Objective To investigate the pathogenic role of high risk HPVs and genomic integration of HPV 16/18 DNA in vulvar intraepithelial neoplasia (VIN) patients. Methods Hybrid Capture HPV DNA assay and PCR were performed to detect high-risk HPVs and HPV 16/18 positive samples. Then RT-PCR, nested PCR and Southern blotting analysis were used in HPV 16/18 positive samples for the amplification and analysis of papillomavirus oncogene transcripts. Results In 32 cases of VIN patients, 24(75%) high-risk HPVs were detected, 23 were HPV 16, and only 1 was HPV 18. Genomic integration of HPV 16/18 was observed in 8 cases of VIN Ⅲ (7 HPV 16 and 1 HPV 18). Except 1 case of VIN Ⅱ, 15 of 23 HPV-16 positive specimens displayed HPV16 episomal transcripts, 7 displayed integrated transcripts. Conclusions HPV 16 is positive in most cases of VIN Ⅱ and VIN Ⅲ. Integration of HPV 16/18 oncogene only occurs in VIN Ⅲ. It is concluded that the integration of high-risk HPVs oncogene is related with the occurrence, and the development to vulvar cancer, of VIN.

OBJECTIVE: To show noninferiority of a limited-excision (resection of the dysplastic lesion only) vs. classical Large Loop Excision of the Transformation Zone (LLETZ). METHODS: In this prospective, randomized, multicenter trial, women with human papillomavirus (HPV) positive cervical intraepithelial neoplasia grade 3 were randomized into two groups (1:1). Primary outcome was the rate of negative HPV tests after 6 months, secondary outcomes included cone size, complete resection rates as well as cytological and histological results after 6 and 12 months. A sample size of 1,000 was calculated to show noninferiority of the limited-excision compared to the LLETZ group using a noninferiority margin of 5%. Enrollment was stopped after 100 patients due to slow accrual. RESULTS: Patients in the limited-excision group did not show a lower number of negative HPV tests (78% [LLETZ]−80% [limited-excision]=−2%; 90% confidence interval=−15%, 12%). The limited-excision resulted in a substantially lower cone size (LLETZ: 1.97 mL vs. limited-excision: 1.02 mL; p < 0.001) but higher numbers of involved margins (LLETZ: 8% vs. limited-excision: 20%). Although postoperative cytological results slightly differed, histological results were similar in both groups. One limited-excision patient received immediate re-conisation, whereas one patient in each group was scheduled for re-conisation after 6 months. CONCLUSION: The limited-excision could represent a promising option to reduce the surgical extent of conisations while maintaining oncological safety. The trial was not sufficiently powered to reach statistical significance due to early termination. Nevertheless, the study provides important insights in the feasibility of a limited-excision and could serve as a pilot study for future trials. TRIAL REGISTRATION: German Clinical Trials Register Identifier: DRKS00006169
Cervical Intraepithelial Neoplasia ; Conization ; Female ; Humans ; Multicenter Studies as Topic ; Pilot Projects ; Premature Birth ; Prospective Studies ; Sample Size