title: Human papillomavirus and rising oropharyngeal cancer incidence in the United States.
abstract: OBJECTIVE
  Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking.
  
  
  METHODS
  HPV status was determined for all 271 oropharyngeal cancers (1984-2004) collected by the three population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping (Inno-LiPA), HPV16 viral load, and HPV16 mRNA expression. Trends in HPV prevalence across four calendar periods were estimated by using logistic regression. Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonrandom selection and to calculate incidence trends. Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses.
  
  
  RESULTS
  HPV prevalence in oropharyngeal cancers significantly increased over calendar time regardless of HPV detection assay (P trend < .05). For example, HPV prevalence by Inno-LiPA increased from 16.3% during 1984 to 1989 to 71.7% during 2000 to 2004. Median survival was significantly longer for HPV-positive than for HPV-negative patients (131 v 20 months; log-rank P < .001; adjusted hazard ratio, 0.31; 95% CI, 0.21 to 0.46). Survival significantly increased across calendar periods for HPV-positive (P = .003) but not for HPV-negative patients (P = .18). Population-level incidence of HPV-positive oropharyngeal cancers increased by 225% (95% CI, 208% to 242%) from 1988 to 2004 (from 0.8 per 100,000 to 2.6 per 100,000), and incidence for HPV-negative cancers declined by 50% (95% CI, 47% to 53%; from 2.0 per 100,000 to 1.0 per 100,000). If recent incidence trends continue, the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020.
  
  
  CONCLUSIONS
  Increases in the population-level incidence and survival of oropharyngeal cancers in the United States since 1984 are caused by HPV infection.
authors.affiliation: National Cancer Institute, National Institutes of Health, 6120 Executive Blvd, EPS 7072, Rockville, MD 20852, USA. chaturva@mail.nih.gov
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chaturvedi
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Brenda Y
authors.initials: BY
authors.lastname: Hernandez
authors.forename: Weihong
authors.initials: W
authors.lastname: Xiao
authors.forename: Esther
authors.initials: E
authors.lastname: Kim
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.forename: Marc T
authors.initials: MT
authors.lastname: Goodman
authors.forename: Maria
authors.initials: M
authors.lastname: Sibug-Saber
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Lihua
authors.initials: L
authors.lastname: Liu
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: Richard C
authors.initials: RC
authors.lastname: Jordan
authors.forename: Sean
authors.initials: S
authors.lastname: Altekruse
authors.forename: William F
authors.initials: WF
authors.lastname: Anderson
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.forename: Maura L
authors.initials: ML
authors.lastname: Gillison
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000401:mortality / Q000821:virology; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000453:epidemiology* / Q000401:mortality / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification*; D018426:SEER Program; D014481:United States / Q000453:epidemiology