Why Do Human Papillomavirus Infections Induce Sharply Demarcated Lesions of the Cervix?

Chronic infections with high-risk human papilloma virus (HPV) have been established to cause cervical cancer. The causal pathogenesis of cervical carcinoma is believed to be the result of the proliferation of one or, at most, a few HPV-transformed cells. So far, it has not been possible to identify and analyze these early initial lesions or cell clusters. Invasive cervical cancer arises in cervical intraepithelial neoplasia, which in turn develops preferentially in squamous metaplasia in clearly demarcated fields. These fields are the main salient morphologic characteristic in cervical intraepithelial neoplasia and can be recognized colposcopically as well as histomorphologically. The precise mechanism for the development of separate, well-delineated fields in HPV-related intraepithelial neoplasia and the variable susceptibility of stem or reserve cells for different HPV genotypes remains unsolved. In cervical carcinogenesis, the link between formal pathogenesis apparent as colposcopic and histomorphologic changes and the causal pathogenesis of HPV-induced genetic changes is still missing and an issue for future research.