Characterization and Tissue Tropism of Newly Identified Iflavirus and Negeviruses in Glossina morsitans morsitans Tsetse Flies.

Tsetse flies cause major health and economic problems as they transmit trypanosomes causing sleeping sickness in humans (Human African Trypanosomosis, HAT) and nagana in animals (African Animal Trypanosomosis, AAT). A solution to control the spread of these flies and their associated diseases is the implementation of the Sterile Insect Technique (SIT). For successful application of SIT, it is important to establish and maintain healthy insect colonies and produce flies with competitive fitness. However, mass production of tsetse is threatened by covert virus infections, such as the Glossina pallidipes salivary gland hypertrophy virus (GpSGHV). This virus infection can switch from a covert asymptomatic to an overt symptomatic state and cause the collapse of an entire fly colony. Although the effects of GpSGHV infections can be mitigated, the presence of other covert viruses threaten tsetse mass production. Here we demonstrated the presence of two single-stranded RNA viruses isolated from Glossina morsitans morsitans originating from a colony at the Seibersdorf rearing facility. The genome organization and the phylogenetic analysis based on the RNA-dependent RNA polymerase (RdRp) revealed that the two viruses belong to the genera Iflavirus and Negevirus, respectively. The names proposed for the two viruses are Glossina morsitans morsitans iflavirus (GmmIV) and Glossina morsitans morsitans negevirus (GmmNegeV). The GmmIV genome is 9685 nucleotides long with a poly(A) tail and encodes a single polyprotein processed into structural and non-structural viral proteins. The GmmNegeV genome consists of 8140 nucleotides and contains two major overlapping open reading frames (ORF1 and ORF2). ORF1 encodes the largest protein which includes a methyltransferase domain, a ribosomal RNA methyltransferase domain, a helicase domain and a RdRp domain. In this study, a selective RT-qPCR assay to detect the presence of the negative RNA strand for both GmmIV and GmmNegeV viruses proved that both viruses replicate in G. m. morsitans. We analyzed the tissue tropism of these viruses in G. m. morsitans by RNA-FISH to decipher their mode of transmission. Our results demonstrate that both viruses can be found not only in the host's brain and fat bodies but also in their reproductive organs, and in milk and salivary glands. These findings suggest a potential horizontal viral transmission during feeding and/or a vertically viral transmission from parent to offspring. Although the impact of GmmIV and GmmNegeV in tsetse rearing facilities is still unknown, none of the currently infected tsetse species show any signs of disease from these viruses.

Patterns of Genital Tract Mustelid Gammaherpesvirus 1 (Musghv-1) Reactivation Are Linked to Stressors in European Badgers (Meles Meles).

Gammaherpesvirus reactivation can promote diseases or impair reproduction. Understanding reactivation patterns and associated risks of different stressors is therefore important. Nevertheless, outside the laboratory or captive environment, studies on the effects of stress on gammaherpesvirus reactivation in wild mammals are lacking. Here we used Mustelid gammaherpesvirus 1 (MusGHV-1) infection in European badgers (Meles meles) as a host-pathogen wildlife model to study the effects of a variety of demographic, physiological and environmental stressors on virus shedding in the genital tract. We collected 251 genital swabs from 150 free-ranging individuals across three seasons and screened them for the presence of MusGHV-1 DNA using PCR targeting the DNA polymerase gene. We explored possible links between MusGHV-1 DNA presence and seven variables reflecting stressors, using logistic regression analysis. The results reveal different sets of risk factors between juveniles and adults, likely reflecting primary infection and reactivation. In adults, virus shedding was more likely in badgers in poorer body condition and younger than 5 years or older than 7; while in juveniles, virus shedding is more likely in females and individuals in better body condition. However, living in social groups with more cubs was a risk factor for all badgers. We discuss possible explanations for these risk factors and their links to stress in badgers.

First Report of Phodopus sungorus Papillomavirus Type 1 Infection in Roborovski Hamsters (Phodopus roborovskii).

