Do Beta-Human Papilloma Viruses Cause Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals?

Abstract

studies remain controversial. According to the International Agency for Research of Cancer (IARC) working group, data remains insufficient to establish a causal relationship [3]. The theory of viral oncogenesis first emerged in the 1950s, when Gross et al described a plausible connection. Today, viruses are associated with more than15% of the oncological burden [4][5].Two compelling pieces of evidence in cSCC epidemiology render HPV a thought-provoking virus for causality assessment. First, the increased occurrence of cSCC in organ transplant recipients associated with significantly higher rates of B-HPV which is similar to the human herpes virus-8 (HHV-8) induced Kaposi sarcoma [6][7][8][9]. Second, the proven causality between specific HPV types and the development of cSCC in individuals diagnosed with epidermodysplasia verruciformis [10][11]. This mechanism was established as a rare inherited disorder with mutations in the transmembrane channel genes TMC6 or TMC8 AbstractBackground: Existing epidemiological evidence is controversial regarding the possible association between Beta Human papillomavirus (B-HPV) and cutaneous squamous cell carcinoma (cSCC) in immunocompetent individuals.Objectives: Perform a systematic review of cohort and case-control studies that assessed B-HPV and the risk of cSCC in immunocompetent individuals to assess the current data. Materials and methods:We performed a systematic literature search for studies in humans through March 17, 2014, with no specified start date or language restrictions and employed predefined search criteria. The included studies complied with the predefined inclusion and exclusion criteria and were agreed upon by both authors after review of abstracts and full text. Data extraction included general study information comprising latitude of study location, study design, the number of cases and controls, method of HPV detection and the number of types of HPV detected. Furthermore, study results were designated as the general and/or type specific B-HPV adjusted Odds Ratio or Relative Risk.Results: This is the largest review to be conducted on this topic in healthy individuals. We evaluated 4,056 cSCC cases and 7,067 controls that were collected from 16 casecontrol and 4 cohort studies included in this review. Studies were subdivided into six categories depending on the method of HPV detection used. Among the 20 studies, 18 (90%) showed a significant association between B-HPV and cSCC. More specifically, HPV8 and HPV38 were most commonly reported to have a significant association with cSCC. Conclusion:This systematic review provides further evidence supporting the role of B-HPV in the development of cSCC in healthy individuals and supports a possible type-specific HPV 8, 38 involvements in cSCC. Our findings highlight the need for large multi-center prospective research to validate these associations.