Peter Hillemanns1, Xiuli Wang. 1. Department of Obstetrics and Gynecology of the University of Munich-Grosshadern, Germany. Hillemanns.Peter@mh-hannover.de
Abstract
OBJECTIVE: Vulvar intraepithelial neoplasia (VIN) is a premalignant disease of the lower genital tract. The increased occurrence of high-risk human papillomavirus (HPV) infection seems to be associated with the increasing frequency of VIN. Integration of HPV DNA into host chromosome has been hypothesized to be a critical step in the carcinogenesis of cervical neoplasia resulting in altered expression of two viral transforming genes E6 and E7. METHOD: We analyzed HPV-16 and HPV-18 DNA, and integrated transcripts of HPV-16 and HPV-18 genomes in 30 VIN cases with 53 lesions using a PCR-based protocol for the amplification of papillomavirus oncogene transcripts (APOT). RESULT: 24 of 30 VIN lesions (80%) harbored HPV-16 (in 23 cases) and HPV-18 DNA. Integration of HPV-16 and HPV-18 genome was observed in eight (38.1%) of 21 HPV-16/18 positive VIN III cases. All eight VIN were multifocal and had multicentric disease (CIN/VAIN) including one case that progressed to vulvar carcinoma. Five of eight lesions were found to have E7 specific viral-cellular fusion transcripts only, two of eight showed E7-E4 viral-cellular fusion transcripts, and one of eight had both episomally derived and E7-E4 viral-cellular fusion transcripts. In 10 (83.3%) of 12 multifocal VIN III patients, all specimens derived from the same patient harbored the same HPV type and HPV transcript pattern suggesting monoclonality. CONCLUSION: HPV-16 is the most prevalent type among VIN II/III. HPV-16 and HPV-18 DNA integration into host cell genome seems to be related to the progression stage of vulvar dysplasia and, therefore, may be necessary for development of HPV-associated invasive vulvar carcinoma.
OBJECTIVE:Vulvar intraepithelial neoplasia (VIN) is a premalignant disease of the lower genital tract. The increased occurrence of high-risk human papillomavirus (HPV) infection seems to be associated with the increasing frequency of VIN. Integration of HPV DNA into host chromosome has been hypothesized to be a critical step in the carcinogenesis of cervical neoplasia resulting in altered expression of two viral transforming genes E6 and E7. METHOD: We analyzed HPV-16 and HPV-18 DNA, and integrated transcripts of HPV-16 and HPV-18 genomes in 30 VIN cases with 53 lesions using a PCR-based protocol for the amplification of papillomavirus oncogene transcripts (APOT). RESULT: 24 of 30 VIN lesions (80%) harbored HPV-16 (in 23 cases) and HPV-18 DNA. Integration of HPV-16 and HPV-18 genome was observed in eight (38.1%) of 21 HPV-16/18 positive VIN III cases. All eight VIN were multifocal and had multicentric disease (CIN/VAIN) including one case that progressed to vulvar carcinoma. Five of eight lesions were found to have E7 specific viral-cellular fusion transcripts only, two of eight showed E7-E4 viral-cellular fusion transcripts, and one of eight had both episomally derived and E7-E4 viral-cellular fusion transcripts. In 10 (83.3%) of 12 multifocal VIN III patients, all specimens derived from the same patient harbored the same HPV type and HPV transcript pattern suggesting monoclonality. CONCLUSION:HPV-16 is the most prevalent type among VIN II/III. HPV-16 and HPV-18 DNA integration into host cell genome seems to be related to the progression stage of vulvar dysplasia and, therefore, may be necessary for development of HPV-associated invasive vulvar carcinoma.
Authors: E A Klimov; V V Sobolev; N A Batashkov; Z G Kokaeva; A V Tretiakov; Z A Nevozinskaya; I M Korsunskaya; T N Sukhova; O E Evina; A Z Khashukoeva Journal: Bull Exp Biol Med Date: 2022-05-02 Impact factor: 0.804
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