title: Second primary cancers after an index head and neck cancer: subsite-specific trends in the era of human papillomavirus-associated oropharyngeal cancer.
abstract: OBJECTIVE
  Patients with head and neck squamous cell carcinoma (HNSCC) are at elevated risk of second primary malignancies (SPM), most commonly of the head and neck (HN), lung, and esophagus. Our objectives were to identify HNSCC subsite-specific differences in SPM risk and distribution and to describe trends in risk over 3 decades, before and during the era of human papillomavirus (HPV) -associated oropharyngeal SCC.
  
  
  METHODS
  Population-based cohort study of 75,087 patients with HNSCC in the Surveillance, Epidemiology, and End Results (SEER) program. SPM risk was quantified by using standardized incidence ratios (SIRs), excess absolute risk (EAR) per 10,000 person-years at risk (PYR), and number needed to observe. Trends in SPM risk were analyzed by using joinpoint log-linear regression.
  
  
  RESULTS
  In patients with HNSCC, the SIR of second primary solid tumor was 2.2 (95% CI, 2.1 to 2.2), and the EAR was 167.7 cancers per 10,000 PYR. The risk of SPM was highest for hypopharyngeal SCC (SIR, 3.5; EAR, 307.1 per 10,000 PYR) and lowest for laryngeal SCC (SIR, 1.9; EAR, 147.8 per 10,000 PYR). The most common SPM site for patients with oral cavity and oropharynx SCC was HN; for patients with laryngeal and hypopharyngeal cancer, it was the lung. Since 1991, SPM risk has decreased significantly among patients with oropharyngeal SCC (annual percentage change in EAR, -4.6%; P = .03).
  
  
  CONCLUSIONS
  In patients with HNSCC, the risk and distribution of SPM differ significantly according to subsite of the index cancer. Before the 1990s, hypopharynx and oropharynx cancers carried the highest excess risk of SPM. Since then, during the HPV era, SPM risk associated with oropharyngeal SCC has declined to the lowest risk level of any subsite.
authors.affiliation: Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. morrisl@mskcc.org
authors.forename: Luc G T
authors.initials: LG
authors.lastname: Morris
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Sikora
authors.forename: Snehal G
authors.initials: SG
authors.lastname: Patel
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Ian
authors.initials: I
authors.lastname: Ganly
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D009959:Oropharyngeal Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications*; D018426:SEER Program