[Male reproductive health and COVID-19].

The SARS-CoV-2 pandemic has brought serious economic and social problems worldwide'. Due to its medical consequences, it is of importance to study the mechanisms of the disease and new therapeutic interventions, as well as rehabilitation processes. Despite the fact that the genome of the new coronavirus has been sequenced and studied, clinical and epidemiological data are constantly updated and analyzed, and exact pathogenesis has not yet been understood. At the same time, domestic and foreign studies suggest that the virus is an agent that affects not only the lungs, vascular wall, hemostasis, but also the reproductive system. The aim of the review is to summarize the current knowledge about novel SARS-CoV-2, including its pathophysiology and potential impact on male reproductive function.

Prevalence of HPV genital infection in patients with moderate-to-severe psoriasis undergoing systemic treatment with immunosuppressive agents or biologics.

Psoriasis is an immune-mediated inflammatory disease and its relationship with infection has been extensively investigated. Concern for the increased prevalence of human papilloma virus (HPV) infection in patients undergoing systemic immunomodulatory or immunosuppressive therapies for psoriasis has been gradually growing among clinicians. To evaluate the prevalence of HPV in a cohort of patients with psoriasis treated with currently available systemic, conventional and biotechnological drugs. A multi-centric prospective study was conducted in the main dermatological clinical centres of central and southern Italy. Data from 588 patients (366 males and 222 females) with moderate-to-severe psoriasis, aged ≥18 years and treated with conventional and biological drugs, were collected based on a documented history of HPV infection, a positive Papanicolaou test (Pap-test) when available, and clinical evidence of genital warts reported during consultation. Overall, 18 of 588 patients (3.6% [95% CI: 1.8-4.5]) were positive for HPV or had a history of cervical cancer. Considering anamnestic and demographic data, such as gender, age, smoking, weight and body mass index, no statistically significant differences between HPV+ and HPV- patients were found. Moreover, the eradication of HPV infection was successfully achieved using conventional treatments. The prevalence of HPV infection in patients with moderate-to-severe psoriasis, undergoing systemic treatment with immunosuppressive agents or biologics, appears to be the same as that in the general Italian population, indicating that the level of infection among such patients is acceptable.

Genital Human Papillomavirus Prevalence and Genotyping Among Males in Putuo District of Shanghai, China 2015-2019.

BACKGROUND Reports of human papillomavirus (HPV) infection and genotype distribution in Chinese men are limited, and HPV vaccination has not yet been recommended for men in China. MATERIAL AND METHODS We retrospectively reviewed the prevalence and genotyping of male genital HPV. A total of 1227 male patients (aged 17 to 81 years) attending the dermatology and sexually transmitted disease clinics at Putuo District Center Hospital in Shanghai from 2015 to 2019 were included. Genital exfoliated specimens were obtained for detection and genotyping of 27 HPV types by Luminex-based multiplex assay. RESULTS The prevalence of any HPV was 65.5% (804/1227). The rate of multiple infection was 25.8% (317/1227). The 5 main HPV types were 6 (32.0%), 11 (23.2%), 16 (5.6%), 43 (4.3%), and 59 (4.0%). Among all detected HPV genotypes, 65.5% (875/1336) were 9-valent HPV genotypes. No significant differences were observed in the detection rate of HPV infection over 5 years (P>0.05). Age groups ≤24 years (70.7%) and ≥55 years (72.9%) showed higher infection rates, and significant differences were detected in rates of low-risk HPV infection in different age-stratified groups (P<0.05). Prevalence of HPV infection among patients with warts (74.4%) was significantly higher than that of patients with other clinical characteristics (40.4%) and physical examination (63.6%). CONCLUSIONS Our study suggested that more than half of Chinese male patients have detectable HPV infections, and penis-genital and anogenital warts were the most common clinical manifestations. Moreover, the available 9-valent HPV vaccine covers the most frequently observed HPV types among men.

