Dysregulation of autophagy-associated microRNAs in condyloma acuminatum.

Condyloma acuminatum, which is caused by low-risk human papillomavirus (lrHPV) infection, is one of the most common sexually transmitted diseases. Autophagy is thought to be associated with condyloma acuminatum, but how the autophagy process is regulated remains unclear. MicroRNAs (miRNAs) are important regulators of gene transcription that play a central role in many biological processes, including autophagy and viral infection. This study was designed to identify autophagy-related miRNAs and their targets in condyloma acuminatum and to validate their expression. The levels of the autophagy proteins microtubule-associated protein 1 light chain 3 (LC3) and P62/SQSTM1 (P62) were abnormally increased in the local lesion tissue of condyloma acuminatum patients compared with healthy controls. MiRNAs and their target mRNAs in condyloma acuminatum patients were analyzed by bioinformatics. Eighty-one differentially expressed miRNAs were identified, of which 56 were downregulated and 25 were upregulated. Two of the differentially expressed miRNAs associated with autophagy, miRNA-30a-5p and miRNA-514a-3p, were analyzed further, and their target genes were identified as autophagy-related protein (Atg) 5 and Atg12 and Atg3 and Atg12, respectively. The expression levels of miRNA-30a-5p and miRNA-514a-3p were decreased and those of Atg5, Atg12 and Atg3 were increased in condyloma acuminatum patients compared with healthy controls. In addition, miRNA-30a-5p and miRNA-514a-3p expression correlated with the proliferation index Ki-67 in condyloma acuminatum. Taken together, our results suggest that the changes in autophagy levels in patients with condyloma acuminatum may be related to the changes in miRNA-30a-5p and miRNA-514a-3p expression. This study provides a theoretical basis for identifying new mechanisms that link miRNAs, HPV infection and host autophagy in vivo.

Anogenital Papular Lesions in Children Five Year Old and Younger: Gender Differences.

INTRODUCTION: Anogenital area is a small compartment in the human body. Recognition of various dermatological conditions affecting this area in children is essential for any physician involved in pediatric examination and evaluation. AIM: To assess the nature, diagnoses, and gender differences of Anogenital lesions in pediatric patients presented to Royal Medical Services (RMS) general dermatology clinics, who were five year old and younger. METHODS: The authors reviewed patients' medical records in the period between September 2015 and September 2018. The inclusion criteria were children of both genders who were five year old or younger and presented with papular lesions in the Anogenital area. Those patients visited the general dermatology clinics of The Royal Medical Services Hospitals from the Eastern and Southern regions of Jordan. RESULTS: Over a period of 3 years, a total of 514 patients were five year old or younger presented with various Anogenital papular lesions were evaluated and treated in general dermatology clinics. 35% of the patients presented with Perianal Psuedoverrucous Papules and nodules, 21% presented with Anogenital warts, 16% presented with Molluscum Contageosum. Moreover, 10% were presented with Epidermal nevi, 6% presented with Pearly Penile Papules, 7% presented with Infantile Perineal Pyramidal Protrusion, 4% presented with Vulvar Vestibular Papillomatosis, 0.2% presented with Juvenile Xanthogranuloma, 0.2% presented with lymphangioma Circumscriptum, and 0.2% presented with median raphe cyst. In addition, gender differences were noticed among Genital Warts, Mollascum Contageosum, Pearly Penile Papules, and Vulvar Vestibular Papillomatosis. CONCLUSION: Anogenital papules in children have variable clinical presentations and can be caused by multiple number of infectious and non-infectious factors. The presence of such lesions can be a source of a major concern for parents, and might be mistakenly assumed as a result of sexual assaults. Proper recognition of these papules is of paramount importance for all physicians involved in children examination, to appropriately reassure parents and avoid unnecessary investigations and psychological distress.

Yes-Associated Protein Promotes the Development of Condyloma Acuminatum through EGFR Pathway Activation.

