High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease

Authors

  • Patti E. Gravitt,

    Corresponding author
    1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
    2. Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
    • Departments of Epidemiology and Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., E6535, Baltimore, MD 21205, USA
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    • Fax: +410-955-1383.

    • These first two authors contributed equally to this work.

  • Melinda Butsch Kovacic,

    1. Division of Cancer Epidemiology and Genetics, Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, Rockville, MD
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    • These first two authors contributed equally to this work.

  • Rolando Herrero,

    1. Proyecto Epidemiologico Guanacaste, Fundacion INCIENSA, San Jose, Costa Rica
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  • Mark Schiffman,

    1. Division of Cancer Epidemiology and Genetics, Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, Rockville, MD
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  • Concepcion Bratti,

    1. Proyecto Epidemiologico Guanacaste, Fundacion INCIENSA, San Jose, Costa Rica
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  • Allan Hildesheim,

    1. Division of Cancer Epidemiology and Genetics, Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, Rockville, MD
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  • Jorge Morales,

    1. Proyecto Epidemiologico Guanacaste, Fundacion INCIENSA, San Jose, Costa Rica
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  • Mario Alfaro,

    1. Proyecto Epidemiologico Guanacaste, Fundacion INCIENSA, San Jose, Costa Rica
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  • Mark E. Sherman,

    1. Division of Cancer Epidemiology and Genetics, Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, Rockville, MD
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  • Sholom Wacholder,

    1. Division of Cancer Epidemiology and Genetics, Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, Rockville, MD
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  • Ana-Cecilia Rodriguez,

    1. Proyecto Epidemiologico Guanacaste, Fundacion INCIENSA, San Jose, Costa Rica
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  • Robert D. Burk

    1. Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY
    2. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY
    3. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
    4. Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY
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Abstract

Cervicovaginal human papillomavirus (HPV) viral load has been purported as a potential marker for the detection of high-grade cervical intraepithelial neoplasia or cancer (≥CIN2). To examine disease association with type-specific viral load for the full-range of anogenital HPV infections, we conducted cross-sectional and prospective analyses of ∼2,000 HPV-infected women from a 10,000-woman population-based study in Guanacaste, Costa Rica with 7 years of follow-up. Cervical specimens were tested for >40 HPV types using a MY09/MY11 L1 consensus primer PCR method with type-specific dot blot hybridization and PCR signal intensity as a measure of viral load. A positive association was observed between prevalent ≥CIN2 and high viral load compared to low viral load for women with baseline single HPV16 infections (OR = 19.2, 95% CI = 4.4–83.2) and single non-16 carcinogenic infections (OR = 9.2, 95% CI = 2.1–39.9). Inclusion of women with multiple HPV types did not substantially change these associations. In prospective follow-up, only women infected with HPV16 alone (OR = 27.2, 95% = 3.5–213.5) had a strong association between high viral load and incident ≥CIN2; non-16 carcinogenic high viral load was not associated with incident ≥CIN2 (OR = 0.7, 95% CI = 0.2–1.9). Single noncarcinogenic type viral load was not associated with increased risk of prevalent or incident ≥CIN2 (OR = 1.2 and 1.1, respectively). In conclusion, carcinogenic high viral load was associated with prevalent ≥CIN2; however HPV16 was uniquely associated with incident ≥CIN2. The extent to which these observations can be translated into clinical practice must be rigorously examined in the context of the method of viral load measurement and the type-specific differences observed for incident ≥CIN2. © 2007 Wiley-Liss, Inc.

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