The approach to children with anogenital warts in the context of sexual abuse is a challenge in clinical practice. This study aims to review the current knowledge of anogenital warts in children, the forms of transmission, and the association with sexual abuse and to propose a cross-sectional approach involving all medical specialties. A systematic review of the literature was conducted in Portuguese and English from January 2000 to June 2016 using the ISI Web of Knowledge and PubMed databases. Children aged 12 years or younger were included. The ethical and legal aspects were consulted in the Declaration and Convention on the Rights of Children and in the World Health Organization. Non-sexual and sexual transmission events of human papillomavirus in children have been well documented. The possibility of sexual transmission appears to be greater in children older than 4 years. In the case of anogenital warts in children younger than 4 years of age, the possibility of non-sexual transmission should be strongly considered in the absence of another sexually transmitted infection, clinical indicators, or history of sexual abuse. The importance of human papillomavirus genotyping in the evaluation of sexual abuse is controversial. A detailed medical history and physical examination of both the child and caregivers are critical during the course of the investigation. The likelihood of an association between human papillomavirus infection and sexual abuse increases directly with age. A multidisciplinary clinical approach improves the ability to identify sexual abuse in children with anogenital warts.

Warts are a common skin problem and are caused by infection with a virus. Warts are currently mainly treated by therapies involving ablating tissue or interrupting cellular division. However, all these existing treatments are either invasive or cause skin pain and tissue destruction. Imiquimod is a synthetic compound that belongs to the imidazoquinolinone family. It has been successfully used as a topical drug to treat external anogenital warts. However, topical imiquimod cream for warts is restricted by low skin permeability, and several side effects such as itching, pain, and erosions occur most frequently following topical treatment. Microneedle technology, a minimally invasive drug delivery system, has the potential to overcome the barrier of the stratum corneum. This technique would also offer a painless treatment choice and provide personalized therapies. In the study, we loaded imiquimod within dissolving microneedles using the molding method. Gelatin was used as a structural material for microneedle formation without adding a crosslinker. To our knowledge, this is the first study of using dissolving microneedles and exploring their utilization with imiquimod for the treatment of warts. First, we added fluorescent dye and trypan blue into the microneedles to evaluate the status of drugs in the microneedles and the degradation property of microneedles made of gelatin, respectively. Here we also prove the strength of the imiquimod microneedles and study their capability to penetrate the skin. The results show no apparent differences in mechanical failure after an additional imiquimod-loaded. Besides, we provide evidence that imiquimod microneedles induce secreted embryonic alkaline phosphatase (SEAP) in the RAW 264.7 macrophages. Gelatin does not affect the imiquimod in microneedles; a similar immune response was affected by the imiquimod alone or imiquimod complexed with gelatin. Our research demonstrates a proof of concept of using imiquimod microneedles for future warts treatment.

Penile warts are the most common sexually transmitted disease in males. Clinicians should be familiar with the proper evaluation and management of this common condition.

Hippo signalling controls organ growth and cell fate by regulating the activity of the kinase Warts. Multiple Hippo pathway components localize to apical junctions in epithelial cells, but the spatial and functional relationships among components have not been clarified, nor is it known where Warts activation occurs. We report here that Hippo pathway components in Drosophila wing imaginal discs are organized into distinct junctional complexes, including separate distributions for Salvador, Expanded, Warts and Hippo. These complexes are reorganized on Hippo pathway activation, when Warts shifts from associating with its inhibitor Jub to its activator Expanded, and Hippo concentrates at Salvador sites. We identify mechanisms promoting Warts relocalization, and using a phospho-specific antisera and genetic manipulations, identify where Warts activation occurs: at apical junctions where Expanded, Salvador, Hippo and Warts overlap. Our observations define spatial relationships among Hippo signalling components and establish the functional importance of their localization to Warts activation.

Anogenital warts (AGW) can cause economic burden on healthcare systems and are associated with emotional, psychological and physical issues.

Genital warts are benign epithelial tumours caused by human papilloma viruses (HPV), and are sexually transmitted. Genotyping of genital HPV bears great clinical significance in terms of treatment planning, follow-up, and prevention strategies.