Sequential acquisition of human papillomavirus infection between genital and oral anatomic sites in males.

Oral human papillomavirus (HPV) is associated with increasing rates of HPV-associated oropharyngeal cancer (OPC) in men. Sequential infection from one site to another has been demonstrated at the cervix and anus. Thus, risk of an oral HPV infection after a genital infection of the same type in the HPV infection in men study was investigated. Samples from 3140 men enrolled in a longitudinal cohort were assessed for sequential genital to oral infection with one of nine HPV types (HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58); and then also sequential, same-type oral to genital infection. Incidence rate ratios (IRRs) compared rates of oral HPV among men with and without prior genital infection of the same type. Risk of sequential HPV infections were assessed using Cox proportional hazards model. Incidence of an oral HPV infection was significantly higher among men with a prior genital infection of the same type for any of the 9 HPV types (IRR: 2.3; 95% CI: 1.7-3.0). Hazard ratio of a sequential genital to oral HPV infection was 2.3 (95% CI: 1.7-3.1) and 3.5 (95% CI: 1.9-6.4) for oral to genital infection. Both changed minimally after adjustment for age, country, circumcision, alcohol use, lifetime sexual partners and recent oral sex partners. HPV infections at one site could elevate risk of a subsequent genital or oral HPV infection of the same type in men, emphasizing the importance of vaccination to prevent all HPV infections.

Epizootic reptilian ferlavirus infection in individual and multiple snake colonies with additional evidence of the virus in the male genital tract.

Reptilian ferlavirus, a pathogen of serious concern in snakes, has been reported in Western countries, but little is known about its prevalence in Thailand, where many snake breeding farms are located. In this study, we investigated the reptilian ferlavirus via swab samples derived from 49 diseased snakes and 77 healthy snakes as well as tissue samples taken from nine dead snakes from five independent snake farms. Using molecular detection, we found the ferlavirus in 8.16% of diseased snakes, but not in healthy snakes. Out of nine farmed snakes, eight snakes derived from four farms were found to be positive. Four complete genome sequences of the ferlavirus were successfully obtained and phylogenetically clustered to the highly pathogenic ferlavirus. Tissue tropism of the ferlavirus was identified in various epithelial cell types using the in situ hybridization technique. Interestingly, the hybridization signals were strongly labeled in the male genital tract. Transmission electron microscopy was used to support the ferlaviral localization in the male genital tract. This study provides the first evidence of ferlavirus localization in the male genital tract and contributes to the knowledge about ferlavirus epidemiology, indicating that there needs to be further awareness and elucidation regarding vertical transmission of reptilian ferlavirus.

Genetic variants of HPV-16 and their geographical and anatomical distribution in men: A systematic review with meta-analysis.

BACKGROUND: The prevalence of Human Papillomavirus type 16 (HPV-16) variants in men and the association with tumor development has not been fully investigated. We estimated the prevalence of genital, anal, and oral HPV-16 infections in men through a systematic review and meta-analysis. METHODS: Seven databases were searched and included studies that identified HPV-16 positive males, HPV-16 variants (lineages/sublineages), and indicated the sample's anatomical origin. This protocol is registered in PROSPERO (CRD42020178013). RESULTS: The database searches yielded 14 studies including 445 HPV-16 positive samples classified as lineage A (n = 390), lineage D (n = 43), lineage B (n = 10), and lineage C (n = 2) variants. Lineage A variants predominated among the anatomical sites and the diverse geographical regions. CONCLUSIONS: HPV-16 lineages vary according to anatomical and geographical region. According to this preliminary evaluation of the current literature, we hypothesize that, similar to women, specific HPV-16 variants may also be associated to increased cancer risk in men.

Effect of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on reproductive system.

