title: Differences in the Prevalence of Human Papillomavirus (HPV) in Head and Neck Squamous Cell Cancers by Sex, Race, Anatomic Tumor Site, and HPV Detection Method.
abstract: OBJECTIVE
  Human papillomavirus (HPV) causes an increasing proportion of oropharyngeal squamous cell carcinomas (OPSCCs), particularly in white men. The prevalence of HPV among other demographic groups and other anatomic sites of HNSCC is unclear.
  
  
  OBJECTIVE
  To explore the role of HPV tumor status among women and nonwhites with OPSCC and patients with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC).
  
  
  METHODS
  Retrospective cohort study at 2 tertiary academic centers including cases diagnosed 1995 through 2012, oversampled for minorities and females. A stratified random sample of 863 patients with newly diagnosed SCC of the oral cavity, oropharynx, larynx, or nasopharynx was used.
  
  
  METHODS
  Outcomes were HPV status as measured by p16 immunohistochemical analysis, HPV16 DNA in situ hybridization (ISH), and high-risk HPV E6/E7 mRNA ISH.
  
  
  RESULTS
  Of 863 patients, 551 (63.9%) were male and median age was 58 years (interquartile range, 51-68 years). Among 240 OPSCCs, 144 (60%) were p16 positive (p16+), 115 (48%) were HPV16 DNA ISH positive (ISH16+), and 134 (56%) were positive for any oncogenic HPV type (ISH+). From 1995 to 2012, the proportion of p16+ OPSCC increased significantly among women (from 29% to 77%; P = .005 for trend) and men (36% to 72%; P < .001 for trend), as well as among whites (39% to 86%; P < .001 for trend) and nonwhites (32% to 62%; P = .02 for trend). Similar results were observed for ISH+ OPSCC (P ≤ .01 for all). Among 623 non-OP HNSCCs, a higher proportion were p16+ compared with ISH positive (62 [10%] vs 30 [5%]; P = .001). A high proportion (26 of 62 [42%]) of these p16+ non-OP HNSCCs were found in sites adjacent to the oropharynx. The proportion of p16+ and ISH+ non-OP HNSCCs were similar by sex. Over time, the proportion of non-OP HNSCCs that were p16+ (or ISH+) increased among whites (P = .04 for trend) but not among nonwhites (each P > .51 for trend). Among OPSCCs, p16 had high sensitivity (100%), specificity (91%), and positive (93%) and negative predictive value (100%) for ISH positivity. In non-OP HNSCCs, p16 had lower sensitivity (83%) and positive predictive value (40%) but high specificity (94%) and negative predictive value (99%) for ISH positivity.
  
  
  CONCLUSIONS
  During 1995 through 2012, the proportion of OPSCCs caused by HPV has increased significantly. This increase was not restricted to white men but was a consistent trend for women and men, as well as for white and nonwhite racial groups. Few non-OP HNSCCs were HPV related. P16 positivity was a good surrogate for ISH+ tumor status among OPSCC, but not a good surrogate for non-OP HNSCC.
authors.affiliation: Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland.
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
authors.affiliation: Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, 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 Medical Center, San Francisco, California.
authors.forename: Annemieke
authors.initials: A
authors.lastname: van Zante
authors.affiliation: Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland.
authors.forename: Alicia
authors.initials: A
authors.lastname: Wentz
authors.affiliation: Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kluz
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Eleni
authors.initials: E
authors.lastname: Rettig
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California-San Francisco, San Francisco, California.
authors.forename: William R
authors.initials: WR
authors.lastname: Ryan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California-San Francisco, San Francisco, California.
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Ha
authors.affiliation: Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Hyunseok
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Pathology, University of California-San Francisco Medical Center, San Francisco, California.
authors.forename: Justin
authors.initials: J
authors.lastname: Bishop
authors.affiliation: Department of Radiation Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Harry
authors.initials: H
authors.lastname: Quon
authors.affiliation: Department of Radiation Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Kiess
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Richmon
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: David W
authors.initials: DW
authors.lastname: Eisele
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Carole
authors.initials: C
authors.lastname: Fakhry