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Journal of Clinical Microbiology, November 2008, p. 3678-3685, Vol. 46, No. 11
0095-1137/08/$08.00+0     doi:10.1128/JCM.01212-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Analysis of Human Papillomavirus Type 16 (HPV16) DNA Load and Physical State for Identification of HPV16-Infected Women with High-Grade Lesions or Cervical Carcinoma {triangledown} ,{dagger}

Maëlle Saunier,1 Sylvain Monnier-Benoit,1 Frédéric Mauny,2,3 Véronique Dalstein,4 Jenny Briolat,4 Didier Riethmuller,1 Bernadette Kantelip,1,5 Elisabeth Schwarz,6 Christiane Mougin,1 and Jean-Luc Prétet1*

EA 3181, IFR 133, Université de Franche-Comté, Rue Ambroise Paré, 25000 Besançon, France,1 Département d'Informations Médicales (DIM), Centre Hospitalier Universitaire, 25000 Besançon, France,2 UMR 6249 CNRS/Université de Franche-Comté Chrono-environnement, 25030 Besançon, France,3 CHU Reims, Hôpital Maison Blanche, Laboratoire Pol Bouin, INSERM UMR-S 903, Université de Reims Champagne-Ardenne, UFR Médecine, 51092 Reims, France,4 Service d'Anatomopathologie, Hôpital Jean Minjoz, 25000 Besançon, France,5 DKFZ F030, D-69120 Heidelberg, Germany6

Received 26 June 2008/ Returned for modification 6 August 2008/ Accepted 8 September 2008

Integration of human papillomavirus (HPV) DNA into the host cell genome is a frequent event in cervical carcinogenesis, even though this phenomenon does not seem to be mandatory for cervical cancer development. Our objective was to describe the load and physical state of HPV type 16 (HPV16) DNA in a series of cervical samples representative of the natural history of cervical cancer. We used a combination of three real-time PCR assays targeting E6, E2, and albumin genes to calculate HPV16 load (E6 and albumin) and the E2/E6 ratio as a surrogate of integration. This method was applied to 173 HPV16-positive cervical samples. Results show that viral load increases with the lesion grade (from 102 HPV16 DNA copies per 103 cells in normal samples up to 56,354 copies per 103 cells in cancers), while E2/E6 ratio decreases (from 1 in normal samples down to 0.36 in cancers). We propose that, according to this technique, an HPV16 viral load of higher than 22,000 copies/103 cells or an E2/E6 ratio of lower than 0.50 allows the identification of women with prevalent high-grade lesions or worse with a high specificity. In conclusion, both viral load and E2/E6 ratio, used in combination with an appropriate cutoff value, are suitable to screen women with prevalent cervical intraepithelial neoplasia grade 2 or 3 or cancer. Therefore, these assays would be useful in addition to routine HPV testing to more accurately identify women with (pre)cancerous lesions.

* Corresponding author. Mailing address: Laboratoire de Biologie Cellulaire et Moléculaire, IFR 133, Université de Franche-Comté, Centre Hospitalier Universitaire, Boulevard A. Fleming, 25030 Besançon cedex, France. Phone: 33.3.81.66.91.12. Fax: 33.3.81.66.83.42. E-mail: jean_luc.pretet{at}univ-fcomte.fr

{triangledown} Published ahead of print on 17 September 2008.

{dagger} This work is dedicated to the memory of Jean-Gérard Guillet.

Journal of Clinical Microbiology, November 2008, p. 3678-3685, Vol. 46, No. 11
0095-1137/08/$08.00+0     doi:10.1128/JCM.01212-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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