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Borque-Fernando, A. Zapatero, R. Manneh, T. Alonso-Gordoa, F. Couñago, M. Domínguez-Esteban, M. López-Valcárcel, A. Rodríguez-Antolín, N. Sala-González, N. Sanmamed, P. Maroto" "autores" => array:12 [ 0 => array:2 [ "nombre" => "Á." "apellidos" => "Borque-Fernando" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Zapatero" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Manneh" ] 3 => array:2 [ "nombre" => "T." "apellidos" => "Alonso-Gordoa" ] 4 => array:2 [ "nombre" => "F." "apellidos" => "Couñago" ] 5 => array:2 [ "nombre" => "M." "apellidos" => "Domínguez-Esteban" ] 6 => array:2 [ "nombre" => "M." "apellidos" => "López-Valcárcel" ] 7 => array:2 [ "nombre" => "A." "apellidos" => "Rodríguez-Antolín" ] 8 => array:2 [ "nombre" => "N." "apellidos" => "Sala-González" ] 9 => array:2 [ "nombre" => "N." "apellidos" => "Sanmamed" ] 10 => array:2 [ "nombre" => "P." 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A scoping review" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "632" "paginaFinal" => "641" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "H.A. García-Perdomo, V. Granados-Duque, P.E. Spiess" "autores" => array:3 [ 0 => array:4 [ "nombre" => "H.A." "apellidos" => "García-Perdomo" "email" => array:1 [ 0 => "herney.garcia@correounivalle.edu.co" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "V." 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"apellidos" => "Spiess" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "UROGIV Research Group, Universidad del Valle, Cali, Colombia" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Division of Urology/Urooncology, Department of Surgery, School of Medicine, Universidad del Valle, Cali, Colombia" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital Universitario del Valle, Cali, Colombia" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, Estados Unidos" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Department of Genitourinary Oncology and Cancer Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Urology and Oncology, University of South Florida, Tampa, FL, United States" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "¿Cuál es la relación entre el cáncer de pene y el microbioma? Una revisión exploratoria" ] ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0015" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 730 "Ancho" => 1333 "Tamanyo" => 155817 ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The microbiota is defined as the microorganisms in a particular environment. Conversely, the term microbiome is less firmly defined and is used to reference the habitat. Studies of other body systems suggest that the microbiome is critical in maintaining the health and/or development of disease.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Normal tissues tightly regulate growth-promoting and death-inducing signals to maintain homeostatic cell densities, tissue architecture, and function. Dysregulation of these signaling pathways can lead to sustained cellular proliferation. It has also been shown that the host microbiome can be a source of activating signals for aberrant epithelial proliferation as an initiating step in carcinogenesis. It is also associated with multiple diseases arising from the dysregulation of multiple factors, including the microbiota. Gut dysbiosis linked with chronic Clostridium difficile infection and colorectal cancer has been reported. Many other alterations are under investigation.</p><p id="par0015" class="elsevierStylePara elsevierViewall">In this regard, the urinary tract is another focus of interest for finding the relationship between urological diseases and the microbiome. Current studies describe the variant microbe populations in specific disease states or the temporal microbial changes observed throughout a disease. For many conditions, the challenge is to discover whether there is a causal link between microbiome variation and pathology.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The present study aimed to determine the association between the microbiome and penile cancer.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">We performed this scoping review according to the Joanna Briggs Institute's recommendations.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Eligibility criteria</span><p id="par0030" class="elsevierStylePara elsevierViewall">Participants: Theoretical information, <span class="elsevierStyleItalic">in vitro</span> or <span class="elsevierStyleItalic">in vivo</span> studies to know the relationship between penile cancer and the microbiome.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Concept: We evaluated the relationship between the microbiome, its alterations, the oncogenesis, and the possible relationship with penile cancer.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Context: We included all languages.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Information sources</span><p id="par0045" class="elsevierStylePara elsevierViewall">We included studies specific to our objectives to find the relationship between microbiota alterations and the development of penile cancer. A comprehensive literature search followed medical subject headings (MeSh), Emtree language, and related text words. We searched MEDLINE (OVID), Embase, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to now (Appendix 1). We scanned references from relevant articles identified through the search, conferences, thesis databases, Open Grey, Google Scholar, and clinicaltrials.gov, among others, to ensure literature saturation. We contacted the authors by email in case of missing information.