Physical state and viral load as predictive biomarkers for persistence and progression of HPV16-positive cervical lesions: results from a population based long-term prospective cohort study

Manawapat, Anna, Stubenrauch, Frank, Russ, Rainer, Munk, Christian, Krüger Kjaer, Susanne, and Iftner, Thomas (2012) Physical state and viral load as predictive biomarkers for persistence and progression of HPV16-positive cervical lesions: results from a population based long-term prospective cohort study. American Journal of Cancer Research, 2 (2). ajcr0000095. pp. 192-203.

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Abstract

Persistent infection with a high risk (hr) human papillomavirus (HPV) has been established as the main cause of cervical cancer and high-grade cervical intraepithelial neoplasia (CIN3). Because most infections are transient, testing for hrHPV lacks specificity and has a low positive predictive value. It has been suggested that additional parameters like viral load and physical status of the viral genome could improve the effectiveness of HPV-based screening. We investigated the association between HPV16 viral load and physical state with viral persistence or risk of incident CIN3 or worse in a population-based prospective cohort study comprising 8656 women (20-29 years). All participants had two gynecological examinations two years apart and were followed through the nationwide Danish Pathology Data Bank (median follow-up: 12.9 yrs). Seventynine cervical swabs from women with a persistent HPV16 infection were available for analysis. For comparison we selected a random age-matched sample of transiently HPV16 infected women (N=91). Persistently infected women with incident CIN3 or cancer (CIN3+; N=31) were compared to women with normal cytology during follow up (non-progressors; N=39). Quantitative real-time PCR for HPV16E6, E2 and IFNb1 was done to determine the HPV16 viral load and the E2/E6 ratio was used as a surrogate marker for integration. Women with normal cytology who became persistently HPV16 infected had a significantly lower HPV16 load at baseline than women who cleared the infection (median 4.72 copies/cell versus median 20.0 copies/cell, respectively; p=0.0003). There was no difference in viral load at enrollment between women who progressed to CIN3+ and women who stayed cytologically normal (p=0.85). At the second examination viral load tended to be higher in women who progressed, but the difference was not statistically significant (p=0.39). The E2/E6 ratio was shown to be lower in the persistently infected group (p<0.0001) already at the first examination, but no difference between non-progressors and CIN3+ cases was observed at any of the two examinations (p=0.61 and 0.86). Lower viral load and integration of the viral genome are predictive for the persistence of HPV16 DNA, but not for the progression of a persistent HPV16 infection to CIN3+ in women with normal cytology.

Item ID: 32607
Item Type: Article (Research - C1)
ISSN: 2156-6976
Keywords: cervical cancer, HPV, viral load, viral integration
Additional Information:

Once the paper is published, the copyright will be released by the publisher under the "Creative Commons Attribution Noncommercial License", enabling the unrestricted non-commercial use, distribution, and reproduction of the published article in any medium, provided that the original work is properly cited. If the manuscript contains a figure or table reproduced from a book or another journal article, the authors should obtain permission from the copyright holder before submitting the manuscript, and be fully responsible for any legal and/or financial consequences if such permissions are not obtained. (Copied from 'information for authors' page of the journal 9/4/14.)

Funders: Mermaid Project, Savværksejer Jeppe Juhl og Hustru Ovita Juhls Mindelegat, Danish Cancer Society
Date Deposited: 23 Apr 2014 01:28
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111799 Public Health and Health Services not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920499 Public Health (excl. Specific Population Health) not elsewhere classified @ 100%
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