Human papillomavirus type 94-associated flat warts and review of reported cases.

To date, 10 types of human papillomavirus have been identified that cause flat warts, including human papillomavirus type 3, which belongs to species group 2 of the genus alpha papillomavirus. Among these 10 types, human papillomavirus type 94 is most closely related to human papillomavirus type 10, sharing 86% homology. In this study, we conducted polymerase chain reaction analysis with sequencing on samples obtained from cutaneous lesions located on the face and lower legs of an individual, revealing the presence of human papillomavirus type 94. Dermatoscopic findings revealed numerous dotted vessels within one group of macular brown lesions located on the lower leg, which contributed to the diagnosis of flat warts. An online search revealed that human papillomavirus type 94 has previously been detected in various skin diseases, and we provide a review of prior reports.

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

Cutaneous warts are benign skin lesions caused by the human papillomavirus (HPV). Even though they are considered benign, they can have a considerable impact on the quality of life and cause serious illness in certain immunocompromised populations. Studies have shown that the efficacy of wart treatment is dependent on the causative HPV type. Therefore, in this article, we aim to determine the HPV genotype-specific prevalence in cutaneous warts of a Flemish population as part of the Omnivirol-Salycilic acid randomized controlled trial. Swab samples of cutaneous warts (n = 269) were collected during enrollment. The DNA extraction was performed on the automated NucliSENS® easyMAG® system (bioMérieux). The samples were analyzed with two separate in-house PCR assays capable of detecting the most prevalent cutaneous HPV types (i.e. wart-associated HPV qPCR) as well as the most relevant mucosal types (i.e. RIATOL qPCR assay). In total, the type-specific prevalence of 30 distinct HPV genotypes was determined. The beta-globin gene was used as a cellularity control and for viral load quantification. Data concerning wart persistence, previous treatment, wart type, and other relevant wart and patient characteristics was collected through a baseline questionnaire. The study population consisted mostly of persistent warts considering that 98% (n = 263) of the sampled skin lesions were older than six months and 92% (n = 247) had undergone previous treatment. The most prominent wart type was the mosaic verruca plantaris (42%, n = 113). The most prevalent HPV types were cutaneous HPV types 27 (73%, n = 195), 57 (63%, n = 169), and 2 (42%, n = 113). Only 2% (n = 6) of the lesions was HPV negative. The highest median viral loads were observed with HPV27 and 57 (i.e. 6.29E+04 and 7.47E+01 viral copies per cell respectively). The multivariate analysis found significant associations between wart persistence and certain wart types, the number of warts, and HPV genotypes. Based on these findings, persistent warts are more likely to: (1) be verruca vulgaris, verruca plantaris simple or mosaic, (2) to manifest as multiple warts, (3) and to be negative for HPV type 2 or 4. These characteristics can be useful in the clinical setting for future risk stratification when considering treatment triage and management. Trial registration: NCT05862441, 17/05/2023 (retrospectively registered).

Evaluation of combined treatment with Er:YAG laser and long-pulsed Nd:YAG laser for the treatment of recalcitrant warts: A prospective randomized controlled trial.

BACKGROUND: Viral warts are common infectious skin disease induced by human papillomavirus (HPV). Lasers have been used for warts treatment in recent years with variable success rates. OBJECTIVE: This study aimed to prospectively evaluate combined treatment with Er:YAG laser and long-pulsed Nd:YAG laser compared to Er:YAG laser for the treatment of recalcitrant warts after one session. MATERIALS AND METHODS: This study included 240 lesions from 24 patients. All the lesions were diagnosed clinically as recalcitrant warts after failure of topical treatment and cryotherapy. About 120 lesions underwent a combined therapy of Er:YAG and long-pulsed (LP) Nd:YAG lasers, and the remaining 120 lesions underwent Er:YAG laser therapy only. The clearance rate was evaluated 5 weeks after and classified by three-graded evaluation: complete response, partial response and poor response. RESULTS: The clearance rate in the combined Er:YAG + LP Nd:YAG lasers group was, statistically significant, higher than that of the Er:YAG laser group (p = 0.008). The complete response rate was 48% (58 of 120 warts) for the Er:YAG +LP Nd:YAG lasers group and only 29% (35 of 120 warts) for the Er:YAG laser group. CONCLUSION: The combination of Er:YAG and long-pulsed Nd:YAG lasers is more effective than Er:YAG laser alone in treating recalcitrant warts after single session.

