Open AccessChanges in type‐specific human papillomavirus load predict progression to cervical cancer
Author(s) -
Depuydt Christophe E.,
Criel Arnold M.,
Benoy Ina H.,
Arbyn Marc,
Vereecken Annie J.,
Bogers Johannes J.
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01631.x
Subject(s) - viral load , cervical intraepithelial neoplasia , cervical cancer , hpv infection , medicine , immunology , cancer , papillomaviridae , human papillomavirus , virology , virus , biology , oncology
Persistent high‐risk human papillomavirus ( HPV ) infection is strongly associated with the development of high‐grade cervical intraepithelial neoplasia or cancer ( CIN 3+). 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 CIN 3+ ( 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 CIN 3+ 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 CIN 3+, 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 CIN 3+ 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.