title: A high and increasing HPV prevalence in tonsillar cancers in Eastern Denmark, 2000-2010: the largest registry-based study to date.
abstract: The aim was to explore whether the incidence of tonsillar squamous cell carcinomas (TSCCs) increased in Eastern Denmark, 2000-2010, and whether human papillomavirus (HPV) could explain the increase, and to assess the association of HPV prevalence with gender, age, and origin (i.e., the certainty of tonsillar tumor origin). We applied HPV DNA PCR and p16 immunohistochemistry to all TSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and in the Danish Pathology Data Bank (n = 632). Pathologists reviewed and subdivided the tumors into two groups: specified and nonspecified TSCCs. Approximately 10% of HPV-positive tumors was genotyped by amplicon next-generation sequencing. The overall crude incidence of TSCCs increased significantly (2.7% per year) and was explained by an increasing incidence of HPV-positive TSCCs (4.9% per year). The overall HPV prevalence was 58%, with HPV16 being the predominant HPV type. In multivariate analysis, the HPV prevalence was associated with age (<55 vs. >60 years) (OR, 1.72; 95% CI 1.13-2.63) and origin (nonspecified vs. specified TSCCs) (OR, 0.15; 95% CI 0.11-0.22). The association of HPV prevalence with origin increased over time in specified TSCCs (OR per year, 1.10; 95% CI 1.01-1.19), whereas no change over time was observed among nonspecified TSCCs (OR per year, 0.99; 95% CI 0.90-1.08). In conclusion, the observed increase in the number of HPV-positive TSCCs can explain the increasing number of TSCCs in Eastern Denmark, 2000-2010. HPV prevalence was associated with younger age (<55 years) and a high certainty of tonsillar tumor origin.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Emilie
authors.initials: E
authors.lastname: Garnaes
authors.forename: Katalin
authors.initials: K
authors.lastname: Kiss
authors.forename: Luise
authors.initials: L
authors.lastname: Andersen
authors.forename: Marianne H
authors.initials: MH
authors.lastname: Therkildsen
authors.forename: Maria B
authors.initials: MB
authors.lastname: Franzmann
authors.forename: Bettina
authors.initials: B
authors.lastname: Filtenborg-Barnkob
authors.forename: Estrid
authors.initials: E
authors.lastname: Hoegdall
authors.forename: Lene
authors.initials: L
authors.lastname: Krenk
authors.forename: Michael
authors.initials: M
authors.lastname: Josiassen
authors.forename: Christel B
authors.initials: CB
authors.lastname: Lajer
authors.forename: Lena
authors.initials: L
authors.lastname: Specht
authors.forename: Kirsten
authors.initials: K
authors.lastname: Frederiksen
authors.forename: Lennart
authors.initials: L
authors.lastname: Friis-Hansen
authors.forename: Finn C
authors.initials: FC
authors.lastname: Nielsen
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjaer
authors.forename: Bodil
authors.initials: B
authors.lastname: Norrild
authors.forename: Christian
authors.initials: C
authors.lastname: von Buchwald
mesh_terms: D003718:Denmark / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000821:virology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000453:epidemiology*; D015995:Prevalence; D012042:Registries; D014067:Tonsillar Neoplasms / Q000821:virology*
keywords: HPV; oropharyngeal cancer; p16; tonsillar cancer