OBJECTIVE: Investigate the role of Yes-associated protein (YAP1) in the development of condyloma acuminatum (CA). METHODS: We enrolled 30 male patients with CA and 20 healthy individuals as a control group, to compare the YAP1 expression in their tissue samples. Following this, we overexpressed and downregulated YAP1 expression in HaCaT cells to examine the migratory, proliferative, and apoptotic potential of HaCaT cells expressing different levels of YAP1. RESULTS: In the CA patient tissue samples, an increase in YAP1 expression can be observed. In vitro,the overexpression of YAP1 was shown to promote the growth and migration of HaCaT cells and to activate epidermal growth factor receptor (EGFR) pathway-associated proteins, while the downregulation of YAP1 inhibited cell growth and migration of these cells. CONCLUSIONS: YAP1 promotes the growth of keratinocytes in CA through the activation of the EGFR pathway, and it may mediate the development of human papilloma virus-associated diseases.

Possible role of interleukin 21 and interleukin 33 in patients with genital warts.

Genital warts (GWs) are most prevalent sexually transmitted infections, presenting especially among the sexually active young population of both sexes. Efficient cell-mediated immunity is needed for regression of GWs. To clarify the reactivity of cellular immunity among patients with GWs by means of measurements of their levels of serum interleukin (IL)-21 and IL-33, hence, to identify the possible role of IL-21 and IL-33 in GWs, this study aimed to evaluate serum levels of IL-21 and IL-33 among patients with GWs in comparison with the results of the controls. Levels of serum IL-21 and IL-33 were assayed utilizing commercially enzyme-linked immune-sorbent assay kits in 45 patients with GWs and 45 healthy control subjects. Levels of serum IL-21 and IL-33 were significantly decreased among patients with GWs in comparison with the controls (p < .0001). There was a highly significant positive correlation between IL-21 and IL-33 (r = .73, p < .0001). Low levels of serum IL-21 and IL-33 could have a contributive role in development, persistence, severity, and recurrence of GWs which rely basically on the defectiveness of cell-mediated immunity. This could receive new light on nonconventional strategies for the prospective medical therapies of GWs by means of regulation of IL-21 and IL-33.

Proteomic and bioinformatic analysis of condyloma acuminata: mild hyperthermia treatment reveals compromised HPV infectivity of keratinocytes via regulation of metabolism, differentiation and anti-viral responses.

BACKGROUND: Hyperthermia has proved successful in treating cutaneous human papillomavirus infectious diseases such as plantar wart and condyloma acuminata (CA). Moreover, this treatment provides improved therapeutic efficacy in these conditions as compared with conventional therapies. OBJECTIVES: To investigate the global proteome changes in CA in response to hyperthermia and achieve a better understanding of the mechanisms of hyperthermia therapy against HPV-infectious diseases. METHODS: CA tissue was obtained from patients undergoing pathological examinations. Diagnosis was verified as based on results of both HE staining and HPV-DNA PCR assay. Hyperthermia was achieved with a 44 °C water bath. Differentially expressed proteins (DEPs) were identified by iTRAQ labeling, SCX chromatography and LC-MS/MS assay. Validation of proteomic results was performed using real-time qPCR and western blot, while bioinformatic analysis of DEPs was accomplished by R 3.4.1, STRING and Cytoscape softwares. RESULTS: In response to hyperthermia, a total of 102 DEPs were identified with 37 being upregulated and 65 downregulated. Among these DEPs, hyperthermia induced proteins involved with anti-viral processes such as OAS1, MX1, BANF1, CANX and AP1S1, whereas it inhibited proteins that participated in cellular metabolism, such as GALT, H6PD, EXOSC4 and EXOSC6; protein translation, such as RPS4Y1; as well as keratinocyte differentiation, such as KRT5, KRT27, KRT75, KRT76 and H2AFY2. CONCLUSIONS: Hyperthermia inhibited enzymes and molecules responsible for metabolism modulation and keratinocyte differentiation in CA tissue, whereas it promoted factors involved in anti-viral responses. Such effects may, in part, contribute to the efficacy of local hyperthermia therapy against HPV infection.