Since the emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in December 2019, it has rapidly spread across many countries and it has become a crucial global health concern. Furthermore, SARS-CoV-2 infection not only effect on respiratory system, but on reproductive system of human. However, there has been not any review described the transmission paths and effects of SARS-CoV-2 infection on human reproductive system, systematically. In order to describe the transmission paths of SARS-CoV-2, effect on the male/female reproductive system of SARS-CoV-2 and some successful prevention measures. We would like to review effect of SARS-CoV-2 on reproductive system. To conclude, SARS-CoV-2 infection might damage to male reproductive system via ACE2 receptor mediating and male patients were reportedly slightly more affected than women by SARS-CoV-2 infections.

Prevalence of genital HPV infection in STI and healthy populations and risk factors for viral persistence.

Human papillomavirus (HPV) is a well-established carcinogenic agent. This study aimed to assess prevalence and persistence rate of genital HPV infection in sexually transmitted infections (STIs) patients and healthy subjects. The risk factors influencing the persistence of genital HPV infection were also investigated. The samples were collected with the ThinPrep liquid-based cytology system. Among the HPV-positive patients, those consenting were retested after 12 months. Overall, 145/292 subjects proved HPV positive with a higher prevalence (51%) in STI than in healthy population (43%). The persistence of genital HPV infection was statistically associated with female gender, HR-HPV infection, smoking, and Ureaplasma parvum infection.

Burden of genital warts in Colombia: an observational study / Carga das verrugas genitais na Colômbia: um estudo observacional

Introduction: Genital warts are benign lesions caused by sexual transmission of human papillomavirus types 6 and 11, with significant impact on healthcare resource use and patients' quality of life. Objective: To describe the epidemiology of genital warts in adults visiting a physician office for any reason, physician practice patterns, and healthcare resource use and costs in Colombia. Methods: Participants were a convenience sample of 53 physicians in 5 specialties: primary care (15), gynecology (24), urology (12), proctology (1), and dermatology (1). Physicians completed a survey and daily log of all patients 18-60 years old seen over 10 days in their practices in 2016-2017. The physician survey recorded genital warts consultation and management patterns. The daily log recorded patient demographic information and genital warts diagnosis. Results: Among 6,393 patients logged by physicians, the genital warts prevalence was 2.03% (95%CI 1.69­2.38) and incidence 1.30% (95%CI 1.02­1.58). Primary care physicians referred most of their genital warts cases for treatment (female: mean 63.3%, SD=44.8; male: mean 58.3%, SD=43.8). Treatment of non-resistant episodes (<6-month duration) lasted an average of 37.4 days (SD=29.4) and required an average of 4.0 (SD=1.9) office visits for females and 3.0 (SD=1.7) for males. The overall mean cost of an episode of care was USD558.13 (SD=507.30). Conclusion: Genital warts cases reported by most participant physicians were mainly direct-consult, but patients were typically treated by specialists. Much of the genital warts health care utilization and costs reported could be prevented by immunization with the quadrivalent or nonavalent HPV vaccine.

Introdução: As verrugas genitais são lesões benignas, de transmissão sexual, causadas pelo papilomavírus humano tipos 6 e 11 e que causam impacto significativo no uso de recursos de saúde e na qualidade de vida dos pacientes. Objetivo: Descrever a epidemiologia das verrugas genitais em adultos que buscaram atendimento médico ambulatorial por qualquer motivo, incluindo padrões de prática médica, uso de recursos de saúde e custos na Colômbia. Métodos: foi utilizada uma amostra de conveniência composta por 53 médicos em 5 especialidades: clínico geral (15), ginecologia (24), urologia (12), proctologia (1) e dermatologia (1). Os médicos completaram um questionário e registros diários de todos os pacientes com idade entre 18 e 60 anos atendidos durante 10 dias em seus consultórios em 2016-2017. O questionário registrou os padrões de prática médica e de tratamento de verrugas genitais. Os registros diários continham informações demográficas do paciente e o diagnóstico de verrugas genitais. Resultados: Entre 6.393 atendimentos médicos, a prevalência das verrugas genitais foi de 2,03% (IC95% 1,69­2,38) e a incidência de 1,30% (IC95% 1,02­1,58). Os clínicos gerais encaminharam a maioria dos pacientes com verrugas genitais para tratamento (mulheres: média de 63,3%, DP=44,8; homens: média de 58,3%, DP=43,8). O tratamento dos casos não-persistentes (<6 meses de duração) durou em média 37,4 dias (DP=29,4) e requereu uma média de 4,0 (DP=1,9) consultas para mulheres e 3,0 (DP=1,7) para homens. O custo médio geral do tratamento foi de US$ 558,13 (SD=507,30). Conclusão: Os casos de verrugas genitais relatados pela maioria dos médicos participantes derivaram-se principalmente de atendimentos primários e os pacientes foram tratados geralmente por especialistas. Grande parte da utilização de recursos e custos relacionados a verrugas genitais poderia ser evitada pela imunização com a vacina papilomavírus humano 4-valente ou 9-valente.

