title: Multicenter study of the association between betapapillomavirus infection and cutaneous squamous cell carcinoma.
abstract: Human papillomaviruses (betaPV) from the beta genus cannot be classified according to their oncogenicity due to a paucity of information. This study evaluates the association between betaPV infection and cutaneous squamous cell carcinoma in conjunction with measures of UV exposure and susceptibility. We performed case-control studies in the Netherlands, Italy, and Australia, countries with profoundly different UV exposures. The presence of 25 betaPV types in eyebrow hair follicles was determined using a highly sensitive HPV DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types in a total of 689 squamous cell carcinoma cases and 845 controls were detected using multiplex serology. Multivariate logistic regression models were used for case-control comparisons and interaction analyses. BetaPV DNA was detected in eyebrow hairs of more than 90% of all participants. The presence of betaPV DNA was associated with an increased risk of squamous cell carcinoma in the Netherlands (OR = 2.8; 95% CI 1.3-5.8) and Italy (OR = 1.7; 95% CI 0.79-3.6), but not in Australia (OR = 0.91; 95% CI 0.53-1.6). Seropositivity for betaPV in controls ranged between 52% and 67%. A positive antibody response against 4 or more betaPV types was associated with squamous cell carcinoma in Australia (OR = 2.2; 95% CI 1.4-3.3), the Netherlands (OR = 2.0; 95% CI 1.2-3.4) and fair-skinned Italians (OR = 1.6, 95% CI 0.94- 2.7). The association between UV susceptibility and squamous cell carcinoma was stronger in betaPV-seropositive people. These combined data support the hypothesis that betaPV may play a role in the development of cutaneous squamous cell carcinoma.
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands. J.N.Bouwes_Bavinck@lumc.nl
authors.forename: Jan Nico
authors.initials: JN
authors.lastname: Bouwes Bavinck
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Neale
authors.forename: Damiano
authors.initials: D
authors.lastname: Abeni
authors.forename: Sylvie
authors.initials: S
authors.lastname: Euvrard
authors.forename: Adele C
authors.initials: AC
authors.lastname: Green
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Harwood
authors.forename: Maurits N C
authors.initials: MN
authors.lastname: de Koning
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldi
authors.forename: Ingo
authors.initials: I
authors.lastname: Nindl
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.forename: Herbert
authors.initials: H
authors.lastname: Pfister
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Proby
authors.forename: Wim G V
authors.initials: WG
authors.lastname: Quint
authors.forename: Jan
authors.initials: J
authors.lastname: ter Schegget
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.forename: Sönke
authors.initials: S
authors.lastname: Weissenborn
authors.forename: Mariet C W
authors.initials: MC
authors.lastname: Feltkamp
mesh_terms: D000368:Aged; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001315:Australia / Q000453:epidemiology; D052686:Betapapillomavirus / Q000235:genetics / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000209:etiology*; D016022:Case-Control Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007558:Italy / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D015995:Prevalence; D012307:Risk Factors; D012867:Skin / Q000473:pathology / Q000528:radiation effects / Q000821:virology; D012878:Skin Neoplasms / Q000453:epidemiology / Q000209:etiology*; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral