Human papillomavirus oncogene mRNA testing for the detection of anal dysplasia in HIV-positive men who have sex with men

Silling, Steffi; Kreuter, Alexander; Hellmich, Martin; Swoboda, Jochen; Pfister, Herbert; Wieland, Ulrike

doi:10.1016/j.jcv.2011.12.029

« Previous Next »Journal of Clinical Virology
Volume 53, Issue 4 , Pages 325-331, April 2012

Human papillomavirus oncogene mRNA testing for the detection of anal dysplasia in HIV-positive men who have sex with men

Steffi Silling
- Institute of Virology, National Reference Center for Papilloma- and Polyomaviruses, University of Cologne, Fuerst-Pueckler-Strasse 56, 50935 Koeln, Germany
Alexander Kreuter
- Department of Dermatology, Ruhr University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany
Martin Hellmich
- Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Kerpener Strasse 62, 50937 Koeln, Germany
Jochen Swoboda
- Institute of Cytology, Koblenzer Strasse 121–123, 53177 Bonn, Germany
Herbert Pfister
- Institute of Virology, National Reference Center for Papilloma- and Polyomaviruses, University of Cologne, Fuerst-Pueckler-Strasse 56, 50935 Koeln, Germany
Ulrike Wieland
- Institute of Virology, National Reference Center for Papilloma- and Polyomaviruses, University of Cologne, Fuerst-Pueckler-Strasse 56, 50935 Koeln, Germany
- Corresponding author. Tel.: +49 0 221 478 3901; fax: +49 0 221 478 3904.

Received 2 November 2011; received in revised form 22 December 2011; accepted 23 December 2011. published online 20 January 2012.

Abstract

Background

Anal human papillomavirus (HPV) infection and anal dysplasia are frequent in HIV-positive men who have sex with men (HIV+MSM), and progression of low-grade (LSIL) to high-grade squamous intraepithelial lesions (HSIL) or anal cancer (AC) occurs faster than in HIV-negative individuals. High-risk (HR)-HPV-E6/E7 oncogene mRNA testing has a higher specificity and a higher positive predictive value (PPV) than HR-HPV-DNA testing for detecting high-grade cervical lesions.

Objective

To evaluate the diagnostic accuracy of the NucliSENS-EasyQ HPV1.1 E6/E7-mRNA-assay for the detection of anal dysplasia in HIV+MSM.

Study design

289 intraanal swabs from HIV+MSM participating in a screening program that included anal cytology, high-resolution anoscopy and histology were analyzed. HR-HPV-DNA detection was performed by PCR and hybridization using a bead-based multiplex genotyping assay. E6/E7-mRNA detection of HR-HPV-types 16, 18, 31, 33 and 45 was performed using the NucliSENS-EasyQ assay.

Results

269 swabs had valid results in both test formats (111 normal, 10 ASCUS, 105 LSIL, 42 HSIL, 1 AC). For the detection of LSIL+(LSIL+HSIL+cancer) sensitivity, specificity, negative predictive value (NPV) and PPV were 80.4%, 26.4%, 52.5%, and 57.2% for HR-HPV-DNA testing, respectively, compared to 75.7%, 57.9%, 66.0% and 68.7% for E6/E7-mRNA testing. The respective values for the detection of HSIL/cancer were 95.3%, 26.1%, 96.7%, 19.7% for HR-HPV-DNA and 95.3%, 46.0%, 98.1%, 25.2% for E6/E7-mRNA detection.

Conclusion

Compared to HR-HPV-DNA detection, E6/E7-mRNA testing has an increased specificity (approximately two-fold), similar sensitivity and higher NPV and PPV for the detection of low- and high-grade anal dysplasia in HIV+MSM.

Abbreviations: AC, anal cancer, AIN, anal intraepithelial neoplasia, ASCUS, atypical squamous cells of undetermined significance, CI, confidence interval, CIN, cervical intraepithelial neoplasia, dl, detection limit, HIV, human immunodeficiency virus, HIV+MSM, HIV-positive men who have sex with men, HPV, human papillomavirus, HR, high-risk, HRA, high-resolution anoscopy, HSIL, high-grade squamous intraepithelial lesion, LR, low-risk, LSIL, low-grade squamous intraepithelial lesion, NASBA, nucleic acid sequence based amplification, nd, not done, NPV, negative predictive value, PCR, polymerase chain reaction, PPV, positive predictive value, vs., versus