Update on the relation of herpesvirus hominis type II to carcinoma of the cervix.

Abstract

Animals studies are described that investigate which cofactors influence the progression of herpesvirus hominis type 2 (HVH-2)-induced atypia of the cervical epithelium to malignancy. Female Wistar rats weighing 150 g were used for all experiments. 17 groups of animals were studied. The control series consisted of 7 groups. Statistical analysis of the data was undertaken using 2 standard tests for nonparametric analysis of variance. All animals inoculated with virus had positive cervico-vaginal HVH-2-specific immunofluorescence results. For the majority of the control groups 1 through 7 no significant changes in the cells of the cervical epithelium were detected. The combined regimens of azathioprine and stilbestrol dipropionate induced only mild hyperplasia of the basal cells. In the cases exposed to virus groups 8 through 17 there was evidence of atypical changes within the cervical epithelium. Most changes amounted to basal cell hyperplasia and metaplasia. The more severe atypia that developed constituted dysplasia where there was evidence of variations in orientation and location of cells within the zones of the cervical epithelium together with variations in size shape and staining intensity of individual nuclei. Despite the considerable duration of certain of the treatments there was no evidence of carcinoma in situ or of invasive carcinoma. The data presented support earlier evidence that HVH-2 influences the susceptibility of cervical cells to undergo atypical change in this model. It is likely that multiple etiologic factors influence cervical carcinogenesis and that HVH-2 functions as an etiologic agent to initiate the multistep process that proceeds as far as dysplasia. Progression from the preinvasive type of lesion was not influenced by any of the complementary treatments used. The epithelial sections from the group exposed to virus and a mixed sperm population did display the greatest degree of atypical change with regard to extent and severity of dysplasia. A direct progression to carcinoma in situ or invasive carcinoma did not develop.