Human papillomavirus (HPV) infections and their associations with squamous cell neoplasia

Current data implicating an etiological role of Human papillomavirus (HPV) infections in precancer lesions (intraepithelial neoplasia) and squamous cell carcinoma of both the genital tract and other sites (oral cavity, larynx, skin, esophagus, nasal cavity, bronchus) can be summarized as follows: a) HPV involvement in benign, precancer, and malignant genital squamous cell lesions has been demonstrated by morphological, immunohistochemical and DNA hybridization techniques; b) HPV infections in the genital tract are sexually transmitted (STD) and associated with the same risk factors as development of cervical carcinoma; c) natural history of cervical HPV lesions is equivalent to that of CIN, i.e. they are potentially progressive to carcinoma in situ; d) latent HPV infections exist in the genital tract of both sexes; e) animal models exist, where papillomaviruses induce malignant transformation; f) HPV 11 induces transformation of human squamous epithelium in vivo (nude mouse renal subcapsule assay); g) malignant transformation of HPV lesions seems to depend on virus type and the physical state of its DNA, i.e. whether or not integrated in the host cell DNA; h) malignant transformation most probably requires synergistic actions between HPV and chemical or physical carcinogens or other infectious agents; i) genetic disposition (at least in animals) significantly contributes to malignant transformation; j) immunological defence mechanisms of the host probably are capable of modifying the course of HPV infection (efficacy in man remains to be elucidated). Many details of the molecular mechanisms still remain to be clarified, however. No applicable model systems exist to elucidate these issues, or the mechanisms leading to the progression 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.