Cervicovaginal cytokine profiles and their associations with colposcopic findings in adolescent girls and adult women in South Africa: an exploratory cross-sectional study

Colposcopy is used to evaluate cervical inflammation and detect precancerous and other cervical lesions; however, access remains limited in many low-resource settings. Identification of cervicovaginal immune biomarkers associated with specific colposcopic findings may provide insight into mucosal immune alterations linked to increased susceptibility to sexually transmitted infections (STIs) and human immunodeficiency virus (HIV), although these associations do not imply diagnostic or predictive utility in a cross-sectional context.

In this exploratory cross-sectional study, 203 adolescent girls (14–19 years) and adult women (25–35 years) from KwaZulu-Natal (KZN; n = 105) and the Western Cape (WC; n = 98) underwent colposcopic assessment for cervical ectopy, discharge, injury/inflammation, and leukoplakia. Cervicovaginal cytokines were quantified using multiplex Luminex assays. Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis (BV) were assessed. Logistic regression models identified correlates of colposcopic findings. Exploratory model performance metrics, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated to describe within-dataset model behaviour.

Overall, 75% of participants had at least one colposcopic finding. Leukoplakia was more prevalent in KZN (36% of adolescents and 22% of adults), while cervical discharge was most common in WC (36% in both age groups). In univariate analyses, injectable progestin use was associated with any colposcopic finding (OR = 2.10, p = 0.04), implant use was associated with ectopy in KZN (OR = 6.94, p = 0.04), and BV was associated with cervical discharge (OR = 3.37, p = 0.04). In the exploratory multivariable models, selected cervicovaginal cytokines showed finding- and site-specific associations with colposcopic outcomes. In KZN, higher granulocyte colony-stimulating factor (G-CSF) concentrations and parity were associated with cervical ectopy, while BV was associated with cervical discharge. In WC, interleukin-6 (IL-6) and macrophage inflammatory protein (MIP)-1β were associated with cervical ectopy, whereas lower MIP-1α concentrations were associated with leukoplakia. Measures of model performance varied across outcomes and sites, and should be interpreted within the context of the exploratory study design.

Cervicovaginal cytokine profiles were differentially associated with specific colposcopic findings in a site-specific manner. These findings are exploratory and hypothesis-generating, highlighting potential biological correlates of cervical changes. Further validation in larger longitudinal cohorts is required to determine whether these cross-sectional associations are reproducible and biologically meaningful.