Toll-like receptor patterns in epidermodysplasia verruciformis associated - squamous cell carcinomas

Epidermodysplasia verruciformis (EV) is a rare genetic condition characterized by viral warts and an increased risk of squamous cell carcinoma (SCC), particularly associated with specific human papillomavirus (HPV) types, notably beta-HPV variants 5 and 8. Toll-like receptors (TLRs) are crucial for immune response regulation and may contribute to cancer development in EV. This study aimed to assess the expression levels of TLRs 3, 4, 5, and 9 in SCC samples from EV patients versus those without EV (NEV) to understand their potential roles in EV-related carcinogenesis. We examined tumour samples from 18 patients with EV alongside samples from 90 NEV participants. Techniques included tissue microarray analysis and conventional histological evaluation, with immunohistochemistry performed to detect TLR expression. Controls were included to validate the specificity of the results, and statistical analyses employed the Kruskal-Wallis test with Dunn-Bonferroni post-hoc comparisons. TLRs 3, 4, 5, and 9 were detected in both patient groups, with distinct expression patterns. TLR3 levels were higher in the normal skin of EV patients, while TLR9 was more prominent in tumours. In NEV patients, TLR3 and TLR4 expression varied with tumour stages; invasive SCC showed increased TLR5 and TLR9 levels. EV samples showed significantly higher TLR4 and TLR9 expression relative to NEV samples. The differing TLR expression patterns indicate diverse immune mechanisms involved in EV-related carcinogenesis, suggesting that TLRs could be potential therapeutic targets, meriting further investigation into their roles in tumour growth regulation.