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.

Rab Proteins: Insights into Intracellular Trafficking in Endometrium.

Rab proteins belong to the Ras superfamily of small monomeric GTPases. These G proteins are the main controllers of vesicular transport in every tissue, among them, the endometrium. They are in charge of to the functional subcellular compartmentalization and cargo transport between organelles and the plasma membrane. In turn, intracellular trafficking contributes to endometrial changes during the menstrual cycle, secretion to the uterine fluid, and trophoblast implantation; however, few reports analyze the role of Rab proteins in the uterus. In general, Rab proteins control the release of cytokines, growth factors, enzymes, hormones, cell adhesion molecules, and mucus. Further, the secretion of multiple compounds into the uterine cavity is required for successful implantation. Therefore, alterations in Rab-controlled intracellular transport likely impair secretory processes to the uterine fluid that may correlate with abnormal endometrial development and failed reproductive outcomes. Overall, they could explain recurrent miscarriages, female infertility, and/or assisted reproductive failure. Interestingly, estrogen (E2) and progesterone (P) regulate gene expression of Rab proteins involved in secretory pathways. This review aims to gather information regarding the role of Rab proteins and intracellular trafficking in the endometrium during the different menstrual phases, and in the generation of a receptive stage for embryo implantation, modulated by E2 and P. This knowledge might be useful for the development of novel reproductive therapies that overcome low implantation rates of assisted reproductive procedures.

Prevalence and Genotypes of Human Papillomavirus among Men in Yunnan Province, China.

Human papillomavirus (HPV) infection is one of the most commonly reported sexually transmitted infections. Persistent infection is associated with the development of cervical cancer. Men may serve as a medium for HPV transmission among women, and much remains unknown about the prevalence and genotypes of HPV infection among men in Yunnan Province. This study was designed to investigate these parameters among men in this region. Clinical information was collected from January 2015 to May 2020, and 369 men who wished to undergo tests for HPV were included in this study. HPV screening was performed using the HPV GenoArray Test Kit, and the anatomical site of sample collection was the urethra. The mean age was 36.15 ± 9.08 years. Our results revealed that the prevalence of HPV infection among men was 23.85% in Yunnan Province, and there was no association between age and HPV prevalence in men. There were 72 (81.81%) individuals positive for a single HPV type, and 16 (18.19%) positive for multiple HPV types. The most prevalent oncogenic HPV types were found to be 52, 51, and 16. The most prevalent types of HPV infection were similar between men and women in this region, though the prevalence of HPV in men was relatively high.

Antiviral therapy for the sexually transmitted viruses: recent updates on vaccine development.

INTRODUCTION: The sexually transmitted infections (STIs) caused by viruses including human T cell leukemia virus type-1 (HTLV-1), human immunodeficiency virus-1 (HIV-1), human simplex virus-2 (HSV-2), hepatitis C virus (HCV), hepatitis B virus (HBV), and human papillomavirus (HPV) are major public health issues. These infections can cause cancer or result in long-term health problems. Due to high prevalence of STIs, a safe and effective vaccine is required to overcome these fatal viruses. AREAS COVERED: This review includes a comprehensive overview of the literatures relevant to vaccine development against the sexually transmitted viruses (STVs) using PubMed and Sciencedirect electronic search engines. Herein, we discuss the efforts directed toward development of effective vaccines using different laboratory animal models including mice, guinea pig or non-human primates in preclinical trials, and human in clinical trials with different phases. EXPERT OPINION: There is no effective FDA approved vaccine against the sexually transmitted viruses (STVs) except for HBV and HPV as prophylactic vaccines. Many attempts are underway to develop vaccines against these viruses. There are several approaches for improving prophylactic or therapeutic vaccines such as heterologous prime/boost immunization, delivery system, administration route, adjuvants, etc. In this line, further studies can be helpful for understanding the immunobiology of STVs in human. Moreover, development of more relevant animal models is a worthy goal to induce effective immune responses in humans.

Human papillomavirus is more frequently detected in the pelvic than non-pelvic area in patients with squamous cell carcinoma in situ (Bowen's disease).

BACKGROUND: The detection rate of human papillomavirus (HPV) in Bowen's disease (BD) varies greatly. OBJECTIVES: To detect HPV DNA in BD samples using next-generation sequencing (NGS) and compare HPV detection rates between pelvic and non-pelvic BD. MATERIALS AND METHODS: We evaluated 99 patients with BD in our institution. DNA was extracted from formalin-fixed and paraffin embedded (FFPE) tissue blocks. The presence of HPV DNA material was detected using special kit-based NGS technology. Clinical characteristics and HPV detection rates were then compared between pelvic and non-pelvic BD samples. RESULTS: HPV was detected in 26 (26.3%) BD samples. A total of 10 types of α-HPV was detected: HPV 16, 53, 31, 58, 66, 26, 27, 57, 45, and 72. The most common HPV type was 16 (12.1%). Only two types (27 and 57) were frequently classified as cutaneous type, and the rest were mucosal types. The HPV detection rate was significantly higher in pelvic BD (45.2%) compared to non-pelvic BD (17.6%). CONCLUSION: The present study suggests that sexually transmitted mucosal α-HPV plays a significant role in the pathogenesis of BD, especially in the pelvic region.

Interferon lambda protects the female reproductive tract against Zika virus infection.

Although Zika virus (ZIKV) can be transmitted sexually and cause congenital birth defects, immune control mechanisms in the female reproductive tract (FRT) are not well characterized. Here we show that treatment of primary human vaginal and cervical epithelial cells with interferon (IFN)-α/ß or IFN-λ induces host defense transcriptional signatures and inhibits ZIKV infection. We also assess the effects of IFNs on intravaginal infection of the FRT using ovariectomized mice treated with reproductive hormones. We find that mice receiving estradiol are protected against intravaginal ZIKV infection, independently of IFN-α/ß or IFN-λ signaling. In contrast, mice lacking IFN-λ signaling sustain greater FRT infection when progesterone is administered. Exogenous IFN-λ treatment confers an antiviral effect when mice receive both estradiol and progesterone, but not progesterone alone. Our results identify a hormonal stage-dependent role for IFN-λ in controlling ZIKV infection in the FRT and suggest a path for minimizing sexual transmission of ZIKV in women.

Discriminating high-risk cervical Human Papilloma Virus infections with urinary biomarkers via non-targeted GC-MS-based metabolomics.

Genital human papillomavirus (HPV) is the world's most commonly diagnosed sexually transmitted infection, and high-risk HPV types are strongly linked to cervical dysplasia and carcinoma. Puerto Ricans are among the US citizens with higher HPV prevalence and lower screening rates and access to treatment. This bleak statistic was as a motivation to detect biomarkers for early diagnosis of HPV in this population. We collected both urine and cervical swabs from 43 patients attending San Juan Clinics. Cervical swabs were used for genomic DNA extractions and HPV genotyping with the HPV SPF10-LiPA25 kit, and gas chromatography-mass spectrometry (GC-MS) was employed on the urine-derived products for metabolomics analyses. We aimed at discriminating between patients with different HPV categories: HPV negative (HPV-), HPV positive with simultaneous low and high-risk infections (HPV+B) and HPV positive exclusively high-risk (HPV+H). We found that the metabolome of HPV+B is closer to HPV- than to HPV+H supporting evidence that suggests HPV co-infections may be antagonistic due to viral interference leading to a lower propensity for cervical cancer development. In contrast, metabolites of patients with HPV+H were significantly different from those that were HPV-. We identified three urinary metabolites 5-Oxoprolinate, Erythronic acid and N-Acetylaspartic acid that discriminate HPV+H cases from negative controls. These metabolites are known to be involved in a variety of biochemical processes related to energy and metabolism and may likely be biomarkers for HPV high-risk cervical infection. However, further validation should follow using a larger patient cohort and diverse populations to confirm our finding.

A Population-Based Surveillance Study on the Epidemiology of Hepatitis C in Estonia.