Human papillomatosis genotyping and severity in patients with recurrent respiratory papillomatosis.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is caused by human papilloma virus (HPV) and is the most common benign laryngeal neoplasm in children. Although RRP is rarely fatal, the disease requires prolonged, extensive medical and surgical treatment, leading to physical and emotional suffering in affected children and their families. Previous studies show HPV type 11 and type 6 in the lesion of Thai subjects with RRP. There is currently no published data available from Thailand that compares staging and severity with RRP genotypes. OBJECTIVE: To identify the genotypes of human papilloma virus (HPV) isolated from patients with RRP and compare the staging and severity with human papilloma virus genotype. MATERIAL AND METHOD: This prospective study was designed to assess population characteristics and follow the clinical course of RRP from January 2011 to January 2013. At each endoscopic evaluation or debridement, all surgeons to stage each patient's disease severity used a consistent scoring system. The samples were analyzed for HPV genotype. RESULTS: Fifteen Thai children (7 female, 8 male) with respiratory papillomatosis were enrolled. Results showed that HPV type 6 and HPV type 11 caused RRP in 6 (40%) and 9 (60%) of the children, respectively. No co-infection between HPV type 6 and type 11 was found. Overall mean age at diagnosis of patients with RRP was 2.65 ± 0.82 years. The age at diagnosis was significantly different between both HPV genotypes (p = 0.008). The mean disease severity score for HPV type 6 infection was 13.83 ± 9.94, and that of HPV type 11 infection was 27.44 ± 8.24. The mean disease severity score of HPV type 11 infection was significantly higher than that of HPV type 6 infection (p = 0.013). CONCLUSION: HPV type 6 and type 11 caused RRP in Thai children. RRP attributable to infection with HPV type 11 is more aggressive in disease severity and has a shorter life time than HPV type 6 at time of first diagnosis. RRP is an incurable disease that requires long-term medical management. Improved awareness and understanding amongst the Thai population should be promoted to limit the spread of the disease. In addition, further research on the treatment of RRP would benefit patients.

Management of external genital warts.

Genital warts affect 1% of the sexually active U.S. population and are commonly seen in primary care. Human papillomavirus types 6 and 11 are responsible for most genital warts. Warts vary from small, flat-topped papules to large, cauliflower-like lesions on the anogenital mucosa and surrounding skin. Diagnosis is clinical, but atypical lesions should be confirmed by histology. Treatments may be applied by patients, or by a clinician in the office. Patient-applied treatments include topical imiquimod, podofilox, and sinecatechins, whereas clinician-applied treatments include podophyllin, bichloroacetic acid, and trichloroacetic acid. Surgical treatments include excision, cryotherapy, and electrosurgery. The quadrivalent human papillomavirus vaccine is active against virus subtypes that cause genital warts in men and women. Additionally, male circumcision may be effective in decreasing the transmission of human immunodeficiency virus, human papillomavirus, and herpes simplex virus.

An overview of genital warts.

Genital warts are a common sexually transmitted infection that is particularly prevalent in young people. Although the warts are usually painless and rarely cause any long-term health problems, they can cause significant psychological distress and relationship problems for those affected. This article provides an overview of genital warts to enable nurses to guide people in the prevention and treatment of the infection.

