title: HPV16 genotype, p16/Ki-67 dual staining and koilocytic morphology as potential predictors of the clinical outcome for cervical low-grade squamous intraepithelial lesions.
abstract: OBJECTIVE
  To evaluate the association of human papillomavirus (HPV) 16 and non-16 genotype, p16/Ki-67 dual staining and koilocytosis and their role in the prediction of the clinical outcome of low-grade squamous intraepithelial lesion (LSIL) cytology.
  
  
  METHODS
  One hundred and fifty-five patients with LSIL were followed up and recorded as progression, persistence or regression. HPV genotyping was performed for high-risk HPV (hrHPV) DNA-positive cases. Koilocytosis was reviewed and p16/Ki-67 dual staining was performed on reprocessed conventional cytology slides.
  
  
  RESULTS
  HPV16 was the most frequent genotype found in 16.3% of cases. p16/Ki-67 dual staining was positive in 36.1% of all cases. Progression, including concurrent cervical intraepithelial lesion grade 2 or above (CIN2+), was recorded in 13.8% of cases. A statistically significant difference between progressive and non-progressive cases was shown by the following: hrHPV-positive versus hrHPV-negative (P = 0.022), HPV16-positive versus non-16 HPV-positive (P < 0.001) and p16/Ki-67-positive versus p16/Ki-67-negative (P < 0.001) cases. Cases with combined HPV16 and p16/Ki-67 positivity showed the highest progression rate (58.3%). Non-koilocytic HPV16-positive cases showed a 50% progression rate compared with 10.1% for koilocytic non-16 HPV-positive cases (P = 0.010). The sensitivity of p16/Ki-67 dual staining for the detection of CIN2+ lesions was 80%, comparable with hrHPV (85%). The specificity of p16/Ki-67 dual staining was 71% and of hrHPV 42%. The highest specificity was found for HPV16 genotype presence (91%), but with low sensitivity (50%).
  
  
  CONCLUSIONS
  HPV genotyping, p16/Ki-67 dual staining and koilocytic morphology can be useful in the prediction of clinical outcome in women initially diagnosed with LSIL cytology.
authors.affiliation: Department of Clinical Cytology, University of Rijeka, Rijeka, Croatia.
authors.forename: D
authors.initials: D
authors.lastname: Vrdoljak-Mozetič
authors.forename: M
authors.initials: M
authors.lastname: Krašević
authors.forename: D
authors.initials: D
authors.lastname: Verša Ostojić
authors.forename: S
authors.initials: S
authors.lastname: Štemberger-Papić
authors.forename: R
authors.initials: R
authors.lastname: Rubeša-Mihaljević
authors.forename: M
authors.initials: M
authors.lastname: Bubonja-Šonje
mesh_terms: D000328:Adult; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000302:isolation & purification*; D003581:Cytodiagnosis; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000302:isolation & purification*; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000302:isolation & purification / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000175:diagnosis*; D011247:Pregnancy; D011379:Prognosis; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000175:diagnosis* / Q000473:pathology; D014626:Vaginal Smears
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen
keywords: HPV genotype; LSIL; cervical cytology; clinical outcome; koilocytosis; low-grade squamous intraepithelial lesion; p16/Ki-67