Background and objective: The hepatitis C virus (HCV)-infected patients serve as a reservoir for transmission of the disease to others and are at risk of developing chronic hepatitis C, cirrhosis, and hepatocellular carcinoma. Although the epidemiological data of high rate HCV infection have been obtained in many countries, such data are insufficient in Estonia. Therefore, the aim of the study was to analyze country-specific data on HCV patients. Materials and methods: Data about age, gender, diagnosis, possible risk factors, coinfections, HCV genotypes, liver fibrosis stages and extrahepatic manifestations were collected from 518 patients. Results: The most common risk factors for hepatitis C were injection drug use and tattooing in the 30⁻39 and 40⁻49 year age groups, and blood transfusion in the 50⁻59 and 60⁻69 year age groups. The other risk factors established were profession-related factors and sexual contact. The prevailing viral genotype among the HCV infected patients was genotype 1 (69% of the patients) followed by genotype 3 (25%). Genotypes 1 and 3 correlated with blood transfusions before 1994, drug injections and tattooing. Conclusions: Our study provides the best representation of genotype distribution across Estonia. As a result of the study, valuable data has been collected on hepatitis C patients in Estonia.

Case series on acute HCV in HIV-negative men in regular clinical practice: a call for action.

BACKGROUND: The evidence that HIV treatment as prevention (TasP) and HIV pre-exposure prophylaxis (PrEP) reduces the risk of HIV transmission is overwhelming. But as PrEP and TasP can lead to increased sexual mixing between HIV positive and negative men who have sex with men (MSM), sexually transmitted infections such as acute hepatitis C (HCV), which were thought to be limited to HIV-infected MSM, could become more frequent in HIV uninfected MSM as well. The objective of this study was to describe a series of cases of sexually transmitted HCV infections in HIV-uninfected MSM in the Netherlands and Belgium. METHODS: Through the Dutch Acute HCV in HIV Study (a Dutch-Belgian prospective multicentre study on the treatment of acute HCV infection, NCT02600325) and the Be-PrEP-ared study (a PrEP project in Antwerp, EudraCT2015-000054-37) several acute HCV infections were detected in HIV-negative men. RESULTS: A newly acquired HCV infection was diagnosed in ten HIV-negative MSM. HCV was diagnosed at a sexually transmitted infection (STI) clinic (n = 2), by their general practitioner (n = 2), by their HIV physician (n = 1) or at a PrEP clinic (n = 5). Ten patients reported unprotected anal intercourse and four had a concomitant STI at the time of HCV diagnosis. Six patients reported using drugs during sex. CONCLUSIONS: Our observation calls for a larger nationwide epidemiological study on the prevalence, incidence and risk factors of HCV infection in HIV-uninfected MSM. In the changing landscape of TasP and PrEP, reliable and up-to-date epidemiological data on HCV among HIV-uninfected MSM are needed and will help in developing evidence-based testing policies.

[Correlation between the genotypes and clinical symptoms of human papilloma virus in male outpatients at STD clinics].

OBJECTIVE: To investigate the distribution of the human papilloma virus (HPV) and its genotypes in the male outpatients at the clinics of sexually transmitted diseases (STD) in Changshu and analyze its association with the primary clinical symptoms so as to provide some evidence for the prevention and treatment of HPV infection in men. METHODS: We collected exfoliated cell samples from the external genitals of 602 male outpatients at the STD clinics in Changshu from February 2016 to February 2018, extracted and amplified nucleic acids from the samples, and detected the HPV genotypes using the gene chip technique. We performed statistical analyses on the types of symptoms in clinical diagnosis and their correlation with the genotypes of HPV using the chi-square test. RESULTS: The HPV positive rate in the male STD clinics was 48.2%, of which 47.2 % fell into the low-risk type, 30.0% with multiple infections. The main genotypes included HPV types 6, 11, 39, and 52, and the main HPV-related clinical symptoms were verruca (43.1%) and erythra (41.0%). Low-risk types 6 and 11 accounted for a significantly higher percentage than the high-risk types in the verruca patients (60.0% vs 15.0%, , P < 0.05), but showed no statistically significant difference from the latter in the erythra patients (38.7% vs 38.7%, P > 0.05). The incidence of low-risk infection was remarkably higher than that of high-risk infection in the acrobystitis and balanitis patients (P < 0.05), while the high-risk types constituted a markedly higher percentage than the low-risk and high- and low-risk mixed types in the asymptomatic men at physical examination (84.6% vs 0.0% and 15.4%, P < 0.05). CONCLUSIONS: The HPV positive rate was as high as 48.2% in the males at the STD clinics in Changshu, and the main infection type was low-risk genotype single infection. The clinical symptoms of low-risk infection were mainly verruca and prepuce balanitis, and the high-risk type was mostly asymptomatic at physical examination.