Human papillomavirus (HPV) XS2 was isolated from warts on an immunosuppressed patient. After HPV vaccination, the warts resolved. HPVXS2 was also found in warts and normal skin of HIV-positive patients and rarely in HIV-negative controls. Further studies should elucidate the mechanisms that lead to wart clearance.

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.

Mechanical forces have been proposed to modulate organ growth, but a molecular mechanism that links them to growth regulation in vivo has been lacking. We report that increasing tension within the cytoskeleton increases Drosophila wing growth, whereas decreasing cytoskeletal tension decreases wing growth. These changes in growth can be accounted for by changes in the activity of Yorkie, a transcription factor regulated by the Hippo pathway. The influence of myosin activity on Yorkie depends genetically on the Ajuba LIM protein Jub, a negative regulator of Warts within the Hippo pathway. We further show that Jub associates with α-catenin and that its localization to adherens junctions and association with α-catenin are promoted by cytoskeletal tension. Jub recruits Warts to junctions in a tension-dependent manner. Our observations delineate a mechanism that links cytoskeletal tension to regulation of Hippo pathway activity, providing a molecular understanding of how mechanical forces can modulate organ growth.

Epigenetic alteration of host DNA is a common occurrence in both low- and high-risk human papillomavirus (HPV) infection. Although changes in promoter methylation have been widely studied in HPV-associated cancers, they have not been the subject of much investigation in HPV-induced warts, which are a temporary manifestation of HPV infection. The present study sought to examine the differences in promoter methylation between warts and normal skin. To achieve this, DNA was extracted from 24 paired wart and normal skin samples and inputted into the Infinium MethylationEPIC BeadChip microarray. Differential methylation analysis revealed a clear pattern of hyper- and hypomethylation in warts compared to normal skin, and the most differentially methylated promoters were found within the EIF3EP2, CYSLTR1, C10orf99, KRT6B, LAMA4, and H3F3B genes as well as the C9orf30 pseudogene. Moreover, pathway analysis showed that the H3F3A, CDKN1A, and MAPK13 genes were the most common regulators among the most differentially methylated promoters. Since the tissue samples were excised from active warts, however, this differential methylation could either be a cellular response to HPV infection or an HPV-driven process to establish the wart and/or promote disease progression. Conclusively, it is apparent that HPV infection alters the methylation status of certain genes to possibly initiate the formation of a wart and maintain its presence.

To provide an understanding of the changes in sexual function in women with genital warts.

Interferon has been widely used in the treatment of genital warts for its immunomodulatory, antiproliferative and antiviral properties. Currently, no evidence that interferon improves the complete response rate or reduces the recurrence rate of genital warts has been generally provided. The aim of this review is to assess, from randomized control trials (RCTs), the efficacy and safety of interferon in curing genital warts.

Human papillomavirus (HPV) infected keratinocyte dysfunction results in the formation of genital warts, and the specific role of Sonic hedgehog (SHh) signaling in genital warts remains elusive. Thus, this study aimed to identify the correlation between wart formation and SHh signaling.

The human papillomaviruses (HPV) are a group of viruses that, depending on the strain, can cause cancer or the formation of benign growths known as warts. Scarce information exists with regard to the genetic nature of non-genital cutaneous warts induced by the human papillomavirus (HPV).

Low-risk HPV infection has not been the subject of epigenetic investigation. The present study was carried out in order to investigate the methylation status of CpG sites in non-genital cutaneous warts.

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.

Genital warts, which are caused by infection with human papillomavirus (HPV), are one of the most common sexually transmitted diseases in Europe. Although genital warts are commonly perceived as a non-serious condition, treatment is often long, of varying effectiveness and the recurrence rate is high. Very few studies have been performed on the personal consequences of genital warts. The aim of this qualitative study, set in Denmark, was to examine the ways in which genital warts may affect patients' quality of life.

