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Background The quantification of human papilloma virus (HPV)‐induced skin lesions is essential for the clinical assessment of the course of disease and the response to treatment. However, clinical assessments that measure dimensions of lesions using a caliper do not provide complete insight into three‐dimensional (3D) lesions, and its inter‐rater variability is often poor. Objective The aim of this study was to validate a stereophotogrammetric 3D camera system for the quantification of HPV‐induced lesions. Methods The camera system was validated for accuracy, precision and interoperator and inter‐rater variability. Subsequently, 3D photographs were quantified and compared to caliper measurements for clinical validation by Bland–Altman modelling, based on data from 80 patients with cutaneous warts (CW), 24 with anogenital warts (AGW) patients and 12 with high‐grade squamous intraepithelial lesions of the vulva (vulvar HSIL) with a total lesion count of 220 CW, 74 AGW and 31 vulvar HSIL. Results Technical validation showed excellent accuracy [coefficients of variation (CV) ≤ 0.68%] and reproducibility (CVs ≤ 2%), a good to excellent agreement between operators (CVs ≤ 8.7%) and a good to excellent agreement between different raters for all three lesion types (ICCs ≥ 0.86). When comparing 3D with caliper measurements, excellent biases were found for diameter of AGW (long diameter 5%), good biases were found for diameter of AGW (short diameter 10%) and height of CW (8%), and acceptable biases were found for the diameter of CW (11%) and vulvar HSIL (short diameter 14%, long diameter 16%). An unfavourable difference between these methods (bias 25%) was found for the assessment of height of AGWs. Conclusion Stereophotogrammetric 3D imaging is an accurate and reliable method for the clinical visualization and quantification of HPV‐induced skin lesions., Linked Commentary: M. Skerlev et al. J Eur Acad Dermatol Venereol 2019; 33: 1445–1446. https://doi.org/10.1111/jdv.15791.

Summary Background Topical ionic contraviral therapy (ICVT) with digoxin and furosemide inhibits the potassium influx on which DNA viruses rely for replication. Therefore, ICVT was hypothesized to be a potential novel treatment for cutaneous warts. Objectives To assess the clinical efficacy, safety and tolerability of ICVT in adults with cutaneous warts. The secondary objective was to gain insight into the underlying working mechanism of ICVT. Methods Treatment with ICVT was assessed for efficacy, safety and tolerability in a single‐ centre, randomized, double‐blind, placebo‐controlled phase IIA trial. Eighty adult patients with at least two cutaneous warts (plantar or common) were randomized to one of four treatments: digoxin + furosemide (0·125%), digoxin (0·125%), furosemide (0·125%) or placebo. The gel was administered once daily for 42 consecutive days. Predefined statistical analysis was performed with a mixed‐model ancova. The trial was registered at ClinicalTrials.gov with number NCT02333643. Results Wart size and human papillomavirus (HPV) load reduction was achieved in all active treatment groups. A statistically significant reduction in wart diameter of all treated warts was shown in the digoxin + furosemide treatment group vs. placebo (−3·0 mm, 95% confidence interval −4·9 to −1·1, P = 0·002). There was a statistically significant reduction in the HPV load of all treated warts in the digoxin + furosemide group vs. placebo (−94%, 95% confidence interval −100 to −19, P = 0·03). With wart size reduction, histologically and immunohistochemically defined viral characteristics disappeared from partial and total responding warts. Conclusions This study demonstrates the proof of concept for the efficacy of topical ICVT in adults with cutaneous warts., What's already known about this topic? Cutaneous warts are caused by the human papillomavirus (HPV).Ionic contraviral therapy (ICVT) might be a potential treatment for cutaneous warts.A previous phase I/II open‐label study demonstrated the safety and efficacy of ICVT. What does this study add? Proof of concept for the efficacy of topical ICVT in adults with cutaneous warts.Topical ICVT demonstrates a favourable safety profile, with the effects most pronounced when it is combined in a formulation for common warts.Wart size reduction was related to HPV load reduction measured by quantitative polymerase chain reaction (qPCR) in swabs.qPCR is a valuable disease biomarker for drug development in cutaneous warts. https://doi.org/10.1111/bjd.17803 available online https://www.bjdonline.com/article/

Background The clinical appearance of cutaneous warts is highly variable and not standardised. Objectives The aim of this study was to develop and validate a reproducible clinical tool for the standardised assessment of cutaneous warts to distinguish these lesions accurately. Methods Nine morphological characteristics were defined and validated regarding intra- and inter-observer agreement. Based on literature and semi-structured interviews, a systematic dichotomous assessment tool, the Cutaneous WARTS diagnostic tool (CWARTS diagnostic tool) was developed. The validation consisted of two independent parts performed with photographs from the recent WARTS-2 trial. In part A, the CWARTS diagnostic tool was tested by 28 experienced physicians who assessed photographs of 10 different warts to investigate inter-observer concordance. In part B, morphological characteristics were validated by blinded and independent scoring of 299 photographs by 6 different observers. Part B also entailed re-assessment of the photographs after at least 1 week. Primary outcome measurement was the intraclass correlation coefficient (ICC). Results Presence of black dots (capillary thrombosis) had the greatest ICC (0.85) for inter-observer agreement in part A, followed by arrangement (0.65), presence of border erythema(0.64) and sharpness of the border (0.60). In part B results were similar for inter-observer agreement with presence of black dots having the highest ICC (0.68), followed by border erythema (0.64), arrangement (0.58) and colour (0.55). For intra-observer agreement, presence of black dots had the highest agreement (0.69), followed by presence of border erythema (0.64) and colour (0.55). Conclusions The wart phenotype can be reliably assessed by the CWARTS diagnostic tool. This article is protected by copyright. All rights reserved.

BACKGROUND: Cutaneous warts have a cure rate after therapy of no more than approximately 50%. Recently, we developed and validated a standard assessment tool for warts (Cutaneous WARTS diagnostic tool, CWARTS) based on phenotypical characteristics.OBJECTIVES: To assess whether patient and morphological wart characteristics predict the human papillomavirus (HPV) type in a specific wart and whether these characteristics as well as the HPV type predict a favourable treatment response.METHODS: Photographs were used to score nine morphological wart characteristics using the newly developed CWARTS tool. Genotyping of 23 wart-associated HPV types was performed using the hyperkeratotic skin lesion-polymerase chain reaction/multiplex genotyping assay. The results were correlated with a favourable response to treatment with monochloroacetic acid, cryotherapy or a combination of cryotherapy and salicylic acid. Odds ratios were calculated using logistic regression in a generalized estimating equations model.RESULTS: Black dots (capillary thrombosis) strongly predicted the presence of any HPV type in a wart. From all characteristics tested, the HPV type most strongly predicted the treatment response when the warts were treated with monochloroacetic acid or a combination of cryotherapy and salicylic acid with a significantly decreased treatment response if the warts contained HPVs of the alpha genus (HPV2, HPV27 or HPV57). When cryotherapy alone was used for common warts, HPV type did not play a role, but cryotherapy was less effective in the presence of callus and when the wart was located deeper in the skin.CONCLUSIONS: Morphological characteristics of the warts and the HPV genotype influence treatment outcome and thus potentially influence future treatment decisions for common and plantar warts