Relación entre condilomas acuminados y cáncer de pene y ano / Relation between condylomata acuminata and penis cancer and anus cancer

Se señala que existen más de 200 genotipos de virus de papiloma humano, de ellos más de 40 se han aislado en el tracto genital inferior. La manifestación clínica son los condilomas acuminados, que son generalmente causados por virus de papiloma humano de bajo riesgo, pero son un importante indicador de infección por virus de alto riesgo. La infección por este virus ha sido demostrada en el carcinoma epidermoide de pene y ano. Objetivo: determinar la relación entre condilomas acuminados y cáncer de pene y ano.Métodos: se realizó un estudio observacional, descriptivo y transversal cuyo universo fueron todos los pacientes con condilomas acuminados que asistieron a las consultas de Dermatología y Urología del Hospital Universitario Manuel Ascunce Domenech, de la provincia de Camagüey, desde 1ero de enero al 31 de diciembre de 2011. Se aplicó ácido acético al 5 por ciento para la detección subclínica de condilomas acuminados, se realizó citología uretral a los enfermos que presentaban lesiones de pene, y anal a aquellos que tenían lesiones anales. Se realizó biopsia de pene y uretroscopia a aquellos con citología uretral sospechosa de células neoplásicas, y biopsia de ano y anoscopia en los que la citología anal fue sospechosa de células neoplásicas. La información obtenida fue procesada mediante el programa estadístico SPSS-10. Los métodos empleados fueron estadística descriptiva de distribución de frecuencias absolutas y relativas. Los resultados del estudio se expusieron en tablas (AU)

There are 200 genotypes of human papillomaviruses, more than 40 of them have isolated in the lower genital tract. They are subclassified according to the oncogenic capacity in low-risk and high-risk. The clinical manifestation is condylomata acuminata that are generally caused by low-risk human papillomaviruses but constitute an important indicator of infection by high-risk viruses. Infection caused by this virus has been proved in the penis and anus squamous carcinoma.Objective: to determine the relation between condylomata acuminata and penis cancer and anus cancer.Methods: a cross-sectional, descriptive, observational study was conducted. The universe was composed of all the patients with condylomata acuminata that assisted to the consultations of Dermatology and Urology of the Manuel Ascunce Domenech University Hospital of Camagüey, from January 1st to December 31st, 2011. For the subclinical detection of condylomata acuminata, 5 porcent acetic acid was applied; urethral cytology was made to all the patients who presented lesions in the penis and anal cytology in those patients with lesions in the anus. Penis biopsy and ureteroscopy was made to the patients that presented urethral cytology with suspicions of neoplastic cells; anus biopsy and anoscopy was made to those patients whose anal cytology showed suspicions of neoplastic cells. The information obtained was processed through the statistical program SPSS-10. The method applied was the descriptive statistics of distribution of absolute and relative frequencies. The results of the study were showed in tables (AU)

Pharmacokinetics of daily self-application of imiquimod 3.75% cream in adult patients with external anogenital warts.

Imiquimod 3.75% cream is a new formulation intended for daily self-application. The objective of this study was to characterize serum imiquimod pharmacokinetics under maximal use conditions. Adults with ≥8 warts or total wart area ≥100 mm² applied up to 1 packet of imiquimod 3.75% cream (250 mg cream, 9.375 mg imiquimod) once daily for 3 weeks. Blood was obtained prior to doses 1, 7, 14, and 21 and at selected time points after doses 1 and 21. Eighteen patients (13 men and 5 women) with a median wart count of 16 and total wart area of 60 mm² were enrolled. Day 21 mean (SD) serum C(max) was 0.49 (0.37) ng/mL, AUC0₋24 6.80 (3.59) ng·h/mL, and t(1/2) 24.1 (12.4) hours. Steady state was achieved by day 7 with ~2-fold increase in C(max) and AUC after multiple dosing. Overall, C(max) was higher and t(max) shorter in women, with comparable AUC0₋24. Imiquimod metabolites were sporadically quantifiable. No patients discontinued for adverse events; 1 interrupted dosing for an application site ulcer. Treatment-related adverse events occurred in 16.7% of the patients. In conclusion, serum imiquimod concentrations were low after daily self-application to external anogenital warts of up to 1 packet of imiquimod 3.75% cream for 21 days.

