Multicenter study of the association between betapapillomavirus infection and cutaneous squamous cell carcinoma

Cancer Res. 2010 Dec 1;70(23):9777-86. doi: 10.1158/0008-5472.CAN-10-0352. Epub 2010 Nov 23.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Australia / epidemiology
  • Betapapillomavirus / genetics
  • Betapapillomavirus / immunology
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / etiology*
  • Case-Control Studies
  • DNA, Viral / genetics
  • Female
  • Genotype
  • Humans
  • Italy / epidemiology
  • Logistic Models
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / virology
  • Prevalence
  • Risk Factors
  • Skin / pathology
  • Skin / radiation effects
  • Skin / virology
  • Skin Neoplasms / epidemiology
  • Skin Neoplasms / etiology*
  • Time Factors
  • Ultraviolet Rays / adverse effects*

Substances

  • Antibodies, Viral
  • DNA, Viral