These authors contributed equally to this work.
1096-9896/asset/PATH_left.gif?v=1&s=f8845e760fcc5be3e3baa6119dcc01c077e3db22)
1096-9896/asset/PATH_right.gif?v=1&s=86062495907b9532cd169b5a6605dac7fd14f581)
Original Paper
One virus, one lesion—individual components of CIN lesions contain a specific HPV type†
Article first published online: 17 FEB 2012
DOI: 10.1002/path.3970
Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Additional Information
How to Cite
Quint, W., Jenkins, D., Molijn, A., Struijk, L., van de Sandt, M., Doorbar, J., Mols, J., Van Hoof, C., Hardt, K., Struyf, F. and Colau, B. (2012), One virus, one lesion—individual components of CIN lesions contain a specific HPV type. J. Pathol., 227: 62–71. doi: 10.1002/path.3970
- †
Conflict of interest statement: BC, FS, KH, and JM, are employees of GlaxoSmithKline Biologicals s.a. (GSK). DJ was an employee of GSK at the time of the study start and is currently a consultant for GSK in the field of HPV. BC, FS, and KH own shares and options to shares in GSK. BC and WQ are designated inventors on a variety of patents owned by GSK. CVH has received honoraria from GSK for her participation in the study. WQ, AM, LS, MVDS, and JD received grants in the frame of research collaboration with GSK.
- §
These authors contributed equally to this work.
Publication History
- Issue published online: 4 APR 2012
- Article first published online: 17 FEB 2012
- Accepted manuscript online: 30 NOV 2011 03:37AM EST
- Manuscript Accepted: 4 NOV 2011
- Manuscript Revised: 1 NOV 2011
- Manuscript Received: 23 AUG 2011
- Abstract
- Article
- References
- Cited By
Keywords:
- laser capture micro-dissection;
- PCR;
- biopsy;
- HPV genotype;
- multiple HPV infections
Abstract
In 20–40% of cervical intra-epithelial neoplasia (CIN) and in 4–8% of cervical carcinoma tissue specimens, multiple HPV genotypes have been detected. Whole tissue section (WTS) PCR does not determine how the individual types relate causally to complex and multiple CIN. Our objective was to determine whether laser capture micro-dissection (LCM) with HPV PCR genotyping (LCM-PCR) could accurately recover type-specific HPV DNA from epithelial cells in individual areas of CIN and normal epithelium, and whether one or more viruses are present in one lesion. For that, histologically selected samples of CIN and normal epithelium were isolated by LCM and analysed by the SPF10 PCR/LiPA25 (version 1) HPV genotyping system for 25 HPV genotypes. HPV genotypes detected in 756 areas of CIN (grade 1, 2 or 3) by LCM-PCR were compared with results obtained by WTS-PCR in 60 cases (74 biopsies). We showed that when a single HPV type is detected by WTS-PCR, that type was almost always (94%; 29/31) recovered by LCM-PCR from CIN. When multiple HPV types were present by WTS-PCR, their distribution within histological sections could be mapped by LCM-PCR. Association of a single HPV type with a discrete area of CIN was found for 93% (372/399) of LCM fragments analysed by PCR. We found colliding CIN lesions associated with separate HPV types and only 62% (61/99) of HPV types detected by WTS-PCR were found in CIN by LCM-PCR. Therefore, the LCM-PCR technique was found very accurate for high-resolution HPV genotyping and for assigning an individual HPV type to an area of CIN. At LCM level, in cervical biopsy sections with multiple HPV infections, the relation between HPV types and CIN lesions is often complex. Almost every HPV type found in CIN by LCM-PCR is associated with a biological separate independent CIN lesion—one virus, one lesion. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.