Changes in type-specific human papillomavirus load predict progression to cervical cancer

J Cell Mol Med. 2012 Dec;16(12):3096-104. doi: 10.1111/j.1582-4934.2012.01631.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cervix Uteri / virology
  • Cohort Studies
  • DNA, Viral / analysis
  • Female
  • Humans
  • Oncogene Proteins, Viral / genetics
  • Papillomaviridae / classification*
  • Papillomaviridae / physiology*
  • Papillomavirus Infections / virology*
  • Polymerase Chain Reaction
  • Uterine Cervical Dysplasia / virology*
  • Uterine Cervical Neoplasms / virology*
  • Viral Load*
  • Virus Replication

Substances

  • DNA, Viral
  • Oncogene Proteins, Viral