Biology of human papillomavirus (HPV) infections and their role in squamous cell carcinogenesis

Current data implicating the role of human papillomavirus (HPV) infections in squamous cell carcinogenesis may be summarised as follows: animal models have shown that PVs can induce malignant transformation; HPV involvement in both benign and malignant human squamous cell tumours has been demonstrated by morphological, immunohistochemical and DNA hybridisation techniques; HPV infections in the genital tract are venereally transmitted and are associated with the same risk factors as cervical carcinoma; the natural history of cervical HPV lesions is similar to that of CIN, namely, they have the potential to develop into carcinoma in situ; malignant transformation of PV-induced lesions seems to depend on virus type and the physical state of its DNA, e.g., whether or not it is integrated in the host cell DNA; malignant transformation most probably requires synergistic actions between the PVs and chemical or physical carcinogens, or other infectious agents; genetic disposition (at least in animals) significantly contributes to malignant transformation; immunological defence mechanisms of the host are probably capable of modifying the course of PV infections (efficacy in man remains to be elucidated). Many details of the molecular mechanisms, however, still remain to be clarified. Although BPV1 is capable of transforming fibroblasts, the way that papillomaviruses transform epithelial cells is unclear. Which gene is capable of inducing the limited cell proliferation in benign lesions? No model systems exist to provide the answer nor to elucidate the progression to malignant cells and then to invasive cancer. Improved tissue culture systems for in vitro differentiation of keratinocytes should help in elucidating the biology of papillomaviruses and their interaction with cell division and differentiation.