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Data collection</span><p id="par0050" class="elsevierStylePara elsevierViewall">Two researchers reviewed each reference by title and abstract. Then, they scanned full texts of relevant studies and applied pre-specified inclusion and exclusion criteria. Disagreements were resolved by consensus. Two trained reviewers, using a standardized form, independently extracted information based on title, objectives, inclusion and exclusion criteria, definitions of outcomes, outcomes, funding source, and other key findings.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Synthesis of results</span><p id="par0055" class="elsevierStylePara elsevierViewall">We descriptively showed the results, pretending to find the relationship between microbiome disturbances and penile cancer. Results were classified under main conceptual categories to facilitate comprehension.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Study selection</span><p id="par0060" class="elsevierStylePara elsevierViewall">We found 2,401 records and 15 studies through other sources. After excluding duplicates and screening by title, abstract, and full text, we finally included nine studies<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–8</span></a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Characteristics of included studies</span><p id="par0065" class="elsevierStylePara elsevierViewall">We included one clinical trial, three retrospective studies, three research articles, and two cases and controls. Also, we enrich our study with review articles that fundamentally addressed the pathogenesis of dysbiosis and penile cancer. The clinical trials and the observational study evaluated the microbiome and the possible factors affecting the penile microbiome. Those studies were conducted in Canada, Kenya, Uganda, the United States of America, the Netherlands, China, and Sweden (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Factors influencing the penile microbiome</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Circumcision</span><p id="par0070" class="elsevierStylePara elsevierViewall">In the 1989 review of the American Academy of Pediatrics Task Force on Circumcision, five major published studies of penile carcinoma in North America were identified. Essentially, all men with penile carcinoma who had not been circumcised neonatally later in life may not offer as much protection against penile carcinoma). Although arguments favor improved hygiene would reduce the risk of penile carcinoma, there is no scientific evidence that this intervention is effective. Further, Liu 2013 reported that changes in microbiota were associated with circumcision. They also found a more significant number of dominant bacterial families, such as Pseudomonadaceae, Clostridiales Family XI, and Prevotellaceae being most commonly dominant, and Fusobacteriaceae, Bifidobacteraciaceae, or Staphylococcaceae in uncircumcised patients.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In contrast, they found pseudomonadaceae, Corynebactericeae, and Staphylococcaceae bacterial families in circumcised patients. After circumcision, predominantly, anaerobic genera decrease substantially, whereas facultative anaerobic genera increase. Also, an aerobic/facultative anaerobic family—Corynebacteriaceae, and a facultative anaerobic family—Staphylococcaceae, are uniquely large post-circumcision coronal sulci samples.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,10,12–14</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Sexual behavior</span><p id="par0080" class="elsevierStylePara elsevierViewall">A diversity of sexually transmitted microbes (STMs) has long been known to have deleterious effects on the health and survival of a range of host taxa. Mounting evidence indicates that the reproductive microbiome can also significantly affect reproductive function. For example, monogamy promotes similarity in the microbiomes of mating partners (i.e., low individual diversity and high differentiation across mating partners). In contrast, polygamy promotes high individual diversity and low differentiation across partners, although this depends on the precise structure of the sexual network. Thereby, male urogenital bacterial studies have focused on sexual preferences, mainly on heterosexual men, where vaginal bacteria such as Lactobacillus, Prevotella, Porphyromonas, Veillonella have been shown in their semen, coronal sulcus, urethral, and urine. Furthermore, bacteria in the semen of men who have sex with other men overlapped with those previously described in the vagina, including Prevotella and Mycoplasma, and Ureaplasma, which have been implicated in male infertility.