title: Continuing rise in oropharyngeal cancer in a high HPV prevalence area: A Danish population-based study from 2011 to 2014.
abstract: Human papillomavirus (HPV) is a critical element in the rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), although whether this trend will continue, and the types of HPV responsible, are currently unknown. We previously demonstrated an increased incidence of HPV-related OPSCC in the high HPV prevalence area of Eastern Denmark from 2000 to 2010. Therefore, we investigated if the incidence for OPSCC continued to rise, the association to HPV and putative HPV-types in Eastern Denmark from 2011 to 14. We then projected the expected incidence of OPSCC versus cervical cancer through to 2020.
  
  
  
  Patients with OPSCC (tonsillar squamous cell carcinoma [TSCC] and base of tongue squamous cell carcinoma [BSCC]) were identified via the Danish Head and Neck Cancer Group and the Danish Pathology Databank (n = 700). Tumours were re-reviewed and assessed using p16 immunohistochemistry, HPV DNA polymerase chain reaction (PCR), with genotyping by next generation sequencing.
  
  
  
  Sixty-two percent (432/700) of tumours were HPV-positive (HPV+). The total incidence rate (per 100.000) for OPSCC increased from 4.0 in 2011 to 4.5 in 2014, primarily due to a rise in HPV+ TSCCs and HPV+ BSCCs, although numbers of HPV-negative (HPV-) OPSCC also increased during the study period. The majority of HPV+ tumours were HPV16 DNA positive (86%), but we also identified HPV33 DNA (6%), HPV35 DNA (4%) and others (3%), including HPV18, 26, 31, 45, 56, 58, 59 and HPV67.
  
  
  
  An increasing incidence of OPSCC is driven primarily by HPV+ OPSCC. Sixty-two percent of tumours were HPV+, which is a high-prevalence, although the lower number of HPV- cases has yet to stabilise. HPV16 was the predominant genotype, although a significant proportion (14%) was of another genotype. Our projections suggest that the number of HPV+ OPSCC will exceed that of cervical cancer in 2016 in Eastern Denmark.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark.
authors.forename: Amanda-Louise Fenger
authors.initials: AF
authors.lastname: Carlander
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Grønhøj Larsen
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark.
authors.forename: David Hebbelstrup
authors.initials: DH
authors.lastname: Jensen
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark.
authors.forename: Emilie
authors.initials: E
authors.lastname: Garnæs
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark.
authors.forename: Katalin
authors.initials: K
authors.lastname: Kiss
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark.
authors.forename: Luise
authors.initials: L
authors.lastname: Andersen
authors.affiliation: Department of Pathology, Roskilde Sygehus, Sygehusvej 9, 4000 Roskilde, Denmark.
authors.forename: Caroline Holkmann
authors.initials: CH
authors.lastname: Olsen
authors.affiliation: Department of Pathology, Hvidovre Hospital, Kettegaard Alle 30, 2650 Hvidovre, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Franzmann
authors.affiliation: Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev Ringvej 75, 2730 Herlev, Denmark.
authors.forename: Estrid
authors.initials: E
authors.lastname: Høgdall
authors.affiliation: Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen Oe, Denmark; Department of Gynaecology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark.
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjær
authors.affiliation: Institute of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
authors.forename: Bodil
authors.initials: B
authors.lastname: Norrild
authors.affiliation: Department of Oncology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: Specht
authors.affiliation: Department of Oncology, Herlev Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark.
authors.forename: Elo
authors.initials: E
authors.lastname: Andersen
authors.affiliation: Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: van Overeem Hansen
authors.affiliation: Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark.
authors.forename: Finn Cilius
authors.initials: FC
authors.lastname: Nielsen
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark. Electronic address: Christian.von.buchwald@regionh.dk.
authors.forename: Christian
authors.initials: C
authors.lastname: von Buchwald
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000821:virology; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000453:epidemiology* / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology; D015995:Prevalence
keywords: Base of tongue; Genotype; HPV; HPV16; Incidence; Oropharynx; Tonsillar; p16