A Clinico-Pathological Study of Vulvo-Vaginal Disease at a Nigerian Tertiary Health Facility.

INTRODUCTION: The vulva and vagina are of great significance to womanhood owing to the myriads of specialized functions they perform. The diseases of this organ have physical, social, mental, and psychological ramifications. The aim of this work is to study the pathological pattern and clinical presentation of diseases of the vulva and vagina at the Department of Anatomical Pathology and Forensic Medicine of the Jos University Teaching Hospital between 1st January 2011 and December 31st, 2020. METHODOLOGY: This study is descriptive of all cases of histologically diagnosed vulval and vaginal lesions seen at the Center. Histological diagnosis, biodata, and clinical information of patients were retrieved from the medical records. Data realized were analyzed and presented in tables as simple frequencies, percentages, ranges, and measures of central tendencies. RESULTS: Two hundred and fifteen vulval and vaginal biopsies were included in the study. Squamous cell carcinoma was the commonest histologically diagnosed lesion accounting for 70(32.6%) cases of all lesions and 77.8% of all malignancies. The second commonest lesion and the most frequent benign pathology is the Condyloma acuminatum (viral warts) which accounted for 41(19.1%) cases. The age bracket 20 to 59 years constituted 79.5% of cases (171 cases). The age range, mean, median, and mode in years were 5.0-85.0, 39.5+15.9, 38.0, and 50.0 respectively. CONCLUSION: Squamous cell carcinoma and veneral warts are the commonest lesions of the vulva and vagina in our environment. Robust vaccination programs against the etiological agent, the human papilloma virus is highly recommended.

INTRODUCTION: La vulve et le vagin ont une importance considérable pour la féminité en raison des myriades de fonctions spécialisées qu'ils remplissent. Les maladies de cet organe ont des ramifications physiques, sociales, mentales et psychologiques. L'objectif de ce travail est d'étudier le modèle pathologique et la présentation clinique des maladies de la vulve et du vagin au département de pathologie anatomique et de médecine légale de l'hôpital universitaire de Jos entre le 1er janvier 2011 et le 31 décembre 2020. METHODOLOGIE: Cette étude est descriptive de tous les cas de lésions vulvaires et vaginales diagnostiquées histologiquement au Centre. Le diagnostic histologique, les données biologiques et les informations cliniques des patientes ont été extraits des dossiers médicaux. Les données obtenues ont été analysées et présentées dans des tableaux sous forme de fréquences simples, de pourcentages, d'intervalles et de mesures de tendances centrales. RÉSULTATS: Deux cent quinze biopsies vulvaires et vaginales ont été incluses dans l'étude. Le carcinome épidermoïde était la lésion histologiquement diagnostiquée la plus fréquente, représentant 70 (32,6 %) cas de toutes les lésions et 77,8 % de toutes les tumeurs malignes. La deuxième lésion la plus fréquente et la pathologie bénigne la plus fréquente est le condylome acuminé (verrues virales), qui représente 41 (19,1 %) cas. La tranche d'âge de 20 à 59 ans représentait 79,5 % des cas (171 cas). La fourchette d'âge, la moyenne, la médiane et le mode en années étaient respectivement de 5,0-85,0, 39,5+15,9, 38,0 et 50,0. CONCLUSION: le carcinome épidermoïde et les verrues générales sont les lésions les plus fréquentes de la vulve et du vagin dans notre environnement. Des programmes de vaccination robustes contre l'agent étiologique de cette pathologie, le virus du papillome humain, sont fortement recommandés. Mots clés: Vulve, Vagin, Cancer, Verrue.

Squamous Cell Carcinoma of the Foot Occurring in a Wart.

Verrucous carcinoma is a rare form squamous cell carcinoma which appears similar to a wart. When it occurs in the feet, it can be easily misdiagnosed. It rarely metastasizes or recurs posttreatment. We report a case of a septuagenarian with recurrence of verrucous carcinoma diagnosed within 6 months at the site of previous treatment. Unique features in our patient's clinical presentation include his advanced age, being nondiabetic, and the rapid recurrence of carcinoma.Level of Evidence: Level IV: Case report.

Cantharidin-Podophyllin-Salicylic Acid Formulation as a First-Line Treatment for Plantar Warts? A Case Report with Multiple Plantar Warts of Human Papillomavirus Biotype 27 and Previous Failed Treatments.