GLUT1 expression in human papillomavirus-positive anogenital lesions.

BACKGROUND: GLUT1, an ubiquitous glucose transporter in the mammalian cells, is upregulated in many tumours, including human papillomavirus (HPV)-induced head and neck or cervical cancer. OBJECTIVE: To study in anogenital lesions whether or not GLUT1 expression correlates with genomic high-risk HPV integration, the first step in neoplastic transformation. METHODS: Forty-three HPV-positive biopsies positive for either low-risk or high-risk HPV were selected. Paraffin sections adjacent to those tested for the presence of HPV were processed for GLUT1 immunocytochemistry. GLUT1 expression was analysed by two histologists, blinded to HPV type and status and then compared with HPV typing results. RESULTS: Two main staining patterns were observed, either staining from the basal to the granular layer or staining of superficial layers only. The first staining pattern corresponded to lesions with high number of episomal HPV-positive nuclei. Superficial staining was observed in lesions with low number of episomal HPV nuclei or when high-risk HPV was integrated in the cell genome. CONCLUSION: Our results show that GLUT1 overexpression correlates with the number of episomally infected cells in the lesion, but not with the type (low or high risk) of HPV.

Lipschütz genital ulcer revisited: is juvenile gangrenous vasculitis of the scrotum the male counterpart?

Since its first description as ulcus vulvae acutum by Benjamin Lipschütz in 1912, the etiopathogenesis of this peculiar genital ulcer remains incompletely understood. In his original description, two different types of genital ulcers were observed and proposed, which were not precisely defined and distinguished in most subsequent reports. The first type is characterized by acute excruciating genital ulcers of first-time onset with self-limited non-recurrent course in association with gravely symptomatic systemic infections, in which a primary Epstein-Barr virus (EBV) infection is later identified to be probably the most common aetiology. The second type of ulcer usually refers to little painful ulcers of unknown etiopathogenesis in the absence of fever or chills and with a slow torpid progression and recurrent nature. Differentiation from idiopathic aphthous ulcers is unclear. The changes of the cervicovaginal microbiota and microbiome in diseased state deserve further clarification. Acute genital ulcers associated with primary EBV infection in women have drawn attention since 1970s, while the corresponding penile ulcers in men were already known in 1950s. First presented in 1973, juvenile gangrenous vasculitis of the scrotum with an acute painful scrotal ulcer preceded by symptomatic pharyngeal infections can be considered as the male counterpart of ulcus vulvae acutum, and the future clinical survey should include primary EBV infection.

Genital infections due to the human papillomavirus. / Infecciones genitales por el virus del papiloma humano.

The Human Papillomavirus (HPV) is a double-stranded DNA virus, with more than 200 different genotypes having been identified. This infection is considered the most common sexually transmitted infection (STI), and it is the cause of a significant number of diseases, both benign lesions (anogenital condylomas) and pre-malignant lesions and different cancers. The diagnosis of the infection is performed by molecular techniques based on the detection of viral DNA, the mRNA of oncogenic proteins and cellular alteration caused by the infection. Although there is no consensus regarding the best treatment, this should be individualised, and there are different options with ablative treatments being more effective but with greater recurrences, and immunomodulatory treatments being less effective in the short term but with fewer recurrences. Among the preventive strategies, vaccination against HPV is the best strategy against anogenital neoplasms and warts, its maximum effectiveness being when it is administered prior to exposure to HPV.