Papillomaviruses (PVs) are considered highly species-specific with cospeciation as the main driving force in their evolution. However, a recent increase in the available PV genome sequences has revealed inconsistencies in virus-host phylogenies, which could be explained by adaptive radiation, recombination, host-switching events and a broad PV host range. Unfortunately, with a relatively low number of animal PVs characterized, understanding these incongruities remains elusive. To improve knowledge of biology and the spread of animal PV, we collected 60 swabs of the anogenital and head and neck regions from a healthy colony of 30 Roborovski hamsters (Phodopus roborovskii) and detected PVs in 44/60 (73.3%) hamster samples. This is the first report of PV infection in Roborovski hamsters. Moreover, Phodopus sungorus papillomavirus type 1 (PsuPV1), previously characterized in Siberian hamsters (Phodopus sungorus), was the only PV detected in Roborovski hamsters. In addition, after a detailed literature search, review and summary of published evidence and construction of a tanglegram linking the cladograms of PVs and their hosts, our findings were discussed in the context of available knowledge on PVs described in at least two different host species.

Sex differences in the prevalence and determinants of HPV-related external genital lesions in young adults: a national cross-sectional survey in Brazil.

BACKGROUND: External genital lesions (EGL) are the most common sexually transmitted infections (STIs). We aimed to evaluate the prevalence, determinants and sex differences in EGL among young adults from Brazil. METHODS: Overall, 7694 participants (aged 16 to 25 years) underwent an interview, genital examination and sampling for HPV genotyping. RESULTS: The prevalence of EGL was 4.08% (234) and is more frequent in men (5.72%) than women (2.31%) (p <  0.001). Genital lesions were significantly associated with male sex, infection by high-risk and multiple HPV types, having more than two sexual partners in the last year, smoking status and the presence of other STI. While alcohol use was associated with a higher prevalence of EGL in women, same-sex sexual relationship increase the prevalence in men. In the EGL group, 67.79% (p = 0.032) were positive for HPV infection and the types HPV6 and HPV11 were the most prevalent ones. CONCLUSION: The prevalence of EGL in young adults was consistently high, and most cases were associated with genital HPV infection and STIs. Although men have a higher prevalence, both sexes share most genital lesion determinants. The promotion of sexual education and vaccination especially focus in young men, who are usually outside the targets of primary health care programmes, can prevent EGL in Brazilian young adults.

Prevalence and Prognostic Impact of Equus caballus Papillomavirus Type 2 Infection in Equine Squamous Cell Carcinomas in Western Canadian Horses.

Equus caballus papillomavirus type-2 (EcPV-2) has been proposed as a causal factor in equine genital squamous cell carcinoma (SCC). This study had 2 objectives: first, calculate the frequency of papillomavirus (PV) and EcPV-2 infection in papillomas, carcinomas in situ (CIS), and SCCs in Western Canadian horses; and second, determine if EcPV-2 status of equine SCCs is associated with overall survival (OS). EcPV-2 status of 115 archived tissue samples, spanning 6 years, was determined using broad spectrum (MY09/11) and EcPV-2-specific polymerase chain reaction (PCR) assays, EcPV-2-E6/E7 chromogenic RNA in situ hybridization (R-ISH), and amplicon sequencing. A retrospective survey gathered data on history, outcome, breeding, treatment, and rationales of referring veterinarians when managing PV-associated diseases. Histologic grade and completeness of surgical margins of SCCs were also considered. EcPV-2 DNA was identified in 10/58 (17%) SCC, 8/27 (30%) papillomas, 0/5 CIS, and 0/11 lesions identified as "other." Overall, 18/101 (18%) of these lesions were positive for EcPV-2. EcPV-2 was identified in 10/35 (29%) SCCs arising from genital tissues but in 0/22 SCCs from other locations. There was no association between breeding history and EcPV-2 status of genital SCCs. EcPV-2 status of genital SCCs was not associated with OS (P = .76). The strongest negative predictors of OS were a lack of treatment (P < .01) and recurrence post-treatment (P < .01). Weaker predictors of OS included older age at time of diagnosis (P = .02). Completeness of margins at surgical excision, concurrent disease, treatment type, anatomic location of the SCC (anogenital vs other), and histologic grade of the SCC did not influence OS (P > .1).

HSV-2 Infection of Human Genital Epithelial Cells Upregulates TLR9 Expression Through the SP1/JNK Signaling Pathway.