Semen inhibits Zika virus infection of cells and tissues from the anogenital region.

Zika virus (ZIKV) causes severe birth defects and can be transmitted via sexual intercourse. Semen from ZIKV-infected individuals contains high viral loads and may therefore serve as an important vector for virus transmission. Here we analyze the effect of semen on ZIKV infection of cells and tissues derived from the anogenital region. ZIKV replicates in all analyzed cell lines, primary cells, and endometrial or vaginal tissues. However, in the presence of semen, infection by ZIKV and other flaviviruses is potently inhibited. We show that semen prevents ZIKV attachment to target cells, and that an extracellular vesicle preparation from semen is responsible for this anti-ZIKV activity. Our findings suggest that ZIKV transmission is limited by semen. As such, semen appears to serve as a protector against sexual ZIKV transmission, despite the availability of highly susceptible cells in the anogenital tract and high viral loads in this bodily fluid.

Recurrence of Genital Infections With 9 Human Papillomavirus (HPV) Vaccine Types (6, 11, 16, 18, 31, 33, 45, 52, and 58) Among Men in the HPV Infection in Men (HIM) Study.

Background: The purpose of this study was to assess genital recurrence of human papillomavirus (HPV) genotypes included in the 9-valent vaccine and to investigate factors associated with recurrence among men in the HPV Infection in Men (HIM) Study. Methods: Men were followed every 6 months for a median of 3.7 years. HPV genotypes were detected using Roche linear array. Factors associated with type-specific HPV recurrence (infections occurring after a ≥12-month infection-free period) were assessed. Results: In type-specific analyses, 31% of prior prevalent and 20% of prior incident infections recurred. Among prevalent infections, HPV types 52, 45, 16, 58, and 6 and among incident infections, HPV types 58, 52, 18, 16, and 11 had the highest rates of recurrence. New sexual partners (male or female) and frequency of sexual intercourse with female partners were associated with HPV-6, -16, -31, and -58 infection recurrence. In grouped analyses, lifetime and new male sexual partners were associated with recurrence of prior incident infection with any of the 9 HPV types. Conclusions: Recurrence of genital HPV infections is relatively common among men and associated with high-risk sexual behavior. Further studies are needed to understand the role of HPV recurrence in the etiology of HPV-associated diseases.

Human papilloma virus: Apprehending the link with carcinogenesis and unveiling new research avenues (Review).

Human papilloma viruses (HPV) are a small group of non­enveloped viruses belonging to the Papillomaviridae family with strong similarities to polyoma viruses. The viral particles consist of a genome in the form of a circular double­stranded DNA, encompassing eight open reading frames, as well as a non­enveloped icosahedral capsid. HPV infection is considered the most common sexually transmitted disease in both sexes and is strongly implicated in the pathogenesis of different types of cancer. 'High­risk' mucosal HPV types, predominantly types 16, 18, 31, 33 and 35, are associated with most cervical, penile, vulvar, vaginal, anal, oropharyngeal cancers and pre­cancers. Screening for HPV is necessary for the prognosis and for determining treatment strategies for cancer. Novel HPV markers, including proteomic and genomic markers, as well as anti­papillomavirus vaccines are currently available. The aim of this comprehensive review was to thoroughly present the updated information on virus development, cancer occurrence, treatment and prevention strategies, in an attempt to shed further light into the field, including novel research avenues.

Genital human papillomavirus infections.