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,13,15</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Human Papilloma Virus (HPV)</span><p id="par0085" class="elsevierStylePara elsevierViewall">Wakabayashi 2019 described in preclinical studies that changes in microbiota composition can alter local innate immunity. For example, infection with Atopobium vaginae, a prevalent microorganism in bacterial vaginosis, induced changes consistent with a significant disruption of immune barrier properties. Those included increased expression of membrane-associated mucins and robust induction of proinflammatory cytokines (CCL20, IL-1β, IL-6, IL-8, and TNF-α). HPV infections have been causally associated with cancer development, such as cervix, vagina, and vulva in women; penile cancer in men; and cancers of the anus and the head and neck in both women and men. Various studies support the conclusion that HPV affects the local microbiome. It increased microbial diversity with a decreased frequency of Lactobacillus spp. Also, HPV has a 10-fold increase in Bacteroidetes and fusobacteria and a decrease in Actinobacteria. In this way, they indicate that the bacterial microbiota can influence the outcome of HPV infection. Thus, it is plausible that HPV can directly or indirectly induce changes in the infected tissues that affect the local microbiota composition and vice versa. Dysbiosis of the local microbiota may, in turn, create conditions favorable for the colonization and the development of persistent infections with HPV or ultimately promote the development of precancerous lesions. Similarly, dysbiosis of gastric microbiota may promote the development of Helicobacter Pylori-induced gastric malignancies.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17</span></a> In 20–50% of the patients, penile squamous cell carcinoma (SCC) is induced by a persistent infection with high-risk human papillomavirus (hrHPV). The penile cancer microenvironment is highly complex and contains various targets for immunotherapy. Programmed death ligand-1 (PD-L1) expression is a significant predictor for lymph node metastases (LNM) and is associated with worse disease-specific survival (DSS). HPV − penile cancer cells are more often PD-L1 + . This way, hrHPV-mediated is more immunogenic and associated with a better prognosis. Otherwise, HPV-independent is induced by chronic irritation, inflammation, and genetic alterations. Interestingly, the only immune factor that differed from HPV + to HPV − tumors was PD-L1 expression, with higher PD-L1 expression rates in the latter.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11,18–23</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Metabolism disturbances</span><p id="par0090" class="elsevierStylePara elsevierViewall">Bader et al.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> 2020 searched in vitro and metabolic studies strategies and molecular targets of immune metabolism in the tumor microenvironment (TME). Present metabolic changes in immune cells can undermine the effectiveness of the anti-tumor immune response. Also, strategies to alter cell metabolism now offer promising opportunities for cancer therapies (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Lactate</span><p id="par0095" class="elsevierStylePara elsevierViewall">Lactate production can be increased 40-fold in tumor cells, and the lactate-producing enzyme lactate dehydrogenase (LDH) positively correlates with tumor size and clinical severity. Lactate accumulation has direct immunosuppressive effects on immune cells. Lactic acid can inhibit effector T cell function through decreased proliferation and IFN-y production and decrease the pH within the TME to further contribute to immune suppression. Therefore, neutralizing low pH in the TME may have a meaningful impact on improving the efficacy and outcomes of anti-cancer immunotherapy.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Arginine</span><p id="par0100" class="elsevierStylePara elsevierViewall">Arginine is essential in various biological functions, including proliferation, survival, and protein synthesis in cancer and immune cells. Also, CD8 + T cells significantly benefit from L-arginine uptake by enhanced survival, memory formation, and anti-tumor efficacy. Arginine relies on nitric oxide synthetase (NOS) and arginase (ARG) enzyme family activity. Due to its dual roles in both cancer and immune cells, the modulatory effect of arginine within the TME is complicated. Arginine depletion impacts the immune response by increasing myeloid-derived suppressor cell accumulation and inhibiting T-cell function.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Tryptophan</span><p id="par0105" class="elsevierStylePara elsevierViewall">Tryptophan is an essential amino acid that must be taken from the diet to support physiological processes, including cell growth and maintenance. Tryptophan also acts as the substrate for the kynurenine pathway dictated by the rate-limiting enzymes indoleamine-2,3-dioxygenase (IDO1), IDO2, and tryptophan-2,3-dioxygenase (TDO). In cancer, dysregulated IDO1 and TDO activation may suppress anti-tumor immunity. In addition to potential tryptophan depletion, kynurenine can accumulate in IDO-positive cancers and is, in turn, associated with poor prognosis in cancer patients.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p></span></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">Cancer metabolism has been studied extensively through the years. It is widely accepted that oncogenic transformation can cause cancer cells to adapt to a well-characterized metabolic phenotype that can profoundly influence the tumor microenvironment. In addition, the metabolic microenvironment tumors themselves can present an immunosuppressive environment. Consequently, among the associated metabolic alterations, multiple hypotheses have emerged. Some of those alterations in glucose metabolism affect T cell expansion, effector function, and apoptosis; an increase in lactate inhibits T cell function through decreased proliferation and IFN-y production and decreased pH. Also, disturbances on amino acids such as deprivation of glutamine have been found to alter the generation and function of Th1 and Th17 cells; Arginine depletion impacts the immune response through increasing accumulation of myeloid-derived suppressor cells and inhibiting T cell function, and Tryptophan depletion can produce defective interleukin-2 (IL-2) signaling in memory CD4 + T cells.