Cervical Intraepithelial Neoplasia Type Research Articles

Prospective follow-up of Japanese women with cervical intraepithelial neoplasia and various human papillomavirus types

Objective: To evaluate the prevalence of genital human papillomavirus (HPV) types in cervical neoplasias and to evaluate the biological activity of individual HPV types in cervical carcinogenesis. Method: Cellular samples from 318 patients with cervical intraepithelial neoplasia (CIN) or invasive cervical carcinoma were examined for HPV DNA, using a polymerase chain reaction. Of these, 145 women with CIN grade I or II were prospectively followed to better understand the natural history of these precancerous lesions. Result: HPV DNA was detected in 88, 80 and 89%, of CIN grade I, II and III, respectively, and in 92% in invasive carcinomas. The CIN follow-up data showed a significantly higher progression rate in patients with CIN II than in cases of CIN I, and our classification of HPV types based on HPV prevalence data correlates well with the prospective follow-up data. A significantly higher progression rate was observed in HPV-negative CINs. Conclusion: Classification of HPV types according to risk to a malignant state seems to be possible. It seems that HPV negative lesions are likely to progress to a malignant state.

Detection of the Epstein-Barr virus genome in cervical neoplasia is closely related to the degree of infiltrating lymphoid cells: a polymerase chain reaction and in situ hybridization approach.

To cast light on the significance of Epstein-Barr virus (EBV) infection in cervical tumorigenesis, 44 cervical intraepithelial neoplasia (CIN) types I/II, and 70 CIN III lesions, 60 invasive squamous cell carcinomas (ISCC), and 20 normal cervical samples were investigated by polymerase chain reaction (PCR) and RNA in situ hybridization (RISH) assays. The EBV genome was detected by PCR using primers targeting the IR region in three (6.8%) of the CIN I/II, 15 (21.4%) of the CIN III and 13 (21.7%) of the ISCC lesions, while using an EBER oligonucleotide probe RISH revealed positive signals in infiltrating lymphocytes located in the cervical stroma, but not in dysplastic or tumor cells. There was a significant correlation between the presence of EBV DNA and the degree of lymphoid cell infiltration (P = 0.0223). In contrast, none of the normal cervical samples that were without inflammation demonstrated any EBV infection. Thus, the results indicated that a positive result for EBV on PCR may be simply dependent on the amount of lymphocytes in cervical stroma, suggesting that this virus does not play a major role in the etiology of cervical neoplasia.

Cervical intraepithelial neoplasia, anogenital cancer, and other cancer types in women after hospitalization for condylomata acuminata.

To investigate the possible association between condylomata acuminata and anogenital neoplasia, a cohort of 9552 women recorded as having condylomata acuminata in the Danish Hospital Discharge Register during 1977-1989 was followed through 1991 for the occurrence of cancer and cervical intraepithelial neoplasia grade III (CIN III) by linkage to the Danish Cancer Registry. Eleven cases of vulvar cancer were identified, with 0.3 expected (standardized incidence ratio [SIR], 40.1; 95% confidence interval [CI], 20.0-71.7), and there were increased risks for cervical cancer (SIR, 2.0; 95% CI, 1.3-3.0), anal cancer (SIR, 8.5; 95% CI, 0.9-30.5), and CIN III (SIR, 2.6; 95% CI, 2.3-2.9). Risks were also elevated for non-anogenital cancers, notably lung cancer (SIR, 3.8; 95% CI, 2.2-6.0). Although confounding by smoking and other factors may exist, these results support the view that condylomata acuminata are associated with an increased risk of anogenital neoplasias, particularly vulvar cancer, and emphasize that women hospitalized with these lesions should undergo thorough anal and gynecologic examinations at regular intervals.

Organotypic (raft) epithelial tissue culture system for the differentiation-dependent replication of papillomavirus

We have developed an in vitro organotypic (raft) culture system capable of reproducing the differentiation-dependent replication cycle of human papillomavirus. A dermal equivalent is made from a mixture of type I collagen and fibroblasts. Cells of a line derived from a cervical intraepithelial neoplasia type 1 (CIN-1) are placed on top of the dermal equivalent and while submerged allowed to grow to confluence. The dermal equivalent with epithelial cells on top is then lifted onto a wire grid where it remains at an air-liquid interface. From this point on the epithelial cells never come in contact with the culture media. Feeding of the epithelial cells is done by diffusion through the dermal equivalent similar to the in vivo situation. The epithelial cells under these conditions will stratify and differentiate over approximately a two week period. When an inducer of protein kinase C is added to the media our CIN-1 derived cell lines, which maintains episomal copies of a high risk human papillomavirus will biosynthesize virion. We describe in detail how to perform this procedure and provide information on how to use this system for the study of the interaction of human papillomavirus with its host tissue, squamous epithelium.