Collins, S. I., Constandinou-Williams, C., Wen, K., Young, Lawrence S., Roberts, S., Murray, P. G. and Woodman, Ciaran B. J.. (2009) Disruption of the E2 Gene is a common and early event in the natural history of cervical human papillomavirus infection : a longitudinal cohort study. Cancer Research, Vol.69 (No.9). pp. 3828-3832. ISSN 0008-5472

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Abstract

Integration of high-risk human papillomavirus (HPV) types into the host-cell genome disrupts the HPV regulatory E2 protein, resulting in a loss of negative feedback control of viral oncogene expression; this disruption has been considered a critical event in the pathogenesis of cervical neoplasia, and a potential biomarker of progressive disease. However, using serial samples taken from a cohort of young women who were recruited soon after they first had sexual intercourse, we show that disruption of the E2 gene is a common and early event in the natural history of incident cervical HPV infections. The E2 gene was significantly more likely to be disrupted in women who tested positive for HPV18 in their baseline sample than in those who tested positive for HPV16 [26% versus 58%; relative risk, 2.26; 95% confidence interval (CI), 1.38–3.71; χ2, 9.23; 1 degree of freedom (df); P = 0.002]. Among women with an intact E2 gene in their baseline sample, the median time to first detection of E2 disruption was also shorter for those who tested positive for HPV18 than HPV16 (5.7 versus 10.9 months; hazards ratio, 1.93; 95% CI, 0.84–4.44; χ2, 2.49; 1 df; P = 0.11). This tendency for HPV18 to integrate early, coupled with the substantial reduction in viral load in HPV18-positive samples in which E2 is disrupted, may explain why HPV18-associated disease is often reported to be characterized by minor cytologic changes, which underestimate the severity of the underlying histologic abnormality.

Item Type:	Journal Article
Divisions:	Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Cancer Research
Publisher:	American Association for Cancer Research
ISSN:	0008-5472
Date:	1 May 2009
Volume:	Vol.69
Number:	No.9
Page Range:	pp. 3828-3832
Identification Number:	10.1158/0008-5472.CAN-08-3099
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
URI:	http://wrap.warwick.ac.uk/id/eprint/51866

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