Morphological transformation in vivo of human uterine cervix with papillomavirus from condylomata acuminata

Abstract

Carcinoma of the human uterine cervix has been associated with several infectious agents^1–5 including papillomaviruses^6,7. Papillomavirus group-specific antigen (GSA)^8,9 and viral particles¹⁰ have been demonstrated in human condylomata acuminata (CA) and flat warts of the uterine cervix. Cell alterations consisting of nuclear enlargement, hyperchromasia, irregularity, binucleation and cytoplasmic clearing (koilocytosis) are often interpreted as mild to moderate dysplasia¹¹. Present evidence that human papillomavirus (HPV) is responsible for the development of these lesions relies on the association of GSA⁷ and virus particles⁸ in the affected tissue, fulfilling the first two of Koch's postulates¹². Direct proof of an aetiological relationship, however, requires induction of the CA change in normal, human uterine cervix after exposure to papillomavirus. Infecting human subjects with HPV is ethically unacceptable and no satisfactory alternative systems have been defined. Also, human cell cultures do not support growth or transformation by HPV. Here we report the first demonstration of the morphological transformation of human tissues with a human papillomavirus under controlled, experimental conditions. ‘Transformation’ is used here in its literal sense to refer to a heritable morphological alteration in the.appearance of the cells. The use of this term does not indicate that the changes described are neoplastic, but they are identical to the dysplastic changes found in biopsies of uterine cervical CA. Our results demonstrate the direct involvement of CA virus in dysplastic change of human cervical tissue and indicate that the experimental system described may be useful in elucidating the contribution of human papillomaviruses to the pathogenesis of human cervical cancer.