Integration of HPV-16 and HPV-18 DNA in vulvar intraepithelial neoplasia.
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Hillemanns
Peter
P
Department of Obstetrics and Gynecology of the University of Munich-Grosshadern, Germany. Hillemanns.Peter@mh-hannover.de
Wang
Xiuli
X
D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000235:genetics / Q000821:virology*; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D052161:Human papillomavirus 18 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics / Q000821:virology; D014158:Transcription, Genetic; D016662:Virus Integration / Q000235:genetics; D014846:Vulvar Neoplasms / Q000235:genetics / Q000821:virology*
D004279:DNA, Viral