Evaluating the epidemiology and morbidity burden associated with human papillomavirus in Israel: accounting for CIN1 and genital warts in addition to CIN2/3 and cervical cancer.

BACKGROUND: Human papillomavirus (HPV) infection is mostly associated with cervical cancer (CC). However, it can cause other illnesses as well, all of which impact on people's wellbeing and consume healthcare resources. Measures for prevention or early detection of these conditions differ in their effectiveness and cost. An informative evaluation of the projected benefit of these measures depends on understanding the current unmet need, not only limited to CC. OBJECTIVE: To evaluate the burden of HPV-related conditions in Israel, including CC, cervical precancerous lesions and genital warts. METHODS: A retrospective database analysis was conducted for the second largest health management organization (HMO) in Israel, covering approximately 1.8 million people. Records were drawn following a search for key words indicative of related diagnoses, lab results, medications, or procedures for the time period of 2006-2008. Prevalence, incidence and resource utilization were analysed. Findings were extrapolated to the whole Israeli population using age and gender incidence rates. RESULTS: Incidence of CC was found to be 5 per 100,000 females. Incidences of cervical intraepithelial neoplasia (CIN) grades 1, 2 and 3 were 74, 27 and 36 per 100,000 females, respectively. Incidence of genital warts was 239 and 185 per 100,000 for men and women, respectively. The overall annual economic burden was calculated to be $US48,838,058 (year 2010 values). CONCLUSIONS: HPV poses a significant burden in terms of health (clinical and quality of life) and in monetary terms, even for conditions that are sometimes regarded as benign, such as CIN1 or genital warts. Current findings should be used for proper evaluation of measures to reduce HPV-related morbidity and mortality, such as regular screening and vaccination.

Health related quality of life in patients with anogenital warts.

INTRODUCTION: The health-related quality-of-life (HRQoL) instruments are an important tool for the evaluation of medical outcomes. Sexually transmitted diseases (STDs) influence the patients' life. We aimed to evaluate the HRQoL in patients with anogenital warts at the time of and 1 month after the diagnosis. MATERIALS AND METHODS: We used the short-form (SF)-36 questionnaire to compare the HRQoL of 91 patients with anogenital warts to 53 control subjects with the same socioeconomic characteristics. RESULTS: There was no statistical difference in the overall HRQoL measurement between the anogenital wart patients and controls. However, there was an improvement in the scales of vitality (65.22 ± 15.70 vs. 69.04 ± 14.11, respectively; p < 0.05) and mental health (65.00 ± 20.09 vs. 69.43 ± 18.08, respectively; p < 0.05) in anogenital warts patients between the time of diagnosis and 1 month later. Furthermore, there was a significant deterioration in the scale of social functioning (73.47 ± 22.18 vs. 72.89 ± 19.28, respectively; p < 0.05). The small sample size is a limitation of our study. CONCLUSIONS: HRQoL does not appear to be influenced in anogenital wart patients, as measured by the generic instrument SF-36. It is therefore important to develop specific instruments for the measurement of HRQoL in this group of patients.

Appraisal of the burden of genital warts from a healthcare and individual patient perspective.

OBJECTIVE: Worldwide, genital warts, caused by human papillomavirus (HPV) is a common, sexually transmitted disease. The overall disease management strategy for genital warts should be determined not only by the prevalence, but also by the impact of the disease on individuals and society. The purpose of this study was therefore to investigate the epidemiological, economic and quality of life (QoL) burden of genital warts. METHODS: A systematic literature review was conducted on the epidemiology, QoL and management cost of genital warts in the USA, UK and France, based on studies published between 1998 and 2008. Due to scarcity of data, all studies reporting standardized QoL assessments among patients with genital warts were utilized, regardless of country of origin. Original studies were preferred over information cited in review articles. RESULTS: Data from three countries suggest that genital warts occur in 0.06-0.23% of the population each year. Despite the fact that spontaneous remissions occur frequently (up to 40%), patients often prefer immediate treatment. While treatment can be costly in absolute terms (€163-510 per treatment episode), these costs are lower compared with other sexually transmitted infections (STIs). Modest reductions in QoL have been noted, which may be mitigated through adequate patient education and support. CONCLUSIONS: While genital warts are an inconvenience for many patients, the occurrence may be lower than often quoted in the literature, and the economic burden on society is less than for other prominent STIs. However, concerted efforts to establish improved data collection and surveillance systems are needed in order to accurately define the burden of genital warts on individuals and society.

