Cervical Cytokine Profile in High-Grade Squamous Intraepithelial Lesions
Talles Henrique de Araújo Pontes1, Amaxsell Thiago Barros de Souza1, Carolina de O Mendes-Aguiar1,2
1Postgraduate Program in Science Applied to Women's Health, Federal University of Rio Grande Do Norte, Natal, Brazil.
Objectives:
This study aimed to characterise the local cytokine milieu in the cervicovaginal environment of women with HSIL compared with healthy controls.
Methods:
In this case-control study, cervical samples were collected from 84 women aged 20-49 years, including 57 patients with histologically confirmed HSIL and 27 healthy controls. Levels of IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ and IL-17A were quantified in cervicovaginal lavage fluid using a Cytometric Bead Array. Cytokine ratios were calculated to assess the balance between pro-inflammatory and regulatory immune responses. Statistical comparisons between groups were performed using the Mann-Whitney test.
Results:
Women with HSIL exhibited significantly lower concentrations of TNF (p = 0.030) and IL-2 (p = 0.010) compared with controls. Correspondingly, the TNF/IL-10 (p = 0.018) and TNF/IL-4 (p = 0.032) ratios were markedly decreased, suggesting impaired Th1-mediated immune activation. No significant differences were observed for IL-17A levels or IL-17A/IL-6 ratios, suggesting that Th17-associated soluble mediators may not be the predominant drivers of the observed immunomodulation in this context, although broader Th17 involvement cannot be excluded.
Conclusions:
HSIL is characterised by reduced TNF and IL-2 expression and a suppressed TNF/IL-10 and TNF/IL-4 balance, revealing a shift towards an immunoregulatory profile independent of Th17 activity. This cytokine signature suggests an immune milieu favouring lesion persistence and provides a potential framework for developing cytokine-based biomarkers and immunotherapeutic strategies in HPV-associated cervical disease.
