The process of HPV infection leading to the development of condyloma acuminatum has two perspectives: one perspective suggests that it is due to active proliferation of basal cells; the other perspective, however, suggests that the speed of basal cell proliferation is normal, but due to delayed cellular maturation, the epidermal cells cannot mature and keratinize in time for shedding, leading to cell accumulation presenting a "proliferative-like" change.
Some scholars have observed the entire process of gene transcription, tissue changes, and the occurrence of condyloma acuminatum after HPV infection in experiments. Stoler et al. infected human foreskin tissue with HPV type 11 and transplanted it under the renal capsule of nude mice. Thereafter, they took small amounts of xenograft living tissue every two weeks for a total of 14 weeks. The collected living tissues were fixed with formalin, embedded in paraffin, sectioned continuously, and observed under an optical microscope for morphological changes. They also used immunohistochemical methods to detect HPV antigens and performed in situ hybridization with 3H-labeled RNA probes to detect viral DNA replication and the transcription of several major mRNAs.
Results showed that by the fourth week post-transplantation, the first appearance of E4 and E5 transcription occurred. By the sixth to eighth week, other early region genes also underwent transcription. In the sixth week, the xenograft underwent drastic changes with cell proliferation, viral DNA replication, and vigorous transcription of E region and L region mRNAs until reaching a plateau phase. By the tenth to twelfth week, experimental condyloma acuminatum had become indistinguishable from naturally occurring condyloma acuminatum both in appearance and histology, showing thickening of the epidermal spinous layer, obvious clear keratohyaline granules in the granular layer, vacuolated cells in the spinous and granular layers, and some visible basophilic nuclear inclusions. These results indicate that the high cell proliferation and morphological characteristics of condyloma acuminatum are direct results of viral gene activity. The transcription of the E region of HPV11 increased continuously with the cell survival period and cell differentiation throughout the entire experimental process, which differs from other DNA viruses, especially with the mRNA encoding E4 and E5 maintaining relatively abundant levels. Conversely, viral DNA replication, synthesis of L region mRNA, and production of HPV antigens were limited to well-differentiated keratinocytes in the epidermis, leading some scholars to speculate that there might be a keratinocyte-specific factor necessary for HPV proliferation.