It is known that herpes simplex virus type 2 (HSV-2) triggers the activation of Toll-like receptor (TLR) 9 signaling pathway and the consequent production of antiviral cytokines in dendritic cells. However, the impact of HSV-2 infection on TLR9 expression and signaling in genital epithelial cells, the primary HSV-2 targets, has yet to be determined. In the current study, by using both human genital epithelial cell lines and primary genital epithelial cells as models, we found that HSV-2 infection enhances TLR9 expression at both mRNA and protein levels. Such enhancement is virus replication-dependent and CpG-independent, while the HSV-2-mediated upregulation of TLR9 does not activate TLR9 signaling pathway. Mechanistically, a SP1 binding site on TLR9 promoter appears to be essential for HSV-2-induced TLR9 transactivation. Upon HSV-2 infection, SP1 translocates from the cytoplasm to the nucleus, and consequently binds to TLR9 promoter. By using specific inhibitors, the JNK signaling pathway is shown to be involved in the HSV-2-induced TLR9 transactivation, while HSV-2 infection increases the phosphorylation but not the total level of JNK. In agreement, antagonism of JNK signaling pathway inhibits the HSV-2-induced SP1 nuclear translocation. Taken together, our study demonstrates that HSV-2 infection of human genital epithelial cells promotes TLR9 expression through SP1/JNK signaling pathway. Findings in this study provide insights into HSV-2-host interactions and potential targets for immune intervention.

HIV-1 proteins gp120 and tat induce the epithelial-mesenchymal transition in oral and genital mucosal epithelial cells.

The oral, cervical, and genital mucosa, covered by stratified squamous epithelia with polarized organization and strong tight and adherens junctions, play a critical role in preventing transmission of viral pathogens, including human immunodeficiency virus (HIV). HIV-1 interaction with mucosal epithelial cells may depolarize epithelia and disrupt their tight and adherens junctions; however, the molecular mechanism of HIV-induced epithelial disruption has not been completely understood. We showed that prolonged interaction of cell-free HIV-1 virions, and viral envelope and transactivator proteins gp120 and tat, respectively, with tonsil, cervical, and foreskin epithelial cells induces an epithelial-mesenchymal transition (EMT). EMT is an epigenetic process leading to the disruption of mucosal epithelia and allowing the paracellular spread of viral and other pathogens. Interaction of cell-free virions and gp120 and tat proteins with epithelial cells substantially reduced E-cadherin expression and activated vimentin and N-cadherin expression, which are well-known mesenchymal markers. HIV gp120- and tat-induced EMT was mediated by SMAD2 phosphorylation and activation of transcription factors Slug, Snail, Twist1 and ZEB1. Activation of TGF-ß and MAPK signaling by gp120, tat, and cell-free HIV virions revealed the critical roles of these signaling pathways in EMT induction. gp120- and tat-induced EMT cells were highly migratory via collagen-coated membranes, which is one of the main features of mesenchymal cells. Inhibitors of TGF-ß1 and MAPK signaling reduced HIV-induced EMT, suggesting that inactivation of these signaling pathways may restore the normal barrier function of mucosal epithelia.

Genital self-sampling for HPV-based cervical cancer screening: a qualitative study of preferences and barriers in rural Ethiopia.

BACKGROUND: In the context of WHO's "task shifting" project and growing global consensus on primary HPV-based cervical cancer screening, self-sampling is a promising new tool to expand screening access, uptake and coverage for women worldwide. We aimed to explore perceptions and acceptability of HPV self-sampling-based cervical cancer screening among community members and health professionals in rural northwest Ethiopia and to identify preferences and socio-cultural barriers regarding self-sampling in order to design a suitable high-coverage screening intervention for a rural African setting. METHODS: Four community-based focus group discussions (FGD) were conducted in the rural district of Dabat, Northwest Ethiopia, each comprising 8 to 14 female participants, counting a total of 41 participants. The groups were homogenously composed in terms of their socio-economic status in the community. They included health centre attendees, community members, nurses and health development army leaders (HDAL). Two qualitative data collection experts conducted the interviews in the local language, using a FGD guide with several thematic areas. All participants granted written informed consent prior to the conduct of the interviews. As a concrete example of an existing self-sampling approach for cervical cancer screening we used the Evalyn® Brush. RESULTS: Emerging themes included (i) misconceptions and low awareness about cervical cancer among community residents and primary health care providers in rural northwest Ethiopia, (ii) stigmatization and social exclusion of affected women, (iii) delay in seeking of health care due to poor access and availability of services, and lacking of a concept of early cancer prevention, (iv) need of spousal permission, (v) fear of financial burden and (vi) fear of social marginalization. The self-sampling device was regarded to be acceptable and was judged to be easy to use for most women. The existing Ethiopian health care structure could facilitate a community approach. CONCLUSION: Home-based self-sampling for cervical cancer screening is a socially acceptable and feasible "task shifting" method that will increase cervical cancer screening access and coverage in the Ethiopian study community. Education, awareness creation, community mobilization and family inclusion are identified as key activities to promote, implement and facilitate "task shifting" approaches like self-sampling.

