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

Autores

Palavras-chave:

Uterine cervical dysplasia, Cyclin-dependent kinase inhibitor p21, Ki-67 antigen, Cervical intraepithelial neoplasia, Cervical intraepithelial neoplasia grade 2, CIN2, p16INK4a, Ki-67

Resumo

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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Biografia do Autor

Amanda Leal Ferreira, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

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.

Nasle Domingues Dibe, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

MD. Gynecologist, 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.

Bruna Rodrigues de Paiva, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

MD. Postgraduate Student in Nutrology, 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.

Elyzabeth Avvad Portari, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

MD, MSc, PhD. Pathologist, Researcher in 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.

Dione Corrêa de Araújo Dock, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

MD. Physician and Pathologist, 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.

Nilma Valéria Caldeira Ferreira, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

BSc. Immunohistochemistry Technician, 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.

Saint Clair Gomes Junior, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

MD, MSc, PhD. Gynecologist, Center for the Clinical and Surgical Care of Women, 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, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

MD, MSc, PhD. Gynecologist, Center for the Clinical and Surgical Care of Women, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro (RJ), Brazil.

Cecília Vianna de Andrade, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

MD, MSc, PhD. Pathologist, 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.

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Publicado

2025-03-24

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1.
Ferreira AL, Dibe ND, Paiva BR de, Portari EA, Dock DC de A, Ferreira NVC, Gomes Junior SC, Russomano FB, Andrade CV de. Cervical Intraepithelial Neoplasia grade 2 biopsy: Do p16INK4a and Ki-67 biomarkers contribute to the decision to treat? A cross-sectional study. Sao Paulo Med J [Internet]. 24º de março de 2025 [citado 15º de outubro de 2025];142(1):1-9. Disponível em: https://periodicosapm.emnuvens.com.br/spmj/article/view/2990

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