPV status and overall survival (OS).

Results: Among 2,909 patients with known HPV status, 2,323 were HPV-negative and 586 were HPV-positive. Median age was 64 (HPV-negative) vs. 62 years (HPV-positive). On multivariate Cox regression, HPV status (p < 0.001), age, insurance, grade, T stage, and treatment (all p < 0.01) were significant prognostic factors for OS. Median OS was 78 months for HPV-positive (95% CI: 73.77–83.0 months) vs. 54.1 months for HPV-negative (95% CI: 51.03–57.3 months). In subgroup analysis by stage, HPV-positive patients had significantly better OS except for stage II. Among those receiving definitive chemoradiation plus surgery (HPV-positive: n = 251, HPV-negative: n = 833), OS was 89.7 (95% CI: 83.0–96.44 months) for HPV positive vs. 58.2 months (95% CI: 53.1–63.37 months) for HPV negative (p < 0.01). Notably, N stage was not significant (p = 0.238) in HPV-positive patients, with median OS of 81.6 (N1), 82.5 (N2), and 52.1 (N3) months, suggesting current N staging lacks prognostic relevance in this subset.

Conclusion: HPV status is a strong independent prognostic factor in non-metastatic HPX SCC. HPV-positive patients have significantly better OS, and the TNM system may not fully capture this prognostic difference. These findings highlight the need for revised staging incorporating HPV status to guide treatment and improve prognostication. Further research should refine staging criteria and explore underlying biological mechanisms.