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Journal of Clinical Microbiology, August 2008, p. 2595-2604, Vol. 46, No. 8
0095-1137/08/$08.00+0     doi:10.1128/JCM.00824-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Papillomavirus Genotype Specificity of Hybrid Capture 2{triangledown} ,{dagger}

Philip E. Castle,1* Diane Solomon,2 Cosette M. Wheeler,3 Patti E. Gravitt,4 Sholom Wacholder,1 and Mark Schiffman1

Divisions of Cancer Epidemiology and Genetics,1 Cancer Prevention, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892,2 Departments of Molecular Genetics and Microbiology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center, School of Medicine, University of New Mexico, Albuquerque, New Mexico 87131,3 Departments of Epidemiology and Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, Maryland 212054

Received 30 April 2008/ Returned for modification 5 June 2008/ Accepted 16 June 2008

Hybrid Capture 2 (hc2), a clinical test for carcinogenic human papillomavirus (HPV) DNA, has proven to be a sensitive but only modestly specific predictor of cervical precancer and cancer risk. Some of its nonspecificity for clinical end points can be ascribed to cross-reactivity with noncarcinogenic HPV genotypes. However, the reference genotyping tests that have been used for these comparisons are also imperfect. We therefore sought to describe further the HPV genotype specificity of hc2 by comparing the hc2 results to paired results from two related PGMY09/11 L1 primer-based HPV genotyping assays: Linear Array (LA) and its prototype predecessor, the line blot assay (LBA). LA and LBA results were considered separately and combined (detection by either assay or both assays) for 37 individual HPV genotypes and HPV risk group categories (carcinogenic HPV > noncarcinogenic HPV > negative). Baseline specimens from 3,179 of 3,488 (91.5%) women referred to ALTS (a clinical trial to evaluate the management strategies for women with atypical squamous cells of undetermined significance [ASCUS] or low-grade squamous intraepithelial lesions) because of an ASCUS Papanicolaou smear were tested by all three assays. Among single-genotype infections with genotypes targeted by hc2 as detected by either PCR assay, HPV genotype 35 (HPV35) (86.4%), HPV56 (84.2%), and HPV58 (76.9%) were the most likely to test positive by hc2. Among single-genotype infections with genotypes not targeted by hc2 as detected by either assay, HPV82 (80.0%), HPV66 (60.0%) (recently classified as carcinogenic), HPV70 (59.1%), and HPV67 (56.3%) were the most likely to test positive by hc2. Among women who tested negative for carcinogenic HPV by both PCR tests and were positive for noncarcinogenic HPV by either test, 28% of women were hc2 positive. Conversely, 7.8% of all hc2-positive results in this population were due to cross-reactivity of hc2 with untargeted, noncarcinogenic HPV genotypes. In conclusion, hc2 cross-reacts with certain untargeted, noncarcinogenic HPV genotypes that are phylogenetically related to the targeted genotypes, but the degree of cross-reactivity may be less than previously reported.

* Corresponding author. Mailing address: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Room 5030, EPS MSC 7234, Bethesda, MD 20892-7234. Phone: (301) 435-3976. Fax: (301) 402-0916. E-mail: castlep{at}mail.nih.gov

{triangledown} Published ahead of print on 25 June 2008.

{dagger} Supplemental material for this article may be found at http://jcm.asm.org/.

Journal of Clinical Microbiology, August 2008, p. 2595-2604, Vol. 46, No. 8
0095-1137/08/$08.00+0     doi:10.1128/JCM.00824-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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