Human papillomavirus (HPV) infections can have clinical presentations from self-limited benign growth in the skin and mucosal epithelia to malignant growth. HPV infects basal epithelial cells (undifferentiated keratinocytes) of the squamous-columnar junction, especially of the cervix. Although today we understand HPV oncogenesis very well, we have very powerful methods of diagnosis, treatment and prevention of HPV related precancerous lesions, however, more than 270,000 women annually die from cervical cancer worldwide. Integrating HPV vaccination with new, more sensitive, cervical screening assays as part of routine preventive care will improve healthcare for all women. The availability of prophylactic HPV vaccines has provided powerful tools for primary prevention of cervical cancer and other HPV-associated diseases. Secondary prevention through primary high-risk HPV (hr-HPV) testing has the potential to further reduce morbidity and mortality of cervical cancer. However, to achieve the maximum benefit of screening, there is need to continue to identify women who are either unscreened or under-screened. Synergies between HPV vaccination and HPV screening is recommended to improve the effectiveness and cost-effectiveness of prevention HPV-related disease.

Prevalence of Genital Human Papillomavirus Among Sexually Experienced Males and Females Aged 14-59 Years, United States, 2013-2014.

Background: Differences in human papillomavirus (HPV) prevalence among males and females have been reported. Using the 2013-2014 National Health and Nutrition Examination Survey, we evaluated sex differences in prevalence overall and by demographic and sexual behavior characteristics. Methods: Self-collected penile and cervicovaginal swabs from participants aged 14-59 were tested for HPV DNA. Prevalences of any HPV and high-risk HPV (HR-HPV) were estimated for sexually experienced males and females. Overall and in models stratified by demographic characteristics and behaviors, prevalence was compared in males and females using prevalence ratios (PR). Results: Overall, males had higher prevalence than females of any HPV (PR, 1.14; 95% confidence interval [CI], 1.03-1.27) and HR-HPV (PR, 1.24; 95% CI, 1.07-1.43). Prevalences were lower among males than females at ages 14-19 and higher at ages 40-49 and 50-59. Sex differences in models stratified by race/ethnicity, poverty, sexual behaviors, and smoking were observed. After adjusting for lifetime sex partners, most sex differences were attenuated, but males had lower prevalences at ages 14-19 and 20-24 and higher HR-HPV prevalence among non-Hispanic blacks. Conclusions: Any HPV and HR-HPV prevalences were significantly higher in males; sex differences varied by age group and race/ethnicity. Lifetime partners explained many of the differences by sex.

In vitro models for deciphering the mechanisms underlying the sexual transmission of viruses at the mucosal level.

Sexually transmitted viruses infect the genital and colorectal mucosa of the partner exposed to contaminated genital secretions through a wide range of mechanisms, dictated in part by the organization of the mucosa. Because understanding the modes of entry into the organism of viruses transmitted through sexual intercourse is a necessary prerequisite to the design of treatments to block those infections, in vitro modeling of the transmission is essential. The aim of this review is to present the models and methodologies available for the in vitro study of the interactions between viruses and mucosal tissue and for the preclinical evaluation of antiviral compounds, and to point out their advantages and limitations according to the question being studied.

Zika: an ongoing threat to women and infants / Zika: uma ameaça permanente para mulheres e crianças / Zika: una amenaza permanente para mujeres y niños

Recent data from the municipality of Rio de Janeiro, Brazil, shows a sharp drop in the number of reported occurrences of Zika during the summer of 2016/2017, compared to the previous summer. There is still a much higher incidence among women than men, almost certainly due to sexual transmission. An unexpected feature of the new data is that there are proportionally far more cases affecting children under 15 months than older age classes. By comparing incidence rates in 2016/2017 and 2015/2016, we were able to deduce the proportion of reported cases affecting men and women, and verify that gender disparity is still present. Women and children are still risk groups for Zika infection, even during non-epidemic seasons.

