# NGAL and HPV Subtypes in Cervical Carcinoma: Implications for Cancer Progression and Treatment Response

**Authors:** Behar Raci, Snezana Stojkovska, Gezim Hodolli, Violeta Klisarovska, Goran Dimitrov, Shemsi Veseli, Arta Kameri-Jusufi, Mentor Kurshumliu, Diellor Rizaj, Arben Sinani

PMC · DOI: 10.3390/cimb48020234 · Current Issues in Molecular Biology · 2026-02-23

## TL;DR

This study explores the role of NGAL as a potential biomarker in cervical cancer, finding it may reflect tumor inflammation rather than HPV subtype, with possible implications for prognosis.

## Contribution

The study evaluates NGAL levels in cervical cancer patients in relation to HPV subtypes and treatment response, revealing its potential as a tumor-associated inflammation marker.

## Key findings

- NGAL levels increased in inoperable patients and advanced FIGO stages, suggesting potential prognostic value.
- No significant association was found between NGAL levels and HPV subtypes.
- HPV 16 was the most common subtype, and midlife women showed the highest HPV positivity rate.

## Abstract

Background/Objectives: Cervical cancer is a prominent source of morbidity and mortality among women, particularly in low- and middle-income nations. Neutrophil Gelatinase-Associated Lipocalin (NGAL), a glycoprotein involved in cancer-related activities, has been proposed as a biomarker; however, its involvement in cervical cancer remains unknown. The study aim is to evaluate the prognostic significance of serum NGAL levels in cervical cancer patients in relation to International Federation of Gynecology and Obstetrics (FIGO) stage, operability, and HPV subtype distribution before and after treatment. Methods: The study involved 130 women, 100 with histologically proven cervical cancer and 30 healthy controls. The serum NGAL levels were determined before and after treatment using an ELISA test. HPV genotyping was carried out using real-time PCR on 21 high- and low-risk subtypes. Results: NGAL levels increased marginally during therapy (from 134 to 144 ng/mL; p = 0.28), but the rise was significant in inoperable patients (p = 0.02) and increased with advanced FIGO stage, although this did not reach statistical significance (p = 0.07). HPV 16 was the most common subtype (26.0%), while women aged 51–60 had the highest overall HPV positive rate (72.7%). There was no significant association between NGAL levels and HPV subtypes (p = 0.17). Conclusion: NGAL does not appear to be an accurate short-term indicator of therapy response. However, increased levels in advanced-stage and inoperable instances indicate prognostic significance. NGAL most likely represents tumor-associated inflammation rather than HPV subtype. These findings support its possible inclusion in future biomarker panels, subject to validation in bigger investigations. Persistent HPV infection in midlife women highlights the significance of ongoing screening.

## Linked entities

- **Proteins:** LCN2 (lipocalin 2)
- **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}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, MCM2 (minichromosome maintenance complex component 2) [NCBI Gene 4171] {aka BM28, CCNL1, CDCL1, D3S3194, DFNA70, MITOTIN}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, MCM7 (minichromosome maintenance complex component 7) [NCBI Gene 4176] {aka CDC47, MCM2, P1.1-MCM3, P1CDC47, P85MCM, PNAS146}
- **Diseases:** autoimmune disorders (MESH:D001327), carcinogenesis (MESH:D063646), Noncommunicable Diseases (MESH:D000073296), acute kidney injury (MESH:D058186), fatigue (MESH:D005221), reproductive organ malignancies (MESH:D060737), HPV infection (MESH:D030361), cervical malignancies (MESH:D002575), hypoxia (MESH:D000860), planocellular carcinoma (MESH:D002294), IIIC (MESH:C566891), hyperlipidemia (MESH:D006949), inflammation (MESH:D007249), genital warts (MESH:D003218), hepatic impairment (MESH:D008107), injury to (MESH:D014947), dysplasia (MESH:D015792), HSIL (MESH:D000081483), Cervical Carcinoma (MESH:D002583), Tumor (MESH:D009369), adenocarcinoma cervicis uteri (MESH:D000230), diabetes (MESH:D003920), adenocarcinoma of the cervix uteri (MESH:D002578), renal dysfunction (MESH:D007674), FIGO (MESH:D005831), breast, pancreatic, and colorectal cancer (MESH:D001943), aggressiveness (MESH:D010554), necrosis (MESH:D009336), invasive (MESH:D009361), tissue injury (MESH:D017695), metastases (MESH:D009362), breast, colorectal, pancreatic, and endometrial cancers (MESH:C537262), viral infections (MESH:D014777), carcinogenic (MESH:D011230), death (MESH:D003643), hypertension (MESH:D006973), tumorigenic (MESH:D002471), -infection (MESH:D007239), nodal (MESH:D013611)
- **Chemicals:** iron (MESH:D007501), TMB (MESH:C021758), bilirubin (MESH:D001663), creatinine (MESH:D003404), cisplatin (MESH:D002945), PAP (-), urea (MESH:D014508)
- **Species:** Human papillomavirus (species) [taxon 10566], Human papillomavirus 16 (serotype) [taxon 333760], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** Q31A

## Full text

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## Figures

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## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12939286/full.md

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Source: https://tomesphere.com/paper/PMC12939286