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.

The Rise of HPV-Positive Oropharyngeal Cancers in the United States

“…Zandberg and colleagues present a survival analysis that was stratified by race and HPV tumor status. Consistent with previous reports (23,24), HPV-positive patients had improved survival as compared with HPV-negative patients after stratifying by race. However, when HPV-negative patients were stratified by race, there was a significant difference in overall survival.…”

Competing causes of death in patients with oropharyngeal cancer treated with radiotherapy

“…The 5-year overall survival among patients of African descent was only 24%. Consistent with previously published work, efforts to improve outcome in African-American patients by earlier diagnosis and improved treatment for HPV-negative disease are urgently required (20).…”

“…The improved prognosis associated with oropharyngeal cancers in recent years may be related to increased utilization of concurrent chemoradiation, technological advances in radiation delivery and the increasing prevalence of HPV-related tumors (5,9,12). Caucasian ethnicity and high grade tumors have both been associated with HPV-related tumors and likely account for some of the improved prognosis observed in those subgroups (13,20). The 5-year overall survival among patients of African descent was only 24%.…”

Preventing Cancer with Vaccines: Progress in the Global Control of Cancer

“…Virtually all HPV-related cancer in the head and neck occurs in the oropharynx (tonsils and base of tongue), and at least 25% of all head and neck cancers are believed to be HPV-related oropharyngeal cancer; this proportion is increasing to epidemic dimensions in the industrial world, but it is not known whether dramatic increases in this incidence are also occurring in the developing world. In the United States, HPV-related oropharyngeal cancer is primarily a disease of white men, although recent trends indicate that it is increasing in both white and black men (34). Thus, the proportion of head and neck squamous cell cancers (e.g., oral cancer) due to alcohol and tobacco use is declining whereas that due to HPV infection is increasing.…”