HPV in situ hybridization signal patterns as a marker for cervical intraepithelial neoplasia progression

Gynecol Oncol. 2009 Jan;112(1):114-8. doi: 10.1016/j.ygyno.2008.09.047. Epub 2008 Nov 12.


Objective: HPV-DNA integration is one factor for malignant transformation and can be identified using in situ hybridization (ISH), where a diffuse signal represents episomal HPV and punctate, integrated. The aim is to verify if a punctate pattern could be a marker of CIN1 that progresses.

Methods: 74 CIN1 biopsies were studied. In the follow up, a second biopsy was performed and 65% showed CIN1 or no lesion (group without progression) and 35% CIN2/3 (with progression). ISH was carried out with HR-HPV GenPoint in the first biopsy looking for the positive distribution in epithelium regions (basal, intermediate, superficial) and reaction pattern (diffuse and punctate). The Mann-Whitney and Fisher tests were used to compare the groups (p<or=0.05).

Results: The mean age of patients without progression was 26 and, with progression 31 (p=0.02). ISH was positive in 22 cases, 8 with CIN2/3 in the second biopsy. The punctate signal was observed in all epithelial layers, and the mean coefficient between the number of cells with punctate and diffuse signals was 3.5 times more common in the progression group (p=0.08). The average percentage of punctate nuclei patterns in the basal region in cases without progression was 0.5% and 11% in those with progression (p=0.05). However, in superficial layer this was not correlated with progression.

Conclusion: Progression was observed in 35% of CIN1 and associated with age; 30% of the cases were positive by ISH, but must be carefully interpreted. Punctate signals were related to progression only in basal cells, identifying CIN1 with potentially aggressive behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Cell Transformation, Viral
  • Cervical Intraepithelial Neoplasia / pathology*
  • Cervical Intraepithelial Neoplasia / virology*
  • DNA, Viral / genetics
  • Disease Progression
  • Female
  • Humans
  • In Situ Hybridization
  • Middle Aged
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / virology*
  • Retrospective Studies
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / virology*
  • Virus Integration
  • Young Adult


  • DNA, Viral