Incidence, Persistence, Clearance, and Correlates of Genital Human Papillomavirus Infection and Anogenital Warts in a Cohort of Men Living With Human Immunodeficiency Virus in South Africa.

OBJECTIVE: To estimate the incidence; persistence and correlates of human papillomavirus (HPV) infection and anogenital warts (AGW) among men living with human immunodeficiency virus (MLHIV). METHODS: Overall, 304 MLHIV 18 years or older were enrolled and attended follow-up visits at 6, 12, and 18 months. Clinicians examined for AGW, collected blood, and penile swabs for HPV testing (Roche Linear Array) at each visit. Time to AGW incidence or clearance was estimated by Kaplan-Meier method. Factors associated with persistent HPV infection and AGW clearance were evaluated with generalized estimating equations and Cox regression, respectively. RESULTS: Mean age of participants was 38 years (standard deviation, 8 years); 25% reported more than 1 sexual partner in the past 3 months. Most (65%) participants were on antiretroviral treatment (ART) with a median CD4 count of 445 cells/µL (interquartile range, 328-567). Prevalence of HPV infection and AGW at enrolment were 79% (224 of 283) and 12% (36 of 304), respectively. Two hundred fifty-nine men were followed up for a median (interquartile range) 1.4 years (0.5-1.7 years). Incidence of any-genital HPV infection was 2.9 (95% confidence interval, 1.5-5.5) per 100 person-years. Persistence of any-genital HPV infection was 35% (68 of 192) and was higher among MLHIV with low CD4 count (adjusted odds ratio, 3.54; 95% confidence interval, 2.07-6.05). Incidence of AGW was 1.4 per 100 person-years. Men living with human immunodeficiency virus with high CD4 count were more likely to clear AGW than those with low CD4 count (adjusted hazard ratio, 3.69; 95% confidence interval, 1.44-9.47). No associations were observed between persistent genital HPV infection, AGW clearance with enrolment ART status or duration. CONCLUSIONS: Human immunodeficiency virus-positive men have a high burden of genital HPV infection and AGW. The ART and HPV vaccine could reduce this burden.

Hand-to-genital and genital-to-genital transmission of human papillomaviruses between male and female sexual partners (HITCH): a prospective cohort study.

BACKGROUND: Hand-to-genital contact is hypothesised to be a transmission mode of human papillomavirus (HPV) of the Alphapapillomavirus genus. We compared the relative importance of hand-to-genital and genital-to-genital HPV transmission between sexual partners. METHODS: In this prospective cohort study, we recruited and followed up female university students aged 18-24 years and their male sexual partners in Montreal, QC, Canada (2005-11). Participants were eligible if they had initiated sexual activity within the past 6 months. Women were examined at clinic visits at baseline and every 4-6 months for up to 24 months. Men had a baseline visit and a single follow-up visit approximately 4 months later. Partners provided hand and genital swab samples, which we tested for DNA of 36 HPV types using PCR. We assessed predictors of incident type-specific HPV detections using Cox proportional hazards models. FINDINGS: Participants were recruited between June 5, 2006, and April 4, 2013. 264 women and 291 men had valid hand samples. The hazard ratio (HR) of incident detection of HPV in genital samples from women was 5·0 (95% CI 1·5-16·4) when her partner was positive for the same HPV type on his hand versus negative, but adjustment for his genital HPV status reduced the HR to 0·5 (0·1-1·8). Similarly, the HR of incident detection of HPV on men's genitals was 17·4 (95% CI 7·9-38·5) when his partner was positive for the same HPV type on her hand versus negative, but adjustment for her genital HPV status reduced the HR to 2·3 (0·9-6·2). Conversely, the HR of type-specific incident detection of HPV in genital samples associated with partner genital HPV positivity was 19·3 (95% CI 11·8-31·8) for women and 28·4 (15·4-52·1) for men after adjustment for their hand HPV status. INTERPRETATION: Clinicians can reassure their patients that HPV transmission is unlikely to occur through hand-to-genital contact. The majority of genital HPV infections are likely to be caused by genital-to-genital sexual transmission. FUNDING: Canadian Institutes for Health Research, National Institutes of Health, Fonds de la Recherche en Santé du Québec, and Merck & Co.