Condiloma acuminado gigante (tumor de Buschke-Löwenstein) / Giant condyloma acuminata (Buschke-Löwenstein tumour)

Los condilomas o verrugas genitales son producidos por el virus del papiloma humano. La infección típicamente ocurre cuando las células basales del huésped se exponen a la infección viral a través de una barrera epitelial dañada, como sucede durante el acto sexual o como producto de otras abrasiones dérmicas menores. Se necesita la presencia de otros factores asociados para producir la enfermedad, como son: promiscuidad sexual, mala nutrición, tabaquismo, multiparidad, depresión del sistema inmunológico y uso prolongado de anticonceptivos orales. Los condilomas acuminados constituyen una de las enfermedades de transmisión sexual más frecuentes y se vinculan, por lo general, con los tipos de cepas 6 y 11. En pocas ocasiones pueden evolucionar como un tumor invasivo con malignidad local, aunque sin metástasis, equivalente a un carcinoma verrucoso: es el síndrome de Buschke-Löwenstein (AU)

Condylomata or genital warts are produced by the human papilloma virus (HPV). The infection occurs typically when the basal cells of the host are exposed to the viral infection due to a damaged epithelial barrier, as happens during the sexual act or in minor skin abrasions. Other associating factors are required to produce the disease, such as: inappropriate sexual behaviour, smoking, malnutrition, multiparity, immune system depression and prolonged use of oral anticonceptives. Condyloma acuminatum is one of the most frequent sexual transmitted diseases and is generally associated with types HPV 6 and 11. On some occasions, it can progress to a local invasive tumor but without metastases, similar to a verrucous carcinoma: it is the Buschke-Löwenstein syndrome (AU)

A practical approach to warts in the emergency department.

Although cutaneous warts are one of the most common skin conditions affecting children, their management can be challenging, especially in complex cases and even more so during a single emergency department encounter. Anogenital warts require particular attention because of their possible but nonspecific association with sexual abuse. This review will focus on cutaneous warts and anogenital warts, with a discussion of their recognition and treatment, especially in the emergency department. The medicolegal implications of anogenital warts in children are also reviewed.

Resolución de condilomas acuminados recalcitrantes en un paciente infectado por el virus de la inmunodeficiencia humana tratado con cidofovir tópico / Resolution of recalcitrant condyloma acuminata in a patient with human immunodeficiency virus treated with cidofovir

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New viral vaccines for dermatologic disease.

UNLABELLED: Two new viral vaccines have recently been approved by the Food and Drug Administration. Human papillomavirus (HPV) vaccine is intended to reduce infection with the most common HPV types that cause anogenital disease, including cervical cancer and genital warts. Herpes zoster (HZ) vaccine is intended to prevent shingles and its complications. The use of these two vaccines will immediately begin to impact dermatologic practice throughout the world and will reduce the healthcare burden associated with the diseases caused by the two viruses. The following review summarizes the relevant pathophysiology and epidemiology of genital warts, cervical neoplasia, and herpes zoster and describes the recent trials that have demonstrated efficacy and safety of the HPV and HZ vaccines. LEARNING OBJECTIVES: Following the completion of this learning activity, the participant will be able to describe the mechanisms of HPV and varicella zoster virus infection as well as pathogenesis, identify key aspects of the immune system involved in clearing the infection, and prescribe HPV and HZ vaccines for prevention of disease.