BACKGROUND Plantar warts are benign skin tumors caused by the human papillomavirus (HPV). There are multiple treatments, but none ensure absolute success. Successful treatment depends on several factors, such as the location, number of lesions, HPV biotype, and the patient's health condition. This report presents a 53-year-old woman who had multiple recalcitrant plantar warts with HPV biotype 27 that were treated using a cantharidin-podophyllin-salicylic acid (CPS) formulation after 2 failed treatments. CASE REPORT A 53-year-old woman was seen on October 25, 2021. She had 6 plantar warts due to HPV biotype 27, which was confirmed by polymerase chain reaction using a sample of hyperkeratosis scales obtained from the wart after debridement. Five cryotherapy sessions were applied, without clinical improvement. Two sessions of nitric-acid-zinc complex were then applied, from which the patient reported severe pain, without clinical improvement. Finally, 3 sessions of CPS formulation were applied, and the HPV remitted in all warts. CONCLUSIONS Conservative treatments, such as cryotherapy, have not been effective in a case of multiple recalcitrant plantar warts. The combined action of the 3 compounds of CPS formulation was key in the resolution of this case. Plantar wart treatment should be easy to apply, effective, fast, and efficient. In cases of recalcitrant or numerous warts, treatment should be more aggressive from the beginning if the patient's lifestyle allows it. It would be interesting to conduct randomized clinical trials to find out which patients could be indicated for the CPS formulation as a first line of treatment.

Intralesional combined furosemide and digoxin in cutaneous warts treatment: A randomized controlled clinical trial.

Although being a benign lesion, Warts can affect the quality of life by causing discomfort, disfigurement, and social embarrassment besides the tendency to spread. Cutaneous wart treatment faces many challenges as the development of an antiviral drug that can eradicate the human papilloma virus (HPV) is difficult. This clinical study aimed to assess the efficacy and safety of intralesional combined furosemide and digoxin in the treatment of multiple cutaneous warts. This double blinded randomized clinical trial included 80 adult patients with multiple cutaneous warts (≥2 warts) who were randomized into two groups, Group I (40 patients) treated with intralesional combined furosemide and digoxin and Group II (40 patients) who were treated with intralesional normal saline solution as a control group, weekly till improvement or for maximum five sessions. Clinical and dermoscopic evaluation at baseline, every session, and monthly for 6 months after the last session to detect any recurrence was performed. Complete wart clearance was observed in 92.5% of patients in the intralesional combined furosemide and digoxin group (Group I) compared with 10.0% in saline group (Group II), with highly statistically significant difference (P-value = 0.000). Pain during injection in 95.0% and 45.0% of patients in Group I and Group II respectively, treatment group was superior compared to control group. Intralesional injection of combined furosemide and digoxin can be a safe and effective treatment option in multiple cutaneous warts with minimal side effects in this study.

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

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.

Clinical guideline for the diagnosis and treatment of cutaneous warts (2022).

AIM: Cutaneous warts caused by human papillomavirus are benign proliferative lesions that occur at any ages in human lives. Updated, comprehensive and systematic evidence-based guidelines to guide clinical practice are urgently needed. METHODS: We collaborated with multidisciplinary experts to formulate this guideline based on evidences of already published literature, focusing on 13 clinical questions elected by a panel of experts. We adopted Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to form classification of recommendations as well as the improved Delphi method to retain respective recommendations with a consensus degree of over 80%. RESULTS: Our guideline covered aspects of the diagnosis and treatment of cutaneous warts such as diagnostic gold standard, transmission routes, laboratory tests, treatment principle, clinical cure criterion, definitions, and treatments of common warts, flat warts, plantar warts, condyloma acuminatum, and epidermodysplasia verruciformis. Recommendations about special population such as children and pregnant women are also listed. In total, 49 recommendations have been obtained. CONCLUSIONS: It is a comprehensive and systematic evidence-based guideline and we hope this guideline could systematically and effectively guide the clinical practice of cutaneous warts and improve the overall levels of medical services.

Genotype-phenotype correlations in WHIM syndrome: a systematic characterization of CXCR4WHIM variants.

Warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome is a rare primary immunodeficiency predominantly caused by heterozygous gain-of-function mutations in CXCR4 C-terminus. We assessed genotype-phenotype correlations for known pathogenic CXCR4 variants and in vitro response of each variant to mavorixafor, an investigational CXCR4 antagonist. We used cell-based assays to analyze CXCL12-induced receptor trafficking and downstream signaling of 14 pathogenic CXCR4 variants previously identified in patients with WHIM syndrome. All CXCR4 variants displayed impaired receptor trafficking, hyperactive downstream signaling, and enhanced chemotaxis in response to CXCL12. Mavorixafor inhibited CXCL12-dependent signaling and hyperactivation in cells harboring CXCR4WHIM mutations. A strong correlation was found between CXCR4 internalization defect and severity of blood leukocytopenias and infection susceptibility, and between AKT activation and immunoglobulin A level and CD4+ T-cell counts. This study is the first to show WHIM syndrome clinical phenotype variability as a function of both CXCR4WHIM genotype diversity and associated functional dysregulation. Our findings suggest that CXCR4 internalization may be used to assess the pathogenicity of CXCR4 variants in vitro and also as a potential WHIM-related disease biomarker. The investigational CXCR4 antagonist mavorixafor inhibited CXCL12-dependent signaling in all tested CXCR4-variant cell lines at clinically relevant concentrations.

Verrucous Skin Lesions on the Feet in Diabetic Neuropathy in the Context of Podiatric Practice - Our Pilot Experiences.

Skin changes in patients with diabetic foot (DF) are relatively common. The most frequent lesions feature papillae or cilia of various forms. The condition known as "verrucous skin lesions on the feet in diabetic neuropathy" (VSLDN) occurs in patients with distal diabetic sensorimotor neuropathy and is commonly located in places of high mechanical pressure. However, there is a scarcity of published data on the diagnosis and treatment of VSLDN. Our paper describes various types of VSLDN skin pathology, summarizes the diagnostic procedure options available, and documents the experience of our diabetic foot clinic in applying short-term VSLDN therapies as part of routine podiatric practice.

Mucinous Syringometaplasia: Case Report and Review of the Literature.

ABSTRACT: Mucinous syringometaplasia is a rare and poorly recognized entity that usually presents as a warty tumor in acral regions. It is more frequent in men, and the age of presentation is variable. Typically, it has been reported as a solitary lesion with a warty appearance that occasionally can drain serous material. The affected sites include head, neck, breast, acral regions, and buttocks. The evolution over time is variable. The pathogenesis has not been elucidated. Diagnosis is established through histopathology, the characteristic feature is an epidermal invagination, which creates a structure similar to a "pore" at the dermal level. The clinical differential diagnosis is mainly with a viral wart, but it can also resemble basal cell carcinomas and other adnexal tumors. The treatment is surgical, and no recurrences have been reported to date. We describe the case of a 25-year-old woman who presented with a lesion on one of her eyelids. A shave removal of the lesion was performed, and the diagnosis was established by histopathologic examination.

Plerixafor on a WHIM - Promise or Fantasy of a New CXCR4 Inhibitor for This Rare, but Important Syndrome?

Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) is a primary immunodeficiency syndrome. Patients with WHIM syndrome are more susceptible to human papillomavirus (HPV) infections and commonly present to a dermatologist with recalcitrant to treatment warts. Other cardinal features of WHIM syndrome include recurrent sinopulmonary bacterial infections, neutropenia/lymphopenia, low levels of immunoglobulins (IgG, IgA, IgM) and myelokathexis. Research demonstrated that truncating gain-of-function mutations of the C-X-C chemokine receptor type 4 gene (CXCR4) are responsible for this disease. Plerixafor, a specific small molecule antagonist of CXCR4, is currently used for peripheral blood hematopoietic stem cell (HSC) mobilization in stem cell transplant recipients. It has recently shown promise for the treatment of WHIM syndrome in phase I/II clinical trials. In this paper we review the emerging patient clinical data for this medication and highlight the role of CXCR4 in other important skin diseases including keratinocyte carcinomas, psoriasis and cutaneous T-cell lymphoma.

Recalcitrant Cutaneous Warts in a Family with Inherited ICOS Deficiency.