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Infectious agents drive around 20% of cancers, such as HPV, Helicobacter pylori, or hepatitis C virus. In addition, increased levels of specific bacterial and viral species and altered composition of commensal microbiota (dysbiosis) have been detected in several cancer types, such as enrichment of Proteobacteria and Staphylococcus in colorectal and breast cancer, respectively. However, whether changes in the levels of host-microbiota are a cause or result of cancer is still unknown.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The microbiota can be affected by multiple factors, including sexual behavior, sexual preferences, circumcision status, and infections. Whether the composition of the penile microbiota is associated with HPV infection and penile carcinogenesis remains unknown. However, the composition of the penile microbiome was found to be associated with the risk of seroconversion following exposure to infectious microorganisms. Increased abundances of anaerobic bacterial species such as Prevotella, Dialister, Finegoldia, and Peptoniphilus were correlated with an increased risk of HIV seroconversion in uncircumcised men after having contact and being infected with HIV.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8,15</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The different parts of the male reproductive tract constitute a system subdivided by anatomical or physiological barriers. The male reproductive tract consists of an outer part, the penis and the scrotum, and the internal part, the testes, epididymis, accessor glands, vas deferens, and urethra. The microbiota of the male reproductive tract is poorly described. The easily accessible coronal sulcus microbiome showed different bacterial families than the semen, namely Porphyromonadaceae and Prevotellaceae. The results of the male reproductive tract also indicate the presence of a unique microbiome of the different accessible parts.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25–27</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Squamous cell carcinoma is the most common malignancy in penile and vulvar carcinoma, accounting for 90%–95% of cases. There are two main categories of well-studied predisposing factors to penile carcinoma (PC) paralleled in vulvar carcinoma (VC). The first is the HPV-related pathway that is associated with HPV 16, 18, and 33. The second is an HPV unrelated pathway secondary to chronic inflammation, such as lichen sclerosus in VC and balanitis xerotica obliterans in PC.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21,25,28</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Penile cancer is an uncommon malignancy that generally localizes at the penis glans, prepuce, and coronal sulcus. It is frequently originated from the squamous epithelium, as mentioned before. There is a multifactorial etiology associated with poor penile hygiene, smegma retention, phimosis, compromised immune system, smoking, and high-risk HPV infection. Overall, to date, knowledge of the composition of the penile microbiota and its role in penile cancer oncogenesis is minimal. Genomic analysis has revealed a high frequency of TP53 alterations and many other genomic modifications, such as EGFR amplification and alterations in PI3KA and other known oncogenes.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27,29</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Conclusion</span><p id="par0140" class="elsevierStylePara elsevierViewall">Currently, microbiome studies and their relationship with cancer are limited, mainly in the penile microbiome. This finding opens up a field of research. It also encourages the search for new information where future studies explore the relationship between microbiome alteration and cancer of the penis, its mechanisms of action, risk factors, and new therapeutic alternatives can be generated.</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Conflict of interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres2292264" "titulo" => "Graphical abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres2292263" "titulo" => "Abstract" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Evidence Acquisition" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Evidence Synthesis" ] 4 => array:2 [ "identificador" => "abst0030" "titulo" => "Conclusion" ] 5 => array:2 [ "identificador" => "abst0035" "titulo" => "Patient Summary" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1905033" "titulo" => "Keywords" ] 3 => array:3 [ "identificador" => "xres2292262" "titulo" => "Resumen" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "abst0040" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0045" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0050" "titulo" => "Adquisición de la evidencia" ] 3 => array:2 [ "identificador" => "abst0055" "titulo" => "Síntesis de la evidencia" ] 4 => array:2 [ "identificador" => "abst0060" "titulo" => "Conclusión" ] 5 => array:2 [ "identificador" => "abst0065" "titulo" => "Resumen de pacientes" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1905034" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 7 => array:2 [ "identificador" => "sec0015" "titulo" => "Eligibility criteria" ] 8 => array:2 [ "identificador" => "sec0020" "titulo" => "Information