The prognostic role of sex, race, and human papillomavirus in oropharyngeal and nonoropharyngeal head and neck squamous cell cancer

Abstract

Background: Human papillomavirus (HPV) is a well-established prognostic marker for oropharyngeal squamous cell cancer (OPSCC). Because of the limited numbers of women and nonwhites in studies to date, sex and racial/ethnic differences in prognosis have not been well explored. In this study, survival differences were explored by the tumor HPV status among 1) patients with OPSCCs by sex and race and 2) patients with nonoropharyngeal (non-OP) head and neck squamous cell cancers (HNSCCs).

Methods: This retrospective, multi-institution study included OPSCCs and non-OP HNSCCs of the oral cavity, larynx, and nasopharynx diagnosed from 1995 to 2012. Race/ethnicity was categorized as white non-Hispanic, black non-Hispanic, Asian non-Hispanic, and Hispanic of any race. Tumors were centrally tested for p16 overexpression and the presence of HPV by HPV16 DNA and high-risk HPV E6/E7 messenger RNA in situ hybridization. Kaplan-Meier and Cox proportional hazards models were used to evaluate overall survival (OS).

Results: The study population included 239 patients with OPSCC and 621 patients with non-OP HNSCC with a median follow-up time of 3.5 years. After adjustments for the tumor HPV status, age, current tobacco use, and stage, the risk of death was lower for women versus men with OPSCC (adjusted hazard ratio, 0.55; P = .04). The results were similar with p16. In contrast, for non-OP HNSCCs, HPV positivity, p16 positivity, and sex were not associated with OS.

Conclusions: For OPSCC, there are differences in survival by sex, even after the tumor HPV status has been taken into account. For non-OP HNSCC, the HPV status and the p16 status are not of prognostic significance. Cancer 2017;123:1566-1575. © 2017 American Cancer Society.

Keywords: head and neck squamous cell cancer (HNSCC); human papillomavirus (HPV); oropharyngeal squamous cell cancer (OPSCC); p16; prognosis; race; sex.

Figure 1

Overall survival by the tumor HPV status and p16 immunohistochemistry for OPSCC patients (n = 239) and non-OP HNSCC patients (n = 621). (A) Overall survival for HPV-positive patients with OPSCC (n = 134) and HPV-negative patients with OPSCC (n = 105) was 78.6% and 42.0%, respectively, at 5 years and 57.6% and 28.8%, respectively, at 10 years. (B) Overall survival for patients with p16-positive OPSCC (n = 144) and patients with p16-negative OPSCC (n = 95) was 77.5% and 39.9%, respectively, at 5 years and 55.2% and 29.1%, respectively, at 10 years. (C) Overall survival for HPV-positive patients with non-OP HNSCC (n = 30) and HPV-negative patients with non-OP HNSCC (n = 590) was 55.7% and 52.0%, respectively, at 5 years and 41.8% and 36.4%, respectively, at 10 years. (D) Overall survival for patients with p16-positive non-OP HNSCC (n = 62) and patients with p16-negative non-OP HNSCC (n = 559) was 61.4% and 51.0%, respectively, at 5 years and 44.0% and 35.8%, respectively, at 10 years. HNSCC indicates head and neck squamous cell cancer; HPV, human papillomavirus; non-OP, nonoropharyngeal; OPSCC, oropharyngeal squamous cell cancer.

Figure 2

Survival by sex and race/ethnicity among OPSCC and non-OP HNSCC patients. (A) Overall survival for men (n = 160) and women (n = 79) with OPSCC was 58.3% and 73.1%, respectively, at 5 years and 39.6% and 58.1%, respectively, at 10 years. (B) Overall survival for white (n = 103), black (n = 94), Asian (n = 21), and Hispanic patients (n = 21) with OPSCC was 64.7%, 51.3%, 89.4%, and 76.2%, respectively, at 5 years and 56.8%, 30.0%, 65.2%, and 44.4%, respectively, at 10 years. (C) Overall survival for men (n = 389) and women (n = 232) with non-OP HNSCCs was 51.1% and 53.5%, respectively, at 5 years and 33.9% and 40.7%, respectively, at 10 years. (D) Overall survival for white (n = 212), black (n = 182), Asian (n = 149), and Hispanic patients (n = 78) with non-OP HNSCCs was 56.0%, 45.5%, 57.5%, and 45.5%, respectively, at 5 years and 42.2%, 28.6%, 43.3%, and 26.6%, respectively, at 10 years. HNSCC indicates head and neck squamous cell cancer; non-OP, nonoropharyngeal; OPSCC, oropharyngeal squamous cell cancer.