The relationship between anogenital HPV types and incident HIV infection among men who have sex with men and transgender women in Lima, Peru: Findings from a prospective cohort study.

Although it is known that individuals living with HIV have a higher HPV prevalence, the impact of individual HPV types on HIV acquisition is less clear. In this prospective cohort study we investigated the relationship between HPV types and incident HIV infection among men who have sex with men (MSM) and transgender women (TW) in Lima, Peru. Six hundred HIV-negative Peruvian MSM and TW participated in a 2-year study with biannual visits. At baseline, participants completed a computerized, self-administered questionnaire on sexual behavior and HPV knowledge and underwent a physical exam including anogenital swabs for HPV DNA (37 genotypes via linear array testing) and HIV testing; follow-up visits included the questionnaire and HIV testing. Participant mean age was 25 years (range = 18-40), with 48.9% self-identifying as gay and 86.5% reporting having sex exclusively with men. At baseline, 530 participants had HPV DNA present (61.1% with high-risk HPV, 84.9% with low-risk HPV). Among 571 participants who returned for any study visit, 73 (12.8%) became infected with HIV during the 2-year follow-up (6% HIV incidence). Compared to those without HIV, more participants with HIV had any HPV type present (97.3% vs. 87.6%, respectively, p = .01), more than one HPV type (79.5% vs. 58.2%, p < .01), or high-risk HPV (72.6% vs. 51.4%, p < .01). Some participants lost to follow-up could have been HIV-positive, which would have affected the relationship of HPV and HIV infection. Our prospective study showed that participants with any HPV type, more than one HPV type, or high-risk HPV were more likely to test positive for HIV. Although most studies have shown HPV-HIV coinfection, our findings illustrate the strong relationship between individual HPV types and HIV infection. This further illustrates the potential utility of HPV vaccine for MSM and TW, not only for HPV prevention but also possibly for HIV prevention.

Association between Human Papillomavirus and Non-cervical Genital Cancers in Brazil: A Systematic Review and Meta-Analysis

Background: Human papillomavirus (HPV) infection is associated with cervical cancer; however, it is controversial whether it is involved in non-cervical genital cancers. Objective: This study aimed to evaluate articles on the prevalence of HPV in penile cancer, vulvar cancer, colorectal cancer, prostate cancer and anal canal cancer in studies conducted in Brazil. Methods: The study was conducted in accordance with the Preferred Reporting of Systematic Reviews and Meta-Analysis Statement. Comprehensive searches for HPV and cancer for the years 2006 to 2016 were conducted in two databases (PubMed and Web of Knowledge) and Google Scholar system. We also tracked the references of all eligible articles to identify additional non-captured publications through online surveys. Results: Eighteen studies, with a combined sample size of 1,552 patients were analyzed. The overall prevalence of HPV was 43% (95% CI: 36­51%; p < 0.001). The pooled prevalence of HPV in penile cancer was 42% (95% CI: 32­55%; p < 0.001), in colorectal cancer it was 67% (95% CI: 64­70%; p < 0.001) and in vulvar cancer 43% (95% CI: 34­55%; p < 0.001). HPV 16 was the most prevalent in all sites evaluated, with prevalence estimated at 54% (95% CI: 44­66%; p < 0.001), followed by genotypes 33 (21%; 95% CI: 17­28; p < 0.001), 6 (15%; 95% CI: 8­26%; p < 0.001), 11 (13%; 95% CI: 5­32%; p < 0.001) and 18 (12%; 95% CI: 7­22%; p < 0.001), respectively. The pooled prevalence of single infection was 82% and infection by multiple genotypes of HPV was 22%. Conclusion: Our study demonstrated a high prevalence of HPV in non-cervical genital cancers in Brazil, with predominance of genotype 16, providing evidence for the need for preventive and control measures to avoid future harm to the population.

Trends in the relative prevalence of genital ulcer disease pathogens and association with HIV infection in Johannesburg, South Africa, 2007-2015.

