Human papillomavirus type 18 and rapidly progressing cervical intraepithelial neoplasia

Lancet. 2003 Jan 4;361(9351):40-3. doi: 10.1016/S0140-6736(03)12120-4.


Background: Human papillomavirus type 18 (HPV-18) is the second most frequent of the HPV types detected when squamous-cell cancer is diagnosed and the type most strongly associated with adenocarcinoma of the cervix. However, in cross-sectional studies, HPV-18 is rarely detected at the time of diagnosis of high-grade cervical intraepithelial neoplasia (CIN). We used a longitudinal study design to describe the occurrence of cytological abnormality after incident HPV-18 and HPV-16 infections.

Methods: The analysis was based on 1075 women aged 15-19 years, who had normal cytology and were negative for HPV at recruitment from a single family-planning clinic, and who had further follow-up. The women reattended every 6 months, and samples were taken for cytological and virological examination.

Findings: The relative risk of a cytological diagnosis of borderline nuclear abnormality after exposure to HPV-18 was 2.06 (95% CI 1.24-3.43) and that after exposure to HPV-16 was 1.99 (1.32-3.01). The relative risks of mild dyskaryosis were 3.11 (1.86-5.18) and 4.76 (3.15-7.18), and the relative risks of moderate or severe dyskaryosis were 0.80 (0.24-2.65) and 2.85 (1.36-5.97). Time to acquisition of cytological abnormality was unrelated to the infecting type (p=0.88).

Interpretation: Our findings do not support the long-held view that the reason why HPV-18 infection is under-represented at the time of diagnosis of high-grade CIN is because HPV-18-associated disease rapidly progresses through the preinvasive stages of neoplasia. We suggest that the cytological changes detected after HPV-18 infection might understate the severity of underlying disease. This feature could compromise the effectiveness of screening programmes in reducing the frequency of HPV-18-associated cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cervical Intraepithelial Neoplasia / diagnosis
  • Cervical Intraepithelial Neoplasia / pathology
  • Cervical Intraepithelial Neoplasia / virology*
  • Female
  • Humans
  • Longitudinal Studies
  • Papillomaviridae / isolation & purification*
  • Papillomaviridae / pathogenicity
  • Papillomavirus Infections / classification
  • Papillomavirus Infections / complications*
  • Severity of Illness Index
  • Tumor Virus Infections / classification
  • Tumor Virus Infections / complications*