Background: High-risk human papilloma virus (HPV) has been established as prognostic and predictive factor in oropharyngeal cancers. However, its prognostic implication in non-oropharyngeal head and neck squamous cell cancers is elusive. We hypothesize that HPV (p16+) status is predictive of treatment effect and has positive prognostic impact in squamous cell carcinoma of hypopharynx (HypSCC).
Purpose: To evaluate prevalence frequency, clinical characteristics, prognostic impact of p16+ status and prognostic stratification ability of current American Joint Committee on Cancer (AJCC) staging in HypSCC.
Methods: We queried the National Cancer Database (data from 1,500 CoC centers, 70% of newly diagnosed cancers nationwide, including VA cancer centers) from 2010-2015 for patients with HypSCC with known HPV status.
Results: Amongst 10,577 hypopharyngeal cancer patients, 3,043 had squamous cell histology with known HPV status and no distant metastasis. Median age was 63.79 years, 2,419 (79%) were males, median follow-up was 25.12 months. p16+ status was prevalent in 614 (20%). Hyp-SCC p16+ were more often whites (87% vs 81%; P = .02), younger (60 years 50% vs 39%, P < .001), higher socioeconomic status P < .05, poorly differentiated (35% vs 31%; P = .02), lower T stage(P < .001) and higher N stage (P = .001). Median OS of p16- vs. p16+ was 30 months vs not reached (P < .001). Multivariate cox-regression revealed p16 status, age, comorbidity index, type of insurance, T stage, N stage and treatment modality as significant prognostic factors. HypSCC p16- subgroup: OS was worse with chemoradiation vs. surgery radiation (34 vs 61 months; P <
.001). HypSCC p16+ subgroup: OS was better with chemoradiation vs surgery radiation (not reached vs .63 months; P < .001). HypSCC p16+ subgroup analysis showed no difference in OS in different AJCC stage groups (P = .182); AJCC T stage stratification significantly differentiated OS
(P < .001); N staging failed to differentiate OS (P = .99). HypSCC p16+ multivariate analysis showed treatment modalities, insurance type and AJCC T stage as significant prognostic factors for OS.
Conclusions/Implications: HPV positive status is a positive prognostic factor for HypSCC and predictive of better outcomes with chemoradiation. HPV status should guide treatment selection for HypSCC patients and future trials should stratify HypSCC patients based on HPV status. Current AJCC stage grouping fails to stratify HypSCC p16+ into optimal prognostic groups; hence, staging needs to be revisited. Health care disparities may affect survival outcomes and should be further investigated to mitigate this difference.