title: The prognostic role of sex, race, and human papillomavirus in oropharyngeal and nonoropharyngeal head and neck squamous cell cancer.
abstract: 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).
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Head and Neck Surgery, Department of Otolaryngology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Carole
authors.initials: C
authors.lastname: Fakhry
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.affiliation: Head and Neck Surgery, Department of Otolaryngology, University of California San Francisco, San Francisco, California.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, California.
authors.forename: Annemieke
authors.initials: A
authors.lastname: van Zante
authors.affiliation: Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Yuehan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Head and Neck Surgery, Department of Otolaryngology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Eleni
authors.initials: E
authors.lastname: Rettig
authors.affiliation: Head and Neck Surgery, Department of Otolaryngology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Linda X
authors.initials: LX
authors.lastname: Yin
authors.affiliation: Head and Neck Surgery, Department of Otolaryngology, University of California San Francisco, San Francisco, California.
authors.forename: William R
authors.initials: WR
authors.lastname: Ryan
authors.affiliation: Head and Neck Surgery, Department of Otolaryngology, University of California San Francisco, San Francisco, California.
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Ha
authors.affiliation: Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Alicia
authors.initials: A
authors.lastname: Wentz
authors.affiliation: Head and Neck Surgery, Department of Otolaryngology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Wayne
authors.initials: W
authors.lastname: Koch
authors.affiliation: Head and Neck Surgery, Department of Otolaryngology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Richmon
authors.affiliation: Head and Neck Surgery, Department of Otolaryngology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: David W
authors.initials: DW
authors.lastname: Eisele
authors.affiliation: Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
mesh_terms: D001741:Black or African American / Q000706:statistics & numerical data; D001213:Asian / Q000706:statistics & numerical data; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000401:mortality* / Q000473:pathology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004279:DNA, Viral; D005006:Ethnicity / Q000706:statistics & numerical data*; D005260:Female; D006258:Head and Neck Neoplasms / Q000208:ethnology / Q000401:mortality* / Q000473:pathology / Q000821:virology; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007822:Laryngeal Neoplasms / Q000208:ethnology / Q000401:mortality* / Q000473:pathology / Q000821:virology; D008297:Male; D009062:Mouth Neoplasms / Q000208:ethnology / Q000401:mortality* / Q000473:pathology / Q000821:virology; D009303:Nasopharyngeal Neoplasms / Q000208:ethnology / Q000401:mortality* / Q000473:pathology / Q000821:virology; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D009959:Oropharyngeal Neoplasms / Q000208:ethnology / Q000401:mortality* / Q000473:pathology / Q000821:virology; D050725:Papillomavirus E7 Proteins / Q000378:metabolism; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000821:virology; D011379:Prognosis; D016016:Proportional Hazards Models; D012097:Repressor Proteins / Q000378:metabolism; D012189:Retrospective Studies; D012737:Sex Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D044465:White People / Q000706:statistics & numerical data
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: head and neck squamous cell cancer (HNSCC); human papillomavirus (HPV); oropharyngeal squamous cell cancer (OPSCC); p16; prognosis; race; sex