Toll-like receptor expression across histological states of Epidermodysplasia Verruciformis

Abstract

Epidermodysplasia verruciformis (EV) is characterized by susceptibility to cutaneous {beta}-human papillomaviruses, persistent viral lesions and an increased risk of cutaneous squamous cell carcinoma (cSCC). We investigated whether expression of Toll-like receptors 3, 4, 5 and 9 (TLR3, TLR4, TLR5 and TLR9) differs across histological states within EV. Immunoreactivity was quantified by digital H-score using QuPath in 97 specimens from 28 patients, comprising 13 lesion-free skin samples, 15 flat warts and 69 cSCCs. Prespecified comparisons evaluated flat wart versus lesion-free skin, cSCC versus non-neoplastic tissue and invasive versus in situ cSCC, with invasive tumour differentiation assessed secondarily. Patient-clustered generalized estimating equations and false-discovery-rate (FDR) correction were used for inference. After correction for multiple testing, TLR9 H-scores were higher in flat warts than in lesion-free skin ({beta}=60.58; q=0.0332). Compared with non-neoplastic tissue, cSCC showed lower TLR3 ({beta}=-81.40; q=0.00745), higher TLR4 ({beta}=55.59; q=0.04793) and lower TLR9 expression ({beta}=-34.80; q=0.03412). TLR5 showed a nominal increase in cSCC that did not meet the FDR threshold. None of the four receptors differed significantly between invasive and in situ cSCC, and no differentiation trend remained significant after FDR correction. These findings show receptor-specific differences in TLR expression across histological states of EV, particularly involving TLR3, TLR4 and TLR9, although the diagnostic and prognostic significance of these tissue patterns remains to be established.

Predictive and Prognostic Value of Androgen Receptor Expression Across All Molecular Subtypes in Patients with Breast Cancer Who Received Neoadjuvant-Treatment: Single-Center Retrospective Analysis.
Harun Muğlu, Vedat Buğra Erol, Hakan Özçelik +14
Breast cancer (Dove Medical Press)22 Oct 2026Peer-reviewedCC BY-NCFull textOncologyEurope PMC
Immunophenotypic Features of T-Lymphocyte Distribution Across Histological and Molecular Subtypes of Serous Ovarian Neoplasms: A Retrospective Immunohistochemical Study
Grigory Demyashkin, Sofia Dorfman, Aleksandra Asaturova +11
Biomedicines1 Oct 2026Peer-reviewedCC BYFull textGeneral medicineEurope PMC
Intrafollicular PAI-1 Expression Is Associated with Absence of Histological Transformation During Long-Term Follow-Up in Follicular Lymphoma
Cecilie Dohrmann, Marie Hairing Enemark, Caroline Maren Stengaard Jensen +4
International Journal of Molecular Sciences1 Oct 2026Peer-reviewedCC BY 4.0Full textGeneral medicineCrossrefEurope PMC
Immunohistochemical Expression of Proliferating Cell Nuclear Antigen in Invasive Breast Carcinoma: Associations With Histological Grade and Ki-67 Expression.
Vikash Kumar, Amresh Kumar, Namita Singh +2
Cureus22 Sep 2026Peer-reviewedCC BYFull textOncologyEurope PMC
Clinicopathological Analysis of 1,000 Cases of Head and Neck Squamous Cell Carcinoma With Special Emphasis on Histological Variants and p16 Expression.
R P Sushma Kumari, M Mamatha, Naval Kishore Bajaj +1
Cureus7 Oct 2026Peer-reviewedCC BYFull textGeneral medicineEurope PMC

Cite

BibTeX RIS

BibTeX

@misc{junior2026tolllike,
  title = {{Toll-like receptor expression across histological states of Epidermodysplasia Verruciformis}},
  author = {L. A. R. Froes Junior and C. C. d. A. Pereira and L. L. d. C. Silva and M. G. Saldanha and N. V. Pereira and W. R. Pereira de Oliveira and M. N. Sotto},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.29.755296},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755296v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Toll-like receptor expression across histological states of Epidermodysplasia Verruciformis
AU  - L. A. R. Froes Junior
AU  - C. C. d. A. Pereira
AU  - L. L. d. C. Silva
AU  - M. G. Saldanha
AU  - N. V. Pereira
AU  - W. R. Pereira de Oliveira
AU  - M. N. Sotto
PY  - 2026
DA  - 2026/09/29
PB  - bioRxiv
DO  - 10.64898/2026.09.29.755296
UR  - https://www.biorxiv.org/content/10.64898/2026.09.29.755296v1
AB  - Epidermodysplasia verruciformis (EV) is characterized by susceptibility to cutaneous {beta}-human papillomaviruses, persistent viral lesions and an increased risk of cutaneous squamous cell carcinoma (cSCC). We investigated whether expression of Toll-like receptors 3, 4, 5 and 9 (TLR3, TLR4, TLR5 and TLR9) differs across histological states within EV. Immunoreactivity was quantified by digital H-score using QuPath in 97 specimens from 28 patients, comprising 13 lesion-free skin samples, 15 flat warts and 69 cSCCs. Prespecified comparisons evaluated flat wart versus lesion-free skin, cSCC versus non-neoplastic tissue and invasive versus in situ cSCC, with invasive tumour differentiation assessed secondarily. Patient-clustered generalized estimating equations and false-discovery-rate (FDR) correction were used for inference. After correction for multiple testing, TLR9 H-scores were higher in flat warts than in lesion-free skin ({beta}=60.58; q=0.0332). Compared with non-neoplastic tissue, cSCC showed lower TLR3 ({beta}=-81.40; q=0.00745), higher TLR4 ({beta}=55.59; q=0.04793) and lower TLR9 expression ({beta}=-34.80; q=0.03412). TLR5 showed a nominal increase in cSCC that did not meet the FDR threshold. None of the four receptors differed significantly between invasive and in situ cSCC, and no differentiation trend remained significant after FDR correction. These findings show receptor-specific differences in TLR expression across histological states of EV, particularly involving TLR3, TLR4 and TLR9, although the diagnostic and prognostic significance of these tissue patterns remains to be established.
ER  -

Abstract

Related

Cite