• Amanda Leal Ferreira, Nasle Domingues Dibe, Bruna Rodrigues de Paiva, Elyzabeth Avvad Portari, Dione Corrêa de Araújo Dock, Nilma Valéria Caldeira Ferreira, Gomes JuniorSaint ClairSC0000-0002-1554-943XBSc, PhD. Researcher in Clinical Research Unit, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro (RJ), Brazil., Fábio Bastos Russomano, and Cecília Vianna de Andrade.
• MSc. Biomedical and PhD Student, Laboratory of Diagnosis Pathology and Cytopathology, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro (RJ), Brazil.
• Sao Paulo Med J. 2023 Jan 1; 142 (1): e2022527e2022527.

BackgroundManaging 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.ObjectivesTo 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 SettingCross-sectional study conducted at a referral center for treating uterine cervical lesions.MethodsIn 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.ResultsThirteen (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.ConclusionsNegative 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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