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. 2023 Aug 25;142(1):e2022527.
doi: 10.1590/1516-3180.2022.0527.R2.280423. eCollection 2023.

Cervical Intraepithelial Neoplasia grade 2 biopsy: Do p16INK4a and Ki-67 biomarkers contribute to the decision to treat? A cross-sectional study

Amanda Leal Ferreira  1 , Nasle Domingues Dibe  2 , Bruna Rodrigues de Paiva  3 , Elyzabeth Avvad Portari  4 , Dione Corrêa de Araújo Dock  5 , Nilma Valéria Caldeira Ferreira  6 , Saint Clair Gomes Junior  7 , Fábio Bastos Russomano  8 , Cecília Vianna de Andrade  9
Affiliations

Cervical Intraepithelial Neoplasia grade 2 biopsy: Do p16INK4a and Ki-67 biomarkers contribute to the decision to treat? A cross-sectional study

Amanda Leal Ferreira et al. Sao Paulo Med J. .

Abstract

Background: Managing cervical intraepithelial neoplasia grade 2 (CIN2) is challenging, considering the CIN2 regression rate, perinatal risks associated with excisional procedures, and insufficient well-established risk factors to predict progression.

Objectives: To determine the ability of p16INK4a and Ki-67 staining in biopsies diagnosed with CIN2 to identify patients with higher-grade lesions (CIN3 or carcinoma).

Design and setting: Cross-sectional study conducted at a referral center for treating uterine cervical lesions.

Methods: In 79 women, we analyzed the correlation of p16INK4a and Ki-67 expression in CIN2 biopsies with the presence of a higher-grade lesions, as determined via histopathology in surgical specimens from treated women or via two colposcopies and two cytological tests during follow-up for untreated women with at least a 6-month interval. The expression of these two biomarkers was verified by at least two independent pathologists and quantified using digital algorithms.

Results: Thirteen (16.8%) women with CIN2 biopsy exhibited higher-grade lesions on the surgical excision specimen or during follow-up. p16INK4a expression positively and negatively predicted the presence of higher-grade lesions in 17.19% and 86.67% patients, respectively. Ki-67 expression positively and negatively predicted the presence of higher-grade lesions in 40% and 88.24% patients, respectively.

Conclusions: Negative p16INK4a and Ki67 immunohistochemical staining can assure absence of a higher-grade lesion in more than 85% of patients with CIN2 biopsies and can be used to prevent overtreatment of these patients. Positive IHC staining for p16INK4a and Ki-67 did not predict CIN3 in patients with CIN2 biopsies.

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Conflict of interest statement

Conflicts of interest: None

Figures

Figure 1.
Figure 1.. Flowchart of sample selection and biomarker status.
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