Epithelial cells are the major cell-type for all organs in multicellular organisms. In order to achieve correct organ size, epithelial tissues need mechanisms that limit their proliferation, and protect tissues from damage caused by defective epithelial cells. Recently, the Hippo signaling pathway has emerged as a major mechanism that orchestrates epithelial development. Hippo signaling is required for cells to stop proliferation as in the absence of Hippo signaling tissues continue to proliferate and produce overgrown organs or tumors. Studies in Drosophila have led the way in providing a framework for how Hippo alters the pattern of gene transcription in target cells, leading to changes in cell proliferation, survival, and other behaviors. Scribble (Scrib) belongs to a class of neoplastic tumor suppressor genes that are required to establish apical-basal cell polarity. The disruption of apical-basal polarity leads to uncontrolled cell proliferation of epithelial cells. The interaction of apical basal polarity genes with the Hippo pathway has been an area of intense investigation. Loss of scrib has been known to affect Hippo pathway targets, however, its functions in the Hippo pathway still remain largely unknown. We investigated the interactions of Scrib with the Hippo pathway. We present data suggesting that Drosophila scrib acts downstream of the Fat (Ft) receptor, and requires Hippo signaling for its growth regulatory functions. We show that Ft requires Scrib to interact with Expanded (Ex) and Dachs (D), and for regulating Warts (Wts) levels and stability, thus placing Scrib in the Hippo pathway network.

Infection with the human papillomaviruses (HPV) often involves the epigenetic modification of the host genome. Despite its prevalence among the population, host genome methylation in HPV-induced warts is not clearly understood. In this study, genome-wide methylation profiling was carried out on paired healthy skin and wart samples in order to investigate the effects that benign HPV infection has on gene methylation status. To overcome this gap in knowledge, paired wart (n = 12) and normal skin (n = 12) samples were obtained from Arab males in order to perform DNA extraction and subsequent genome-wide methylation profiling on the Infinium Methylation EPIC Bead Chip microarray. Analysis of differential methylation revealed a clear pattern of discrimination between the wart and normal skin samples. In warts, the most differentially methylated (DM) genes included long non-coding RNAs (AC005884, AL049646.2, AC126121.2, AP001790.1, and AC107959.3), microRNAs (MIR374B, MIR596, MIR1255B1, MIR26B, and MIR196A2),snoRNAs (SNORD114-22, SNORD70, and SNORD114-31), pseudogenes (AC069366.1, RNU4ATAC11P, AC120057.1, NANOGP3, AC106038.2, TPT1P2, SDC4P, PKMP3, and VN2R3P), and protein-coding genes (AREG, GJB2, C12orf71, AC020909.2, S100A8, ZBED2, FABP7, and CYSLTR1). In addition, pathway analysis revealed that, among the most differentially methylated genes, STAT5A, RARA, MEF2D, MAP3K8, and THRA were the common regulators. It can be observed that HPV-induced warts involve a clear and unique epigenetic alteration to the host genome.

Coordination of growth between individual organs and the whole body is essential during development to produce adults with appropriate size and proportions [1, 2]. How local organ-intrinsic signals and nutrient-dependent systemic factors are integrated to generate correctly proportioned organisms under different environmental conditions is poorly understood. In Drosophila, Hippo/Warts signaling functions intrinsically to regulate tissue growth and organ size [3, 4], whereas systemic growth is controlled via antagonistic interactions of the steroid hormone ecdysone and nutrient-dependent insulin/insulin-like growth factor (IGF) (insulin) signaling [2, 5]. The interplay between insulin and ecdysone signaling regulates systemic growth and controls organismal size. Here, we show that Warts (Wts; LATS1/2) signaling regulates systemic growth in Drosophila by activating basal ecdysone production, which negatively regulates body growth. Further, we provide evidence that Wts mediates effects of insulin and the neuropeptide prothoracicotropic hormone (PTTH) on regulation of ecdysone production through Yorkie (Yki; YAP/TAZ) and the microRNA bantam (ban). Thus, Wts couples insulin signaling with ecdysone production to adjust systemic growth in response to nutritional conditions during development. Inhibition of Wts activity in the ecdysone-producing cells non-autonomously slows the growth of the developing imaginal-disc tissues while simultaneously leading to overgrowth of the animal. This indicates that ecdysone, while restricting overall body growth, is limiting for growth of certain organs. Our data show that, in addition to its well-known intrinsic role in restricting organ growth, Wts/Yki/ban signaling also controls growth systemically by regulating ecdysone production, a mechanism that we propose controls growth between tissues and organismal size in response to nutrient availability.