An Improved Protocol for Comprehensive Etiological Characterization of Skin Warts and Determining Causative Human Papillomavirus Types in 128 Histologically Confirmed Common Warts

Abstract

Human papillomaviruses (HPVs) are etiologically associated with various benign and malignant neoplasms of cutaneous and mucosal epithelia. We describe an improved diagnostic protocol for comprehensive characterization of causative HPV types in common warts, in which broad-spectrum PCRs followed by Sanger sequencing, two previously described and seven newly developed type-specific quantitative real-time PCRs (qPCRs) coupled with the human beta-globin qPCR were used for: (i) diagnosis of HPV infection in warts; (ii) estimation of cellular viral loads of all HPV types detected; and (iii) determination of their etiological role in 128 histologically confirmed fresh-frozen common wart tissue samples. A total of 12 different causative HPV types were determined in 122/126 (96.8%) HPV-positive warts, with HPV27 being most prevalent (27.0%), followed by HPV57 (26.2%), HPV4 (15.1%), HPV2 (13.5%), and HPV65 (7.9%). The cellular viral loads of HPV4 and HPV65 were estimated for the first time in common warts and were significantly higher than the viral loads of HPV2, HPV27, and HPV57. In addition, we showed for the first time that HPV65 is etiologically associated with the development of common warts in significantly older patients than HPV27 and HPV57, whereas HPV4-induced warts were significantly smaller than warts caused by HPV2, HPV27, HPV57, and HPV65.

Characterization of type-specific HPV prevalence in a population of persistent cutaneous warts in Flanders, Belgium

“…To the best of our knowledge, the most comprehensive study exploring HPV genotyping and including a viral load component was the study conducted by Skubic et al 46 . In contrast, the latter study focused on histological specimens, hereby generating strong evidence on genotype distribution and investigating the role of HPV viral load in cutaneous warts 46 .…”

“…To the best of our knowledge, the most comprehensive study exploring HPV genotyping and including a viral load component was the study conducted by Skubic et al 46 . In contrast, the latter study focused on histological specimens, hereby generating strong evidence on genotype distribution and investigating the role of HPV viral load in cutaneous warts 46 . Our findings, obtained by the collection of cutaneous swabs, largely confirm the findings by Skubic et al, showing the highest prevalence of HPV 27 and 57, with comparable levels of viral load distribution as well, despite essentially different starting material.…”

“…Number of warts being a risk factor for persistence is to be expected, knowing that persistent warts are resistant to treatment and, by definition, have a duration longer than 6 months, which increases the risk of autoinoculation and transmission of the HPV infection from one body site to another. As regards to the role of HPV genotyping, seeing that the high viral load of HPV 27 and 57 results in a subsequent high infectious potential, these types appear to be omnipresent in the population, not only in persistent warts but also in warts that are defined as not persistent 3 , 27 , 46 . This finding makes them an inadequate predictor of risk.…”

Viral Diseases in Dermatology

“…In this context, the editors of the journal Viruses decided to create a Special Issue, entitled “Viral Diseases in Dermatology”. It encompasses six articles that cover various aspects of viral skin diseases [ 1 , 2 , 3 , 4 , 5 , 6 ].…”

“…This Special Issue sheds light on various aspects of viral diseases in dermatology, including, but not limited to, pathophysiology and treatment. To be brief, the key published articles in this Special Issue addressed the following topics: skin herpes viruses and their manifestations as well as management [ 1 , 2 ]; viral triggers for endemic pemphigus foliaceus [ 3 ]; and the etiological characterization of skin warts [ 4 ]. Additionally, the mechanisms and management of skin lesions in COVID-19 were highlighted in two articles [ 5 , 6 ].…”