sources" ] 9 => array:2 [ "identificador" => "sec0025" "titulo" => "Data collection" ] 10 => array:2 [ "identificador" => "sec0030" "titulo" => "Synthesis of results" ] 11 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Study selection" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Characteristics of included studies" ] 2 => array:3 [ "identificador" => "sec0050" "titulo" => "Factors influencing the penile microbiome" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Circumcision" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Sexual behavior" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "Human Papilloma Virus (HPV)" ] 3 => array:2 [ "identificador" => "sec0070" "titulo" => "Metabolism disturbances" ] 4 => array:2 [ "identificador" => "sec0075" "titulo" => "Lactate" ] 5 => array:2 [ "identificador" => "sec0080" "titulo" => "Arginine" ] 6 => array:2 [ "identificador" => "sec0085" "titulo" => "Tryptophan" ] ] ] ] ] 12 => array:2 [ "identificador" => "sec0090" "titulo" => "Discussion" ] 13 => array:2 [ "identificador" => "sec0095" "titulo" => "Conclusion" ] 14 => array:2 [ "identificador" => "sec0100" "titulo" => "Conflict of interest" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-12-20" "fechaAceptado" => "2024-01-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1905033" "palabras" => array:4 [ 0 => "Penile cancer" 1 => "Microbiome" 2 => "Microbiota" 3 => "Urinary tract" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1905034" "palabras" => array:4 [ 0 => "Cáncer de pene" 1 => "Microbioma" 2 => "Microbiota" 3 => "Tracto urinario" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The microbiota is defined as the microorganisms in a particular environment. Conversely, the term microbiome is less firmly defined and is used to reference the habitat.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Objective</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">To identify the association between the microbiome and the penile cancer</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Evidence Acquisition</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">We performed this scoping review according to the recommendations of the Joanna Briggs Institute. We found five articles that fulfilled the inclusion criteria. We focused on oncogenesis and factors that alter the penile microbiome. We were not limited to language or setting. We searched MEDLINE (Ovid), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and LILACS from inception to the present day.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Evidence Synthesis</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">We found nine studies describing multiple factors that could disturb the microbiome, such as sexual behavior, anatomic alterations including circumcision, and inflammatory factors: lichen sclerosus, poor genital hygiene, compromised immune system, smoking, and HPV infection.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusion</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Overall, knowledge of the composition of the penile microbiota and its role in penile cancer oncogenesis is minimal.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Patient Summary</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Future studies should focus on the relationship between the microbiome and penile cancer to broaden this field of knowledge.</p></span>" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Evidence Acquisition" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Evidence Synthesis" ] 4 => array:2 [ "identificador" => "abst0030" "titulo" => "Conclusion" ] 5 => array:2 [ "identificador" => "abst0035" "titulo" => "Patient Summary" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Introducción</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">La microbiota se define como la comunidad de microorganismos presentes en un entorno concreto. Aunque el microbioma no ha sido claramente definido, el término se utiliza para referirse al hábitat.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Objetivo</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Identificar la relación entre el microbioma y el cáncer de pene.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Adquisición de la evidencia</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Esta revisión exploratoria se realizó siguiendo las recomendaciones del Instituto Joanna Briggs. Se encontraron cinco artículos que cumplían los criterios de inclusión. Nos hemos centrado en investigar la oncogénesis y los factores que alteran el microbioma del pene. No se establecieron limitaciones en cuanto al idioma o la localización. Se realizaron búsquedas en MEDLINE (Ovid), Embase, Registro Cochrane Central de Ensayos Controlados (CENTRAL) y LILACS desde el inicio hasta el momento actual.</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Síntesis de la evidencia</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Se encontraron nueve estudios en los que se describen múltiples factores que pueden alterar el microbioma, como el comportamiento sexual, las alteraciones anatómicas (incluida la circuncisión) y los factores inflamatorios: liquen escleroso, higiene genital deficiente, sistema inmune comprometido, tabaquismo e infección por VPH.</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conclusión</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">En general, hay muy poco conocimiento sobre la composición de la microbiota del pene y su papel en la oncogénesis del cáncer de pene.