title: The association between human papillomavirus and oropharyngeal squamous cell Carcinoma: Reviewed according to the Bradford Hill criteria for causality.
abstract: There is emerging evidence of the association between human papillomavirus and a subset of head and neck cancers. However, the role of human papillomavirus as a causal factor is still debated. This review addresses the association between human papillomavirus and oropharyngeal squamous cell carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils. The association is geographically consistent throughout the economically developed world. The presence and integration of high-risk human papillomavirus genome in tonsillar tumours, and expression of viral oncogenes, are specific and plausible. Analogous to human papillomavirus in cervical cancer, the rising incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Electronic address: lena@walvik.no.
authors.forename: Lena
authors.initials: L
authors.lastname: Walvik
authors.affiliation: Emergency Department, Ystad Hospital, Kristianstadsvaegen 3, 271 33 Ystad, Sweden. Electronic address: amanda.bjork.svensson@gmail.com.
authors.forename: Amanda Björk
authors.initials: AB
authors.lastname: Svensson
authors.affiliation: Department of Oncology, Section 5073, Finsencentret Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Electronic address: jeppe.friborg@regionh.dk.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Friborg
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Electronic address: Christel.Lajer@regionh.dk.
authors.forename: Christel Bræmer
authors.initials: CB
authors.lastname: Lajer
mesh_terms: D052685:Alphapapillomavirus / Q000254:growth & development / Q000472:pathogenicity*; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D006801:Humans; D009959:Oropharyngeal Neoplasms / Q000821:virology*
chemical_list: D004279:DNA, Viral
keywords: Bradford Hill criteria; Causality; Human papillomavirus; Oropharyngeal squamous cell carcinoma; Tonsillar neoplasms