Racial survival disparity in head and neck cancer results from low prevalence of human papillomavirus infection in black oropharyngeal cancer patients

Abstract

The burden of squamous cell carcinoma of the head and neck (SCCHN) is greater for blacks than for whites, especially in oropharyngeal cases. We previously showed retrospectively that disease-free survival was significantly greater in white than in black SCCHN patients treated with chemoradiation, the greatest difference occurring in the oropharyngeal subgroup. Oropharyngeal cancer is increasing in incidence and in its association with human papillomavirus (HPV) infection; HPV-positive oropharyngeal cancer patients have significantly better outcomes (versus HPV-negative). These collective data led to the present analyses of overall survival (OS) in our retrospective cohort and of OS and HPV status (tested prospectively in pretreatment biopsy specimens) in the phase 3, multicenter TAX 324 trial of induction chemotherapy followed by concurrent chemoradiation in SCCHN patients. Median OS in the retrospective cohort of 106 white and 95 black SCCHN patients was 52.1 months (white) versus only 23.7 months (black; P = 0.009), due entirely to OS in the subgroup of patients with oropharyngeal cancer--69.4 months (whites) versus 25.2 months (blacks; P = 0.0006); no significant difference by race occurred in survival of non-oropharyngeal SCCHN (P = 0.58). In TAX 324, 196 white patients and 28 black patients could be assessed for HPV status. Median OS was significantly worse for black patients (20.9 months) than for white patients (70.6 months; P = 0.03) and dramatically improved in HPV-positive (not reached) versus HPV-negative (26.6 months, 5.1 hazard ratio) oropharyngeal patients (P < 0.0001), 49% of whom were HPV-16 positive. Overall, HPV positivity was 34% in white versus 4% in black patients (P = 0.0004). Survival was similar for black and white HPV-negative patients (P = 0.56). This is the first prospective assessment of confirmed HPV status in black versus white SCCHN patients. Worse OS for black SCCHN patients was driven by oropharyngeal cancer outcomes, and that for black oropharyngeal cancer patients by a lower prevalence of HPV infection. These findings have important implications for the etiology, prevention, prognosis, and treatment of SCCHN.

Fig. 1

Racial outcome disparity in the University of Maryland retrospective cohort. A, median OS within the entire cohort (stage III and IV SCCHN treated with concomitant chemotherapy and radiation): 52.1 mo (95% CI, 32.9–65.8) for white patients and 23.7 mo (95% CI, 15.9–33.2) for black patients (log-rank test P = 0.009). B, median OS within the oropharyngeal subset: 69.4 mo (95% CI, 52.1–127.3) for white patients and 25.2 mo (95% CI, 18.4–36.0) for black patients (log-rank test P = 0.0006). C, median OS for patients within the non-oropharyngeal subset: 17.1 mo (95% CI, 10.8–37.0) for white patients and 17.5 mo (95% CI, 11.4–39.0) for black patients (log-rank test P = 0.58). The racial outcome disparity in the overall patient group was entirely due to the disparity in oropharyngeal patients; no disparity was seen in other sites.

Fig. 2

HPV-16 status and OS in the TAX 324 trial. A, median OS by HPV status among all patients: 26.6 mo (95% CI, 19.9–39.6) for HPV-negative (HPV−) patients versus not reached for HPV-positive (HPV+) patients (log-rank test P < 0.0001). B, median OS by HPV status among oropharyngeal patients: 19.7 mo (95% CI, 12.6–34.9) for HPV-negative patients versus not reached for HPV-positive patients (log-rank test P < 0.0001). Fifty-nine of 68 patients with HPV-positive tumors had oropharyngeal cancer.

Fig. 3

Overall survival by race and HPV-16 status in the TAX 324 trial. A, median OS by race in all patients: 70.6 mo [95% CI, 40.0-not reached (NR)] for white patients versus 20.9 mo (95% CI, 12.4-NR) for black patients (log-rank test P = 0.03). B, median OS by race and HPV status (log-rank test P < 0.0001): NR for white HPV-positive (HPV+) patients; 30.1 mo (95% CI, 19.7–42.0) for white HPV-negative (HPV−) patients; and 20.9 mo (95% CI, 12.4-NR) for black patients. The difference in survival between all black patients and HPV-negative white patients was not significant (P = 0.78). Of 32 black patients with an available biopsy, only one was HPV positive. The difference in survival between HPV-positive white patients and all other patients was highly significant (P < 0.0001).