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

SonjeHPV16 genotype, p16/Ki-67 dual staining and koilocytic morphology as potential predictors of the clinical outcome for cervical low-grade squamous intraepithelial lesions 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 HPVpositive 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.

Triage of LSIL/ASC-US with p16/Ki-67 dual staining and human papillomavirus testing: a 2-year prospective study

“…This highlights the lower sensitivity of p16/Ki‐67 compared with HPV DNA testing. Although, sensitivity for p16/Ki‐67 in the current study is similar to previous studies . Generally, PPV appeared low, this is as a result of the low prevalence of CIN3 in this population (10%) and is in line with other studies showing a similar prevalence of CIN3 .…”

“…A limitation of this study is that it focused on a population of women attending colposcopy on the bases of repeat minor cytology rather than a single ASC‐US or LSIL, where a secondary test would be applied. However, sensitivity in the present study remains consistent with previous studies . While a large number of samples were excluded based on low cellularity this is likely because of the fact two or more tests were performed on the samples prior to the ThinPrep ® slide been made.…”

Presence of koilocytosis in low‐grade smears of high‐risk HPV‐positive women is a negative predictor for cervical intraepithelial neoplasia grade 3 or more

“…Koilocytosis was seen in 62% of CIN1 and was significantly associated with a lower likelihood of progression. Vrdoljak‐Mozetic et al found that non‐koilocytic HPV 16‐positive cases in LSIL cytology showed a progression rate of 50% while this was only 10.1% for koilocytic non‐16 HPV‐positive cases. Alves de Sousa et al also studied the cytopathic effects of HPV infection in relation to diagnosis of CIN2 and CIN3.…”

Deciphering the Multifactorial Susceptibility of Mucosal Junction Cells to HPV Infection and Related Carcinogenesis

“…Low-risk HPVs (mainly HPV6 and 11) are typically related to condylomata acuminata (genital warts) development and viral cytopathic effect [51,52]. In contrast, carcinogenic (high-risk) strains are less frequently associated to koilocytic morphology or virion production [52,53]. In addition to the viral component, recent findings support that the nature of the epithelial cells (basal keratinocytes versus SC junction cells) originally infected by HPV also considerably influences the appearance of CIN.…”