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%). Conclusion: 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.