Changes in type‐specific human papillomavirus load predict progression to cervical cancer |
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Authors: | Christophe E. Depuydt Arnold M. Criel Ina H. Benoy Marc Arbyn Annie J. Vereecken Johannes J. Bogers |
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Affiliation: | 1. RIATOL, Department of Molecular Diagnostics, Sonic Healthcare Benelux, , Antwerp, Belgium;2. Unit of Cancer Epidemiology, Scientific Institute of Public Health, , Brussels, Belgium;3. Laboratory for Cell Biology and Histology, University of Antwerp, , Antwerp, Belgium |
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Abstract: | Persistent high-risk human papillomavirus (HPV) infection is strongly associated with the development of high-grade cervical intraepithelial neoplasia or cancer (CIN3+). However, HPV infection is common and usually transient. Viral load measured at a single time-point is a poor predictor of the natural history of HPV infection. The profile of viral load evolution over time could distinguish HPV infections with carcinogenic potential from infections that regress. A case-cohort natural history study was set-up using a Belgian laboratory database processing more than 100,000 liquid cytology specimens annually. All cytology leftovers were submitted to real-time PCR testing identifying E6/E7 genes of 17 HPV types, with viral load expressed as HPV copies/cell. Samples from untreated women who developed CIN3+ (n = 138) and women with transient HPV infection (n = 601) who contributed at least three viral load measurements were studied. Only single-type HPV infections were selected. The changes in viral load over time were assessed by the linear regression slope for the productive and/or clearing phase of infection in women developing CIN3+ and women with transient infection respectively. Transient HPV infections generated similar increasing (0.21 copies/cell/day) and decreasing (−0.28 copies/cell/day) viral load slopes. In HPV infections leading to CIN3+, the viral load increased almost linearly with a slope of 0.0028 copies/cell/day. Difference in slopes between transient infections and infections leading to CIN3+ was highly significant (P < .0001). Serial type-specific viral load measurements predict the natural history of HPV infections and could be used to triage women in HPV-based cervical cancer screening. |
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Keywords: | Viral doubling time virologic model cervical intraepithelial neoplasia liquid‐based cytology leftover real‐time quantitative PCR |
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