The importance of HPV testing in oropharyngeal cancer in two US populations

BACKGROUND: HPV-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) patients have improved survival compared to HPV-negative OPSCC (HPV-) patients (5-year survival rates of ∼80% versus ∼40%). The predictive value of p16 immunohistochemistry (IHC) for HPV+ OPSCC, the most widely used clinical test for HPV status, varies by HPV+ OPSCC prevalence in geographically different populations, but variation within a region is not well described. METHODS: We analyzed p16 IHC and survival in two geographically and demographically diverse OPSCC cohorts of African American (AA, n = 177, Louisiana Tumor Registry) and non-Hispanic white (NHW, n = 392, University of Michigan) patients. RESULTS: HPV+ prevalence was 29.3% in AA versus 86.8% in NHW. p16+ OPSCC was associated with significantly better survival in NHW than in AA patients (HR=4.65, 95% CI: 2.88-7.51, Cox p < 0.0001), adjusting for covariates. AA p16- had worse survival than NHW p16- (log-rank p < 0.001). p16 was less predictive of HPV RNA status for AA than NHW patients (positive predictive value = 65.4% vs. 94.9%, p < 0.05). Among HPV RNA+ patients (79 NHW,17 AA), AA had worse survival than NHW (log-rank p < 0.001). CONCLUSIONS: Survival disparities exist after accounting for heterogeneous HPV+ tumor rates. The PPV of p16 for HPV RNA-defined OPSCC is substantially lower in AA vs NHW patients. Guidelines for HPV testing in OPSCC should be attentive to factors beyond geography.