Recalcitrant warts, caused by human papillomaviruses (HPVs), can be a cutaneous manifestation of inborn error of immunity. This study investigated the clinical manifestations, immunodeficiency, single-gene susceptibility, and HPV repertoire in a consanguineous family with severe sinopulmonary infections and recalcitrant warts. Clinical and immunologic evaluations, including FACS and lymphocyte transformation test, provided evidence for immunodeficiency. Combined whole-exome sequencing and genome-wide homozygosity mapping were utilized to disclose candidate sequence variants. Whole-transcriptome sequencing was used to concomitantly investigate the HPV genotypes and the consequences of detected sequence variants in the host. The proband, a male aged 41 years, was found to be homozygous for the c.6delG, p.Lys2Asnfs∗17 variant in ICOS, encoding the inducible T-cell costimulator. This variant was located inside the 5 megabase of runs of homozygosity on 2q33.2. RNA sequencing confirmed the deleteriousness of the ICOS variant in three skin biopsies revealing significant downregulation of ICOS and its ligand, ICOSLG. Reads unaligned to the human genome were applied to 926 different viruses, and α-HPV57, ß-HPV107, ß-HPV14, and ß-HPV17 were detected. Collectively, we describe a previously unrecognized inborn error of T-cell immunity to HPVs, indicating that autosomal recessive ICOS deficiency can underlie recalcitrant warts, emphasizing the immunologic underpinnings of recalcitrant warts at the nexus of human and viral genomic variation.

Combined Poroma and Verruca Plantaris.

ABSTRACT: A 76-year-old female patient presented with a peculiar new exophytic-appearing, flesh-colored skin lesion on her left hallux. Owing to its atypical appearance, the neoplasm was biopsied. Histologic sections demonstrated numerous thickened, anastomosing cord-like structures composed of bland appearing adnexal keratinocytes attached to the epidermis and extending into the superficial dermis. Nearby areas exhibited papillomatosis, epidermal acanthosis, dense hyperparakeratosis, hypergranulosis, and superficial koilocytes, findings consistent with a verruca plantaris. A p16 stain was positive in many of the superficial epidermal keratinocytes. Human papillomavirus typing by in situ hybridization for the most common low-risk and high-risk types was also performed and was negative for these. We herein present an unusual case of a skin lesion which combines features of a poroma with a verruca plantaris. We further review what is known of the relationship between human papillomavirus and poroid neoplasms.

Dermatologists' Impressions of Spontaneously Regressing Verruca Plana Histopathology.

ABSTRACT: Verruca plana in its regressing phase exhibits clinical and histological features distinct from classic verruca plana, but the ways in which these features should inform treatment plans are still under investigation. We conducted a retrospective single-center analysis of 25 patients with features of classic verruca plana, or plane warts, who exhibited self-remission within 4 weeks of skin biopsy. Measures included lesion sites, clinical findings preceding regression, and histological analysis. Histological analysis involved review by 2 dermatologists followed by impressions given by 4 board-certified dermatologists who were blinded to the clinical characteristics of the patients. Histopathological findings of regressing plane warts showed superficial perivascular infiltration (96%), spongiosis and exocytosis (84%), basal vacuolization (64%), parakeratosis (64%), apoptotic keratinocytes (60%), and lichenoid infiltration (44%). These findings were more compatible with the histological patterns of pityriasis lichenoides, lichen planus, and spongiotic eczema, rather than classic verruca plana. This suggests that regressing verruca plana may be included in the differential diagnosis of lesions exhibiting a lichenoid or spongiotic reaction, and observation may be a favorable treatment plan in these patients.

Diagnostic techniques in HPV infections and the need to implement them in plantar lesions: A systematic review.

INTRODUCTION: Human papillomavirus has been reported as the etiological cause of most cervical cancers and other potentially malignant lesions. It also affects other areas, producing benign tumors on the skin. Plantar warts are a common problem found in clinical practice and share signs and symptoms with other dermatological conditions. Diagnosis of HPV infection remains a hot topic in research. METHOD: The present work systematically reviews the literature on the diagnostic techniques available in the clinical setting for any type of lesion produced by the virus and compares the techniques identified to those found in use for foot lesions. RESULTS: Results showed a variety of diagnostic methods, including molecular techniques, which exhibit more sensitivity than other methods but are less frequently applied to plantar lesions, where visual inspection is the most frequent method but can lead to errors. CONCLUSION: The techniques identified need to be applied to plantar lesions to improve differential diagnosis in clinical practice. EXPERT OPINION: Research will continue to grow and a proper diagnostic technique for plantar lesions will be available in the near future.