Human Papillomavirus and Genital Disease in Men: What We Have Learned from the HIM Study.

It is currently recognized that in addition to the major impact of human papillomavirus (HPV) infection in females, HPV causes considerable disease in men at the genitals, anal canal, and oropharynx. Specifically, genital HPV infections may progress to genital warts and penile carcinoma. Although studies concerning the natural history of HPV infections and associated neoplasias have mainly focused on women, during the last 2 decades considerable attention has been given in further understanding these infections in men. The HIM (HPV infection in men) Study, the only prospective multicenter study of male HPV natural history, consisted of a large prospective international cohort study in which men from Brazil, the United States, and Mexico were enrolled. The design and protocols of this study allowed unraveling crucial information regarding the relationship between HPV infection and clinical consequences in men, and associated risk factors at each of the anatomic sites where HPV is known to cause cancer in men.

Persistence and clinical relevance of Zika virus in the male genital tract.

Zika virus (ZIKV) is a re-emerging mosquito-transmitted flavivirus associated with congenital abnormalities in newborns and with Guillain-Barré syndrome in adults. The virus can also be sexually transmitted and can persist in the male genital tract. Studies evaluating the kinetics of ZIKV in seminal shedding of men who have been infected, as well as in animal and cellular models of infection, have shown that, in addition to the testis and epididymis, the prostate and seminal vesicles could also be involved in persistent ZIKV infection. Additionally, some studies have reported that men infected with ZIKV can present with genitourinary symptoms such as haematospermia, prostatitis, painful ejaculation, penile discharge, and oligospermia; however, little is known about the effect of ZIKV on fertility. Understanding the mechanisms that underlie persistent ZIKV infections in men is crucial to developing guidelines, effective vaccines, and therapies.

Trends in the Prevalence of Anogenital Warts Among Patients at Sexually Transmitted Disease Clinics-Sexually Transmitted Disease Surveillance Network, United States, 2010-2016.

BACKGROUND: Approximately 90% of genital warts are caused by human papillomavirus (HPV) types 6 and 11. In the United States, HPV vaccination has been recommended for girls and women aged ≤26 years, and since 2011, for boys and men aged ≤21 years and for gay, bisexual, and other men who have sex with men (MSM) aged ≤26 years. METHODS: Data were obtained from 27 clinics participating in the STD Surveillance Network. Trends in the annual prevalence of anogenital warts (AGW) from 2010-2016 were described by sex and by the sex of sex partners. RESULTS: During 2010-2016, significant declines in the prevalence of AGW were observed in women aged <40 years, men who have sex with women only (MSW) aged <40 years, and MSM of all age categories. An inflection in trend in 2012 was noted for MSW aged 20-24 or 25-29 years and for MSM aged 20-24 years. CONCLUSIONS: The observed declines in the prevalence of AGW suggest that HPV morbidity is declining among populations attending STD clinics, including MSW, MSM, and women. Declines in younger age groups are consistent with what would be expected following the implementation of HPV vaccination. However, declines were also observed in older age groups and are not likely to be the result of vaccination.

Variants in immune-related genes and genital HPV 16 persistence in men.

