Chapter 8: Human papillomavirus and skin cancer.
A high prevalence of human papillomavirus (HPV) DNA, particularly in squamous cell skin carcinoma of immunosuppressed but also of immunocompetent patients, has renewed great interest in a possible etiologic role of HPV in nonmelanoma skin cancer. It is difficult, however, to interpret these findings against a background of low-level infections with multiple HPV types from supergroup B (HPV4-related and epidermodysplasia verruciformis [EV] HPV), probably acquired by everyone early in and throughout life. Thus far, no high-risk HPV types have been identified. Because of the low copy numbers of HPV DNA in skin cancers, probably not every tumor cell contains a viral genome, which is compatible with cutaneous HPV being possibly important for tumor initiation and progression, but not for maintenance of the malignant phenotype. The question with regard to high-risk types should, therefore, be readdressed in case-control studies on the basis of serology, which can reveal viral activities over years. The viruses lingering in all people are apparently activated by sunlight (UV) exposure, by immunosuppression, and by hyperproliferation of the epithelium (psoriasis) and/or in the specific genetic background of the host (EV). It is intriguing that most of these factors are established risk factors in skin carcinogenesis. The weak transforming activity of cutaneous HPV in vitro compared with the transforming activity of genital HPV may explain the need for activators and synergistic factors. The antiapoptotic activities of E6 proteins of cutaneous HPV could be relevant to oncogenesis in the interplay with UV exposure. Prospective studies should determine the kinetics of HPV activation relative to tumor development.
Pfister
Herbert
H
Institute of Virology, University of Cologne, Fürst-Pückler-Strasse 56, 50935 Cologne, Germany. herbert.pfister@medizin.uni-koeln.de
D002294:Carcinoma, Squamous Cell / Q000821:virology; D004279:DNA, Viral / Q000302:isolation & purification; D015340:Epidemiologic Research Design; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications*; D011565:Psoriasis / Q000821:virology; D012878:Skin Neoplasms / Q000821:virology*; D014412:Tumor Virus Infections / Q000150:complications*; D014466:Ultraviolet Rays / Q000009:adverse effects
D004279:DNA, Viral