title: Progression of cervical low grade squamous intraepithelial lesions: in search of prognostic biomarkers.
abstract: OBJECTIVE
  It has been reported that approximately 10% of low grade squamous intraepithelial lesions (LSIL) progress to high grade squamous intraepithelial lesions (HSIL) within a 2-year follow up. The factors related to lesion progression are currently unknown. The aim of the study was to identify prognostic markers of the course of LSIL. This retrospective study was designed to correlate regression, persistence and progression of biopsy-proven LSIL with patients' age, HPV genotypes and immunohistochemical expression of the main cell cycle regulating proteins: p53, pRb, p16, and Ki-67.
  
  
  METHODS
  A total of 584 consecutive patients with biopsy proven LSIL and 2-year follow-up were included in the age analysis. HPV genotyping was performed in 328 LSIL cases using the SPF10 PCR-LiPA25 (version 1), 238 LSIL cases were immunostained for Ki-67 and p16, and 101 cases were immunostained for pRb and p53.
  
  
  RESULTS
  The odds of LSIL persistence and progression were significantly higher in women 30-39, 40-49 and 50+ years old, as compared to women 20-29 years old (OR 1.89, 2.52 and 2.39, respectively). The odds of persistence and progression were higher in women infected with HPV16, 18, 33 and 52 (OR 3.5, 3.1, 3.5 and 2.9, respectively). There were no significant differences in expression of immunomarkers (p16, p53, pRB and Ki-67) between the lesions that regressed versus the lesions that persisted or progressed.
  
  
  CONCLUSIONS
  Patients 30 years of age and older have a higher risk of LSIL progression or persistence as compared to 20-29 year olds. In addition, HPV genotyping, but not the cell cycle markers, may aid in prognosis of LSIL course.
authors.affiliation: DDL Diagnostic Laboratory, Rijswijk, the Netherlands.
authors.forename: Koen D
authors.initials: KD
authors.lastname: Quint
authors.forename: Maurits N C
authors.initials: MN
authors.lastname: de Koning
authors.forename: Wim G V
authors.initials: WG
authors.lastname: Quint
authors.forename: Edyta C
authors.initials: EC
authors.lastname: Pirog
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D052685:Alphapapillomavirus / Q000235:genetics; D002453:Cell Cycle; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology; D002648:Child; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D012075:Remission, Spontaneous; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology* / Q000821:virology
chemical_list: D019394:Ki-67 Antigen; D025521:Tumor Suppressor Proteins
keywords: HPV; Ki-67; LSIL; p16; p53; pRb