OBJECTIVES: While most human papillomavirus (HPV) infection clears on its own, persistent HPV infection can cause genital warts and anal, penile and oropharyngeal cancers in men. We conducted genetic analysis in a sub-cohort of the HPV infection in men (HIM) study to test the hypothesis that differences in host genes influence HPV persistence in men. METHODS: Baseline and longitudinal genital HPV status at the genitals was measured every 6-months using the Linear Array assay amplified HPV L1 gene fragment using the PGMY09/11 L1 consensus primer system. DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) in the customized genome-wide genotyping array, the "TxArray," were examined using logistic regression in a case-control study design to assess the association with HPV16 persistence/clearance. RESULTS: Of the total of 737,742 autosomal SNPs in the array, 605,885 passed basic quality control and were examined between 40 men (cases) with > 18 months persistent genital HPV 16 infection vs. 151 controls who were HPV 16-positive, but whose infections cleared in < 18 months. The logistic regression analysis from this case-control study showed variants in several gene regions associated with genital HPV 16 persistence, with the strongest association detected with SNPs on chromosomes 20 (p < 5.72 × 10-6) and 15 (p < 5.89 × 10-6), after adjusting for age, smoking status, number of sex partners and four principal components (ancestral background). CONCLUSIONS: Our results provide a preliminary basis for understanding the biological mechanism of oncogenic HPV 16 pathogenesis at the genitals in men. Some of the genes flanking the top hit SNPs are consistent with previous findings in both HPV related and non-related cancers but further genetic studies in larger cohorts are warranted to confirm these and identify novel major susceptibility genes involved in the pathogenesis of genital HPV persistence in men.

High-risk mucosal HPV types associated with squamous cell carcinoma on the nose tip in an immunocompetent young man

Abstract: The oncogenic role of high-risk HPV in anogenital, head and neck, and cervical cancer is well recognized, but not in skin cancer in the general population. Some authors have demonstrated their appearance mainly on the hands and feet, particularly in the area of the nail bed, which could be due to contamination with HPV types from anogenital regions. Here, we describe a case of genital HPV associated with SCC on the nose tip in an immunocompetent young man, which was confirmed by histopathological findings and in situ hybridization. The importance of this report is to highlight the potential role of HPV in the etiology of skin cancer in an immunocompetent individual.

[HPV infection of the external genitalia in men whose female partners have cervical HPV infection].

OBJECTIVE: Human papilloma virus (HPV) is a necessary cause of cervical cancer and is also closely related to penile cancer, oropharyngeal cancer, and anal cancer in males. However, few studies are reported on male HPV. This study aimed to investigate HPV infection of the external genitalia in men whose female partners have cervical HPV infection. METHODS: We collected the relevant data on the male outpatients whose partners had cervical HPV infection in our Department of Urology and Andrology from August to December 2016. We obtained samples with nylon swabs from the glans penis, corona, inner layer of the prepuce and penile body and detected different types of HPV infection using the Hybribio HPV typing kit, PCR and membrane hybridization. RESULTS: Valid data were collected from 140 males, which showed 83.5% of HPV infection of the external genitalia, including 60 cases of HPV6 (43.2%), 27 cases of HPV16 (19.4%), 14 cases of HPV39 (10.1%), 13 cases of HPV18 (9.4%), 13 cases of HPV58 (9.4%), and 13 cases of HPV52 (9.4%). Redundant prepuce was found in 75.5% of the males, but there was no statistically significant difference in the incidence rate of HPV infection between the normal and redundant prepuce groups (P > 0.05). CONCLUSIONS: Men who have the female partners with positive cervical HPV are at high risk of HPV infection and therefore need to be screened and treated so as to reduce HPV infection in both sexes.

High-risk mucosal HPV types associated with squamous cell carcinoma on the nose tip in an immunocompetent young man.

The oncogenic role of high-risk HPV in anogenital, head and neck, and cervical cancer is well recognized, but not in skin cancer in the general population. Some authors have demonstrated their appearance mainly on the hands and feet, particularly in the area of the nail bed, which could be due to contamination with HPV types from anogenital regions. Here, we describe a case of genital HPV associated with SCC on the nose tip in an immunocompetent young man, which was confirmed by histopathological findings and in situ hybridization. The importance of this report is to highlight the potential role of HPV in the etiology of skin cancer in an immunocompetent individual.