Dados recentes do Município de Rio de Janeiro, Brasil, mostram uma queda importante na notificação de casos de Zika no verão de 2016/2017, comparado ao verão anterior. A incidência ainda é muito mais alta em mulheres do que em homens, quase certamente em função da transmissão sexual. Uma característica inesperada dos novos dados é que, proporcionalmente, há muito mais casos em crianças abaixo dos 15 meses de idade, quando comparadas àquelas das faixas mais velhas. Ao comparar as taxas de incidência em 2016/2017 e 2015/2016, conseguimos deduzir a proporção de casos notificados em homens e mulheres e confirmar que a disparidade de gênero ainda existe. As mulheres e crianças ainda são grupos de risco para a infecção pelo vírus Zika, mesmo durante períodos não epidêmicos.

Datos recientes del municipio de Río de Janeiro, Brasil, muestran un descenso importante en la notificación de casos de Zika durante el verano de 2016/2017, comparado con el verano anterior. La incidencia todavía es mucho más alta en mujeres que en hombres, casi con seguridad debido a la transmisión sexual. Una característica inesperada de los nuevos datos es que, proporcionalmente, hay muchos más casos en niños por debajo de los 15 meses de edad, cuando se comparan con aquellas franjas con edad superior. Al comparar las tasas de incidencia en 2016/2017 y 2015/2016, conseguimos deducir la proporción de casos notificados en hombres y mujeres y confirmar que la disparidad de género todavía existe. Las mujeres y niños todavía son grupos de riesgo para la infección por el virus Zika, incluso durante períodos no epidémicos.

The Major Envelope Glycoprotein of Murid Herpesvirus 4 Promotes Sexual Transmission.

Gammaherpesviruses are important human and animal pathogens. Infection control has proven difficult because the key process of transmission is ill understood. Murid herpesvirus 4 (MuHV-4), a gammaherpesvirus of mice, is transmitted sexually. We show that this depends on the major virion envelope glycoprotein gp150. gp150 is redundant for host entry, and in vitro, it regulates rather than promotes cell binding. We show that gp150-deficient MuHV-4 reaches and replicates normally in the female genital tract after nasal infection but is poorly released from vaginal epithelial cells and fails to pass from the female to the male genital tract during sexual contact. Thus, we show that the regulation of virion binding is a key component of spontaneous gammaherpesvirus transmission.IMPORTANCE Gammaherpesviruses are responsible for many important diseases in both animals and humans. Some important aspects of their life cycle are still poorly understood. Key among these is viral transmission. Here we show that the major envelope glycoprotein of murid herpesvirus 4 functions not in entry or dissemination but in virion release to allow sexual transmission to new hosts.

HTLV-1 is predominantly sexually transmitted in Salvador, the city with the highest HTLV-1 prevalence in Brazil.

BACKGROUND: Salvador is the city with the highest number of HTLV-1 infected individuals in Brazil, yet the main route of HTLV-1 transmission is unknown. OBJECTIVE: To investigate the association of syphilis infection as a proxy for sexual transmission of HTLV-1 infection in the general population of this city. METHODS: A cross sectional population-based study was conducted with 3,451 serum samples obtained by a representative simple random sampling. Data on gender, age, income, and years of education were collected by questionnaire and the presence of HTLV, HIV and Treponema pallidum infection was determined by serology. Logistic regression analysis was used to evaluate the independent effect of the potential explanatory variables to HTLV-1 infection and Odds Ratios (OR) and 95% CI were calculated. RESULTS: The majority of studied individuals were female (56.4%), had less than 7 years of education (55.3%) and earned two or less minimum wages (52.0%). The overall prevalence of HTLV-1 was 1.48% (51/3,451; 95% CI: 1.10%- 1.94%), which increased with age. Only three persons younger than 17 (3/958; 0.31%; CI 95% 0.06-0.91) years were infected by HTLV-1. Among the 45 syphilis positives, 12 (26.7%) were HTLV positive, while among 21 HIV positives, only one (4.8%) was HTLV positive. HTLV-1 infection was found to be associated with syphilis infection (ORADJUSTED 36.77; 95% CI 14.96-90.41). CONCLUSION: The data presented herein indicate that horizontal transmission between adults is the main route of HTLV-1 infection in the general population of Salvador and that this is likely to occur through sexual contact.