</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Resumen de pacientes</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Deben realizarse estudios futuros sobre la relación entre el microbioma y el cáncer de pene para ampliar este campo de conocimiento.</p></span>" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "abst0040" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0045" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0050" "titulo" => "Adquisición de la evidencia" ] 3 => array:2 [ "identificador" => "abst0055" "titulo" => "Síntesis de la evidencia" ] 4 => array:2 [ "identificador" => "abst0060" "titulo" => "Conclusión" ] 5 => array:2 [ "identificador" => "abst0065" "titulo" => "Resumen de pacientes" ] ] ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0155" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0110" ] ] ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2069 "Ancho" => 2258 "Tamanyo" => 262118 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Flowchart of included studies.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1861 "Ancho" => 3341 "Tamanyo" => 446487 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Relationship between the microbiome and penile cancer, potential factors are described: (1) Commensal flora, (2) External pathogens, (3) Harmful effects, (4) Risk factors for penile cancer: Smoking, poor hygiene, circumcision, sexual preferences.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study design \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Country \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age range (Years) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Objective \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Population \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Results \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mehta, 2012.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical Trial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kenya \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18−24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">To analyze genital ulcer specimens to identify bacteria potentially associated with Genital Ulcer Disease (GUD) etiology through multitag pyrosequencing of the bacterial small subunit (SSU) ribosomal RNA (rRNA) genes. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2784 Men (uncircumcised, HIV-negative) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39% of the genital ulcer did not have ulcerative sexually transmitted diseases (STI) pathogen recovered. No association with sexual behavior. It is important to understand the mechanism by which circumcision reduces HIV and others STI transmission. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Liu, 2013<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Research Article \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Uganda \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15−49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male circumcision (MC) is hypothesized to reduce HIV risk in men by changing the penile anatomy and by altering the genital microbiology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77 Non-circumcised and 79 Circumcised \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MC significantly reduced the bacterial load by reducing both the prevalence and the absolute abundance of many coronal sulcus bacteria \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Liu, 2014<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Observational study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Canada \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18−65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">To determine how HIV infection and suppressive ART impact the semen microbiome, and whether the semen microbiome might be associated with inflammation and the HIV viral load in semen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 HIV patients and 22 non-HIV patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* Microbiome and bacterial load in HIV infection did not significantly impact semen microbiome, but the restoration of immunity by ART modified the relationship between semen microbiome and CD4 + T-cell count. * Streptococcus was the most common bacterium in semen, irrespective of HIV infection status. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Udager, 2016<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Research Article \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">United States of America \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39−92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">To assess the prevalence and clinicopathologic significance of membranous PD-L1 expression by immunohistochemistry in primary and metastatic penile squamous cell carcinoma. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 aptients expression PDL1+ and 14 patient expression PDL1 - \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Primary tumors in patients with lymph node metastases were significantly more likely to express PD-L1, were associated with decreased cancer-specific survival, more likely to have distant progression, and survival. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">McDaniel, 2015<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Research Article \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">United States of America \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39−92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">To identify driving alterations and potential precision medicine approaches in penile squamous cell carcinoma. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 formalin-fixed, paraffin-embedded tumor samples from 43 cases of penile squamous cell carcinoma. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TP53, CDKN2A, PIK3CA, and HRAS were the most frequently mutated genes. Loss of CDKN2A resulted in a complete inactivation. HPV status and p16 expression were both significantly associated with cancer. p16 expression and HPV + was significantly associated with lack of CDKN2A and TP53 alterations. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ottenhof, 2018<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrospective observational cohort study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Netherlands \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58−74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">To gain insight in the tumor microenvironment (TME), and to identify possible associations between TME factors and lymph node metastases(LNM)/disease-specific survival(DSS) in patients with penile cancer. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">213 patients with penile squamous cell carcinoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The strong prognostic value for hrHPV reflects two tumor entities, one is hrHPV-mediated, more immunogenic, and associated with better prognosis. The other is HPV-independent, induced by chronic irritation, inflammation and genetic alterations. Interestingly, the only immune factor that differed from HPV + to HPV − tumors was PD-L1 expression, with higher PD-L1 expression rates in the latter. Thus hrHPV negativity and diffuse PD-L1 tumor-cell expression were significantly associated with poor disease-specific survival (DSS). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Daling JR, 2005<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Case and control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">United States of America \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18−74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">To compared risk factors of biologic markers of HPV exposure in cases and controls. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">137 cases y 671 controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">There is an increased risk for invasive penile cancer among men not circumcised in childhood and can be attributed to the increased risk associated with phimosis. Phimosis may lead to repeated episodes of inflammation of the glans or foreskin that may predispose to cancer. Also, greater proportion of cases were current smokers and subjects with HPV DNA-negative tumors were more likely to have had phimosis than subjects with HPV-positive tumors. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Brinton LA, 1991<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Case and control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">China \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20−79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">To explore the role of a variety of potential risk factors for penile cancer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">157 cases and 157 controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Early circumcision has been well-documented as a protective factor against the development of penile cancer, but later circumcision which is performed to treat phimosis or certain other penile conditions has been associated with an increased penile-cancer risk. Regarding to smoke, it does not appear to affect the risk of penile cancer. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hellberg D, 1987<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrospective study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sweden \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60−80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">To find the role between penile cancer with smoke and sexual behavior \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">247 cases and 232 controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The association between penile cancer and smoking can be explained biologically (dose-dependent) and is independent of other factors such as phimosis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Harish K, 1995<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Case and control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">India \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No information \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">To determine the role of tobacco in the causation of penile carcinoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">503 Cases and 503 controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any form of tobacco exposure is a risk factor for penile carcinoma (OR = 1.44–3.11). A significant association was noted with a lifetime exposure to > 30 pack years. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3714693.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Characteristics of included studies.</p>" ] ] 3 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 66130 ] ] 4 => array:5 [ "identificador" => "fig0015" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 730 "Ancho" => 1333 "Tamanyo" => 155817 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The microbiome of the urinary tract - A role beyond infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.A. 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