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The impact of epithelial biomarkers, local immune response and human papillomavirus genotype in the regression of cervical intraepithelial neoplasia grades 2–3
  1. Irene Tveiterås Øvestad1,5,
  2. Einar Gudlaugsson1,5,
  3. Ivar Skaland1,
  4. Anais Malpica3,4,
  5. Ane Cecilie Munk1,2,5,
  6. Emiel A M Janssen1,
  7. Jan P Baak1,5
  1. 1Department of Pathology, Stavanger University Hospital, Stavanger, Norway
  2. 2Department of Gynecology, Stavanger University Hospital, Stavanger, Norway
  3. 3Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  4. 4Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  5. 5The Gade Institute, Medical-Odontologic Faculty, University of Bergen, Bergen, Norway
  1. Correspondence to Professor Dr J P A Baak, Department of Pathology, Stavanger University Hospital, Box 8100, Stavanger 4068, Norway; jpabaak{at}


Background and aims 15–30% of cases of cervical intraepithelial neoplasia grades 2–3 (CIN2–3) detected in punch biopsies regress spontaneously (ie, show CIN1 or less in the follow-up cone). Epithelial retinoblastoma protein (pRb), tumour suppressor protein (p53), HPV genotype and immunoreactive cells have been reported to be helpful in predicting regression but their interaction in regression prediction is unknown.

Material and methods 55 cases of CIN2–3 in cervical biopsies with subsequent cervical cones were studied retrospectively to assess how epithelial biomarkers, immunoreactive cells (with immunohistochemistry) and high-risk (hr) HPV genotypes (by the AMPLICOR and linear array tests) prognostically interact with epithelial pRb and p53.

Results 18% of CIN2–3s regressed (median biopsy–cone interval of 12.0 weeks, range 5.0–34.1 weeks). CIN2–3s that regressed had higher epithelial pRb and p53, lower stromal CD25+ and CD138+, and higher CD8 cells than persistent lesions. They also had higher ratios of CD4+/CD25+ and CD8+/CD25 in stroma and epithelium. HPV16 correlated with low pRb and low CD8+. With multivariate analysis a combined high ratio of CD8+/CD25+ in the stroma, high epithelial pRb and p53 expression had independent value to predict the regression.

Conclusions CIN2–3 lesions with a non-hrHPV16 infection, high ratios of stromal CD8+/CD25+ and high epithelial expression of pRb or p53 are associated with spontaneous regression.

  • Cervix
  • HPV
  • immunohistochemistry
  • immunopathology
  • molecular pathology

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  • Funding Helse Vest, project #507030 and the Stavanger University Hospital #2009/632.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Regional Medical Ethics Committee of Helse Vest, Norway (#205/06), the Norwegian Social Science Data Service (#5909/06) and the Norwegian Data Inspectorate (#11512).

  • Provenance and peer review Not commissioned; externally peer reviewed.