HPV Implication Pattern in Coexistent HSIL/AIS Lesion.
Fumi Kawakami, Hiroe Itami, Noriko Oka, Shuho Semba, Yoshiki Mikami, Tamotsu Sudo, Chiho Ohbayashi, Hiroshi Yokozaki, Tomoo Itoh. Kobe University Hospital, Hyogo, Japan; Hyogo Cancer Center, Akashi, Hyogo, Japan; Sysmex Corporation, Kobe, Hyogo, Japan; Kobe University Graduate School of Medicine, Hyogo, Japan; Kyoto University Hospital, Japan
Background: High-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS) are premalignant uterine cervical lesions, and most of them are human papilloma virus (HPV) associated. For the last few decades a panel of theories mentioned the origin of coexistent HSIL and AIS lesion; however there are still few molecular evidences related to those theories. In this study, we examined HPV subtypes as well as the methylation status of the HPV-16 L1 gene to reveal the difference or affinity of carcinogenetic pathway between HSIL and AIS.
Design: A total of 8 HSIL and AIS lesions were removed by conization or hysterectomy. In each case, HSIL and AIS lesions were isolated individually by micro-dissection from deparaffinized tissue sections. Further, high-risk HPV (HPV-16, -18, -31, -33, -52, -58, and -35) PCR genotyping were performed. Bisulfite-treated DNA was processed to analyze HPV-16-positive cases for the methylation status at the L1 and LCR genes; after a while the methylation status within HSIL and AIS were compared by P-value of Fisher's exact test.
Results: Out of 8 cases, 6 (75%) showed same subtype of HPV in both HSIL and AIS: HPV-16, 5 cases; and HPV-18, 1 case. And then 2 (25%) cases contained different subtypes of HPV between HSIL and AIS: HPV-31 (HSIL) and HPV-18 (AIS); and HPV-52 (HSIL) and HPV-16 (AIS). Among the five cases which contained HPV-16 in both HSIL and AIS, no significant difference with one exception in the frequency of CpG island methylation status in the HPV-16 L1 region were observed; likewise only one case within 6796 genomic position was significantly methylated in HSIL compared with coexistent AIS (P = 0.0278).
Conclusions: Our finding suggests that same HPV subtype is involved in the individual carcinogenetic pathway in the majority of the cases coexistent HSIL and AIS lesions. Further more, there is no significant difference between HSIL and AIS in the methylation pattern of HPV-16 L1 gene. These facts suggest that, the two lesions largely arise from same progenitor cells in which recombination between HPV and host cell DNA is occurred. While in the minority of the cases, HSIL and AIS may arise individually with different HPV infectious background and collided with each other.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 208, Tuesday Morning