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Journal of Clinical Microbiology, May 2006, p. 1755-1762, Vol. 44, No. 5
0095-1137/06/$08.00+0     doi:10.1128/JCM.44.5.1755-1762.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Human Papillomavirus Type 16 Integration in Cervical Carcinoma In Situ and in Invasive Cervical Cancer

Hugo Arias-Pulido,¹ Cheri L. Peyton,^1, Nancy E. Joste,² Hernan Vargas,^3,4, and Cosette M. Wheeler^1*

Departments of Molecular Genetics and Microbiology,¹ Department of Pathology, University of New Mexico, Health Sciences Center, School of Medicine, Albuquerque, New Mexico,² Grupo Farmacogenética del Cáncer, Dep. Farmacia, Universidad Nacional de Colombia, Bogotá, Colombia,³ Grupo de Biología Molecular Tumoral, Instituto Nacional de Cancerología, Bogotá, Colombia⁴

Received 24 October 2006/ Returned for modification 5 January 2006/ Accepted 20 February 2006

Integration of human papillomavirus type 16 (HPV-16) into the host DNA has been proposed as a potential marker of cervical neoplastic progression. In this study, a quantitative real-time PCR (qRT-PCR) was used to examine the physical status of HPV-16 in 126 cervical carcinoma in situ and 92 invasive cervical cancers. Based on criteria applied to results from this qRT-PCR assay, HPV-16 was characterized in carcinoma in situ cases as episomal (61.9%), mixed (i.e., episomal and integrated; 29.4%), and integrated (8.7%) forms. In invasive cervical cancer samples, HPV-16 was similarly characterized as episomal (39.1%), mixed (45.7%), and integrated (15.2%) forms. The difference in the frequency of integrated or episomal status estimated for carcinoma in situ and invasive cervical cancer cases was statistically significant (P = 0.003). Extensive mapping analysis of HPV-16 E1 and E2 genes in 37 selected tumors demonstrated deletions in both E1 and E2 genes with the maximum number of losses (78.4%) observed within the HPV-16 E2 hinge region. Specifically, deletions within the E2 hinge region were detected most often between nucleotides (nt) 3243 and 3539. The capacity to detect low-frequency HPV-16 integration events was highly limited due to the common presence and abundance of HPV episomal forms. HPV-16 E2 expressed from intact episomes may act in trans to regulate integrated genome expression of E6 and E7.

Present address: Department of Zoology, Oregon State University, Corvallis, Oreg.

Present address: Grupo Farmacogenética del Cáncer, Dep. Farmacia, Universidad Nacional de Colombia, Bogotá, Colombia.

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