title: Changes in type-specific human papillomavirus load predict progression to cervical cancer.
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.
authors.affiliation: RIATOL, Department of Molecular Diagnostics, Sonic Healthcare Benelux, Antwerp, Belgium. christophe.depuydt@riatol.be
authors.forename: Christophe E
authors.initials: CE
authors.lastname: Depuydt
authors.forename: Arnold M
authors.initials: AM
authors.lastname: Criel
authors.forename: Ina H
authors.initials: IH
authors.lastname: Benoy
authors.forename: Marc
authors.initials: M
authors.lastname: Arbyn
authors.forename: Annie J
authors.initials: AJ
authors.lastname: Vereecken
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Bogers
mesh_terms: D002584:Cervix Uteri / Q000821:virology; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000145:classification* / Q000502:physiology*; D030361:Papillomavirus Infections / Q000821:virology*; D016133:Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D019562:Viral Load; D014779:Virus Replication; D002578:Uterine Cervical Dysplasia / Q000821:virology*
chemical_list: D004279:DNA, Viral; D009856:Oncogene Proteins, Viral