Cervical Cytokine Profile in High‐Grade Squamous Intraepithelial Lesions
Talles Henrique de Araújo Pontes, Amaxsell Thiago Barros de Souza, Carolina de O. Mendes‐Aguiar, Maria do Perpétuo Socorro Nobre Medeiros e Silva, Juliana Dantas de Araújo Santos Camargo, George Alexandre Lira, Ricardo Ney Cobucci, Deyse de Souza Dantas, Janaina Cristiana de Oliveira CrispimABSTRACT
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.