The IL-23/IL-17 Axis in cutaneous verrucae: evidence from serum cytokine analysis in HPV infection

Cutaneous verrucae (warts) are benign epidermal proliferations caused by human papillomavirus (HPV) infection. The host immune response particularly T helper 17 (Th17) related cytokines such as interleukin-17A (IL-17A) and interleukin-23 (IL-23) plays a critical role in the regulation of viral control and inflammatory responses. However, the systemic levels of these cytokines in patients with verrucae have not been sufficiently characterized.

To investigate serum IL-17A and IL-23 levels in patients with cutaneous verrucae, to compare them with those of healthy controls, and to evaluate their associations with age, sex, number of lesions, disease duration, and lesion localization.

In this case-control study, 49 patients with palmoplantar or anogenital verrucae and 41 age- and sex-matched healthy controls were included. Serum IL-17A and IL-23 levels were measured using enzyme-linked immunosorbent assay (ELISA). Continuous variables were analyzed using the Mann-Whitney U test, and categorical variables using the chi-square test. Correlations between variables were assessed using Spearman correlation analysis.

The median serum IL-23 level was 11.8 pg/mL (interquartile range, IQR: 7.8-21.3) in patients with cutaneous verrucae and 8.8 pg/mL (IQR: 7.2-12.0) in controls, with a statistically significant difference (p = 0.018). The median serum IL-17A level was 16.6 pg/mL (IQR: 8.7-37.9) in patients and 16.4 pg/mL (IQR: 10.9-24.5) in controls, with no significant difference between the groups (p = 0.755). A strong positive correlation was observed between IL-17A and IL-23 levels in patients (rs = 0.880, p < 0.001). No significant associations were found between cytokine levels and age, sex, number of lesions, disease duration, or localization.

Elevated IL-23 levels and its strong positive correlation with IL-17A suggest that the IL-23/IL-17 Axis may play a role in immune activation associated with HPV-related cutaneous verrucae. IL-23 may represent a potential indicator of immune activation associated with cutaneous verrucae; however, its standalone diagnostic utility appears limited. Future studies with larger cohorts and tissue-level analyses are needed to further elucidate the role of Th17-related cytokines in the pathogenesis of verrucae.