title: Incidence and risk factors of HPV-related and HPV-unrelated Head and Neck Squamous Cell Carcinoma in HIV-infected individuals.
abstract: OBJECTIVE
  To examine the risk and trends of HPV-related and HPV-unrelated Head and Neck Squamous Cell Carcinoma (HNSCC) in HIV-infected individuals and assess whether immunosuppression (measured through CD4 cell count) and other risk factors impact HNSCC risk.
  
  
  METHODS
  Incident HNSCCs at HPV-related and HPV-unrelated anatomic sites were detected in HIV-infected participants from pooled data from 17 prospective studies in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) between 1996 and 2009. HNSCC cases were validated using chart review or cancer registry matching. Risk factors for incident HPV-related and HPV-unrelated HNSCC were explored using mixed effects Poisson regression in a full prospective analysis, and the effect of CD4 prior to cancer diagnosis was examined in a nested case control analysis.
  
  
  RESULTS
  66 HPV-related and 182 HPV-unrelated incident HNSCCs were detected among 82,375 HIV-infected participants. Standardized incidence ratios (SIRs) for both HPV-related (SIR=3.2, 95%CI=2.5-3.4) and HPV-unrelated (SIR=3.0, 95%CI=2.5-4.1) HNSCC were significantly elevated in HIV-infected individuals compared with the US general population. Between 1996 and 2009, the age-standardized HPV-related HNSCC incidence increased non-significantly from 6.8 to 11.4per 100,000 person-years (p-trend=0.31) while the age-standardized incidence of HPV-unrelated HNSCC decreased non-significantly from 41.9 to 29.3 per 100,000 person-years (p-trend=0.16). Lower CD4 cell count prior to cancer diagnosis was significantly associated with increased HPV-related and HPV-unrelated HNSCC risk.
  
  
  CONCLUSIONS
  The standardized incidence of HPV-related and HPV-unrelated HNSCC are both elevated in HIV-infected individuals. Immunosuppression may have a role in the development of both HPV-related and HPV-unrelated HNSCC.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Baltimore, MD, USA. Electronic address: dbeachl1@jhu.edu.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Beachler
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Baltimore, MD, USA. Electronic address: aabraham@jhsph.edu.
authors.forename: Alison G
authors.initials: AG
authors.lastname: Abraham
authors.affiliation: Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA, USA. Electronic address: Michael.j.silverberg@kp.org.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Silverberg
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Baltimore, MD, USA. Electronic address: yjing@jhsph.edu.
authors.forename: Yuezhou
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins Hospital, 601 N. Caroline St., Baltimore, MD, USA. Electronic address: cfakhry@jhmi.edu.
authors.forename: Carole
authors.initials: C
authors.lastname: Fakhry
authors.affiliation: Department of Medicine, University of Calgary, 3330 Hospital Dr. NW., Calgary, Canada. Electronic address: john.gill@albertahealthservices.ca.
authors.forename: M John
authors.initials: MJ
authors.lastname: Gill
authors.affiliation: Cancer Prevention and Control Program, Yale School of Public Health and Yale School of Medicine, P.O. Box 208034, 60 College Street, New Haven, CT, USA. Electronic address: Robert.dubrow@yale.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Dubrow
authors.affiliation: University of Washington, 325 9th Ave, Seattle, WA, USA. Electronic address: kitahata@uw.edu.
authors.forename: Mari M
authors.initials: MM
authors.lastname: Kitahata
authors.affiliation: Division of Medicine, McGill University, 3655 Sir William Osler, Montreal, Quebec, Canada. Electronic address: marina.klein@mcgill.ca.
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
authors.affiliation: Division of Oncology, Ontario HIV Treatment Network, 1300 Yong St. Suite 600, Toronto, Ontario, Canada. Electronic address: ann.burchell@mail.mcgill.ca.
authors.forename: Ann N
authors.initials: AN
authors.lastname: Burchell
authors.affiliation: Department of Public Health/Preventive Medicine, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., Portland, OR, USA. Electronic address: korthuis@ohsu.edu.
authors.forename: P Todd
authors.initials: PT
authors.lastname: Korthuis
authors.affiliation: Department of Medicine, Johns Hopkins University, 1830 E. Monument St., Baltimore, MD, USA. Electronic address: rdmoore@jhmi.edu.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Moore
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Baltimore, MD, USA. Electronic address: gdsouza2@jhu.edu.
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology*; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000453:epidemiology*; D006258:Head and Neck Neoplasms / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D030361:Papillomavirus Infections / Q000453:epidemiology*; D016012:Poisson Distribution; D011446:Prospective Studies; D012307:Risk Factors
keywords: CD4 T cell count; HIV; HPV; Head and Neck Squamous Cell Carcinoma; NA-ACCORD; Oropharyngeal cancer