Evidence map›Paper›PMID 40507244›Full record

ArticleCancers2025

Protein Biomarkers Enable Sensitive and Specific Cervical Intraepithelial Neoplasia (CIN) II/III+ Detection: One Step Closer to Universal Cervical Cancer Screening.

Samrin F Habbani, Sayeh Dowlatshahi, Nathanael Lichti, Meaghan Broman, Lucy Tecle, Scott Bolton, Lisa Flowers, Rafael Guerrero-Preston, Jacqueline C Linnes, Sulma I Mohammed

Abstract read
In one paragraph

Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Samrin F HabbaniDepartment of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.ORCID 0000-0002-4359-1301
Sayeh DowlatshahiWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.ORCID 0000-0001-8011-9471
Nathanael LichtiBindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA.ORCID 0000-0003-2487-0708
Meaghan BromanDepartment of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.ORCID 0000-0001-5473-1616
Lucy TecleWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Scott BoltonWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Lisa FlowersDepartment of Obstetrics and Gynecology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Rafael Guerrero-PrestonLifeGene Biomarks, Toa Baja 00949, Puerto Rico.
Jacqueline C LinnesWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.ORCID 0000-0003-4962-0908
Sulma I MohammedDepartment of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.

Funding

Precision methylation biomarkers for cervical cancer prevention in low resource settings in Latin AmericaR44CA254690 · NCI · LIFEGENE-BIOMARKS, INC. · PI GUERRERO-PRESTON, RAFAEL · 2021 to 2023
$2.4M
Precision screening in self-collected samples to reduce cervical cancer disparities among LatinasR42MD018231 · NIMHD · LIFEGENE-BIOMARKS, INC. · PI Rafael Guerrero-Preston · 2024 to 2026
$2.1M
Point-of-care screening test for early cervical cancer detectionR01CA246315 · NCI · PURDUE UNIVERSITY · PI LINNES, JACQUELINE, MOHAMMED, SULMA IBRAHIM · 2020 to 2024
$2.0M
Precision methylation biomarkers linked to cancer disparitiesR44MD014911 · NIMHD · LIFEGENE-BIOMARKS, INC. · PI GUERRERO-PRESTON, RAFAEL · 2019 to 2021
$1.7M
NCI NIH HHS R01 CA246315NCI NIH HHS R44 CA254690NIH HHS R01CA246315NIMHD NIH HHS R42 MD018231NIMHD NIH HHS R44 MD014911
6 · The paper itself

Abstract

BACKGROUND/

objectivesCervical cancer (CC) is a significant global health challenge, particularly in low- and middle-income countries (LMICs), where limited access to human papillomavirus (HPV) vaccination and effective CC screening results in a majority of cases and fatalities among women. Moreover, existing vaccines do not target HPV-independent cancers. Current screening methods are expensive and time-consuming, with a limited emphasis on CC protein biomarkers. Therefore, we aimed to validate critical markers that allow the development of affordable point-of-care screening tests for resource-limited settings.

methodsThis study first optimized a cell lysis and protein extraction protocol for CC cell lines and clinical cervical swabs. Subsequently, four proteins-topoisomerase II alpha (TOP2A), minichromosome maintenance complex component 2 (MCM2), valosin-containing protein (VCP), and cyclin-dependent kinase inhibitor 2A (p16INK4a)-were quantified in the resulting lysates using enzyme-linked immunosorbent assays, as well as in cervical tumors and squamous intraepithelial lesions (SILs) using immunohistochemistry for further validation.

resultsAcetone precipitation allowed for efficient cell isolation, and radioimmunoprecipitation assay buffer yielded the highest protein recovery. VCP and p16INK4a were overexpressed across all cancer cell lines compared to primary cells. All four biomarkers were overexpressed in high-grade SIL (HSIL) swab specimens and tumor samples, including CC subtypes, G1-G3 tumor grades, and HSILs. Lastly, we showed that the proteins could accurately classify swabs and tissue specimens into clinically relevant groups.

conclusionsThe quantitative analysis of these biomarkers, along with the subsequent sensitive and specific clinical classification, highlights their potential application in SIL early detection and CC prevention, particularly in LMICs.

Indexed as

cervical cancercervical intraepithelial neoplasiacervical precancerous lesionsearly detectionhigh-grade squamous intraepithelial lesionslow- and middle-income countriesprotein biomarkers

Identifiers

PMID40507244
PMCPMC12153835

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.