title: The changing incidence of human papillomavirus-associated oropharyngeal cancer using multiple imputation from 2000 to 2010 at a Comprehensive Cancer Centre.
abstract: BACKGROUND
  Human papillomavirus (HPV) is a risk and prognostic factor for oropharyngeal cancer (OPC). Determining whether the incidence of HPV-associated OPC is rising informs health policy.
  
  
  METHODS
  HPV status was ascribed using p16 immunohistochemistry in 683/1474 OPC patients identified from the Princess Margaret Hospital's Cancer Registry (from 2000 to 2010). Missing p16 data was estimated using multiple (n=100) imputation (MI) and validated using an independent OPC cohort (n=214). Non-OPC head and neck squamous cell carcinoma (HNSCC) (n=3262) were also used for time-trend comparison. Regression was used to compare HNSCC subsets and time-trends. The c-index was used to measure the predictive ability of MI.
  
  
  RESULTS
  The incidence of OPC rose from 23.3% of all HNSCC in 2000 to 31.2% in 2010 (p=0.002). In the subset of OPC tested for p16, there was no change in p16 positivity over time (p=0.9). However, p16 testing became more frequent over time (p<0.0001), but was nonetheless biased, favouring never-smokers [OR 1.87 (95% CI 1.29-2.70)] and tumors of the tonsil [OR 2.30 (1.52-3.47)] or base-of-tongue [OR 1.72 (1.10-2.70)]. These same factors were also associated with p16-positivity [ORs 3.22 (1.27-8.16), 7.26 (3.50-15.1), 5.83 (2.70-12.7), respectively]. Following MI and normalization, the proportion of OPC that was p16-associated rose from 39.8% in 2000 to 65.0% in 2010, p=0.002, fully explaining the rise in OPC in our patient population.
  
  
  CONCLUSIONS
  The rise in HNSCC referrals seen from 2000 to 2010 at our institution was driven primarily by p16-associated OPC. MI was necessary to derive reliable conclusions when cases with missing data are considerable.
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada M5G2M9.
authors.forename: Steven
authors.initials: S
authors.lastname: Habbous
authors.forename: Karen P
authors.initials: KP
authors.lastname: Chu
authors.forename: Xin
authors.initials: X
authors.lastname: Qiu
authors.forename: Anthony
authors.initials: A
authors.lastname: La Delfa
authors.forename: Luke T G
authors.initials: LT
authors.lastname: Harland
authors.forename: Ehab
authors.initials: E
authors.lastname: Fadhel
authors.forename: Angela
authors.initials: A
authors.lastname: Hui
authors.forename: Bayardo
authors.initials: B
authors.lastname: Perez-Ordonez
authors.forename: Ilan
authors.initials: I
authors.lastname: Weinreb
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
authors.forename: John
authors.initials: J
authors.lastname: Waldron
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Shao Hui
authors.initials: SH
authors.lastname: Huang
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002170:Canada / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D006801:Humans; D007124:Immunoenzyme Techniques; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D027383:Papillomaviridae / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000821:virology; D011379:Prognosis; D013997:Time Factors; D055815:Young Adult
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: Alcohol; Epidemiology; Head and neck cancer; Human papillomavirus; Multiple imputation; P16; Smoking; Squamous cell carcinoma; Trends