# Conservative management of cervical intraepithelial neoplasia grade 2 and immunohistochemical staining of p16 and Ki-67: Data from a Brazilian institution

**Authors:** Amanda Leal Ferreira, Yara Lúcia Mendes Furtado de Melo, Elyzabeth Avvad Portari, Dione Corrêa Araújo Dock, Nilma Valéria Ferreira Caldeira, Saint Clair dos Santos Gomes Júnior, Fabio Bastos Russomano, Cecília Vianna de Andrade

PMC · DOI: 10.1371/journal.pone.0342001 · PLOS One · 2026-02-25

## TL;DR

This study examines how often cervical lesions called CIN2 regress without treatment and whether biomarkers like p16 and Ki-67 can predict this outcome.

## Contribution

The study provides data on CIN2 regression rates and evaluates the predictive value of p16 and Ki-67 biomarkers in a Brazilian cohort.

## Key findings

- CIN2 regression occurred in 76% of cases within approximately 12 months.
- Baseline characteristics, including p16 and Ki-67, were not statistically associated with lesion regression.
- The median time to regression was 357 days with a confidence interval of 236.6–477.4 days.

## Abstract

Cervical intraepithelial neoplasia grade 2 (CIN2) includes both transient HPV infections and precursor lesions of cervical cancer. Conservative management aims to avoid overtreatment, especially in reproductive-aged women.

To describe the clinical outcomes and time to lesion regression among conservatively managed, biopsy-confirmed CIN2 cases, and to explore whether baseline characteristics, including p16 and Ki-67, were associated with lesion regression.

An observational cohort study was conducted in patients with CIN2, as determined by cervical biopsy. Participants were followed up with cytology and colposcopy every 6 months, and outcomes were categorized as regression or no regression. At least two pathologists evaluated p16 immunohistochemical staining according to LAST criteria. Ki-67 staining was considered positive when at least 50% of cells in the lesion were stained, as determined by digital quantification. Bivariate analysis and survival curve analyses were conducted, with significant associations defined as p-values <0.05.

Fifty patients with a mean age of 30.5 years were included in the study; 76% (38/50) showed regression. The median time to regression was 357 days (SE = 61.4 days; 95% CI: 236.6–477.4 days). The baseline characteristics, including p16 and Ki-67, were not statistically associated with regression, likely due to the small sample size.

CIN2 regression occurred in 76% of cases, with median times of approximately 12 months for regression and 32 months for progression. No statistically significant associations were detected between baseline characteristics, including biomarkers, and lesion regression in this exploratory study.

## Linked entities

- **Proteins:** CDKN2A (cyclin dependent kinase inhibitor 2A), Mki67 (antigen identified by monoclonal antibody Ki 67)
- **Diseases:** cervical cancer (MONDO:0002974)

## Full-text entities

- **Genes:** CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}
- **Diseases:** atypical squamous cells (MESH:D065309), invasive carcinoma (MESH:D009361), precancerous (MESH:D011230), immunodeficiency (MESH:D007153), preterm birth (MESH:D047928), HPV infections (MESH:D030361), cervical disease (MESH:D002575), inflammatory (MESH:D007249), ASC-H (MESH:D000081483), Cervical cancer (MESH:D002583), cancer (MESH:D009369), CIN 1 (MESH:D002578), obstetric (MESH:D048949)
- **Chemicals:** formalin (MESH:D005557), estrong (-), paraffin (MESH:D010232)
- **Species:** Human immunodeficiency virus (species) [taxon 12721], Homo sapiens (human, species) [taxon 9606], Human immunodeficiency virus 1 (no rank) [taxon 11676], Mus musculus (house mouse, species) [taxon 10090]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12935196/full.md

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12935196/full.md

## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC12935196/full.md

---
Source: https://tomesphere.com/paper/PMC12935196