BACKGROUND: In South Africa, treatment of genital ulcer disease (GUD) occurs in the context of syndromic management. GUD aetiological studies have been conducted in Johannesburg since 2007. We report on GUD pathogen prevalence, sero-prevalence of STI co-infections and aetiological trends among GUD patients presenting to a community-based primary healthcare facility in Johannesburg over a 9-year period. METHODS AND FINDINGS: GUD surveys were conducted from January to April each year. Consecutive genital ulcers were sampled from consenting adults. Swab-extracted DNA was tested by multiplex real-time PCR assays for herpes simplex virus (HSV), Treponema pallidum (TP), Haemophilus ducreyi (HD) and Chlamydia trachomatis (CT). HSV-positive DNA extracts were further subtyped into HSV-1 and HSV-2 using a commercial PCR assay; CT-positive extracts were tested with an in-house PCR assay specific for serovars L1-L3 (lymphogranuloma venereum). Sera were tested for HIV, HSV-2, and syphilis co-infections. Giemsa-stained ulcer smears were screened for Klebsiella granulomatis by microscopy. Data were analysed with STATATM version 14. Of 771 GUD specimens, 503 (65.2%) had a detectable pathogen: HSV 468 (60.7%); TP 30 (3.9%); CT L1-3 7 (0.9%); HD 4 (0.5%). No aetiological agents were detected in 270 (34.8%) ulcer specimens. Seroprevalence rates were as follows: HIV 61.7%; HSV-2 80.2% and syphilis 5.8%. There was a strong association between GUD pathogen detection and HIV seropositivity (p < 0.001); 68% of cases caused by HSV were co-infected with HIV. There was a significant decline in the relative prevalence of ulcer-derived HSV over time, predominantly from 2013-2015 (p-value for trend = 0.023); and a trend towards a decrease in the HIV seropositivity rate (p-value for trend = 0.209). CONCLUSIONS: HSV remains the leading cause of pathogen-detectable GUD in South Africa. The prevalence of HIV co-infection among GUD patients is high, underlining the importance of linkage to universal HIV testing and treatment in primary healthcare settings.

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.

Breast Milk Is a Potential Vehicle for Human Papillomavirus Transmission to Oral Mucosa of the Spouse.

BACKGROUND: Human papillomavirus (HPV) DNA has been detected in breast milk, but its origin has remained obscure. The aim of the study was to analyze the prevalence and persistence of HPV in breast milk in the Finnish Family HPV cohort study. The association of breast milk HPV positivity with the family members' oral HPV status was evaluated. METHODS: We included 308 families to the study where the mother was breast feeding her offspring. Mothers collected the milk samples manually at day 3, and at months 2, 6 and 12. Cervical and/or oral samples were collected from all family members. HPV testing was performed using nested polymerase chain reaction and Luminex-based Multimetrix kit. RESULTS: Breast milk HPV DNA was found in 10.1% (31/308), 20.1% (39/194) and 28.8% (17/59) of samples at day 3, months 2 and 6, respectively. The following HPV genotypes were detected: 6, 16, 18, 33, 45, 53, 56, 59, 66 and 82. Breast milk HPV persisted among 5.5% (9/164) of the lactating mothers. No significant associations were detected between the persistent breast milk HPV and the offspring's oral incident HPV infection. Breast milk HPV positivity showed a strong association with the fathers' oral HPV positivity at baseline, as well as at 6- and 12-month follow-up visits, with odds ratio (OR) = 3.24 [95% confidence interval (CI): 1.04-10.12], OR = 6.34 (95% CI: 1.84-21.89) and OR = 14.25 (95% CI: 1.16-174.80), respectively. CONCLUSIONS: HPV in breast milk is prevalent among the lactating mothers and HPV can also persist in breast milk. The breast milk is a potential vehicle for HPV transmission to oral mucosa of the spouse but not of the offspring.

Variation in genital human papillomavirus infection prevalence and vaccination coverage among men and women in the USA.

Human papillomavirus (HPV) is the most common sexually transmitted infection that causes majority of anogenital and oropharyngeal cancers. Prophylactic HPV vaccine is available for the primary prevention of cancer and HPV transmission. Here, we are going to discuss the variation of HPV prevalence, HPV vaccination coverage and potential risk factors of men and women, retrieved from the cross-sectional study of the National Health Nutrition Examination Survey, a representative sample of noninstitutionalized, civilian residents in the USA. The overall penile HPV prevalence in men was 45.2% and the high risk oncogenic HPV prevalence defined by DNA testing was 25.1% that appeared to be widespread among all the age groups, which contrasts the vaginal HPV prevalence of 26.8% in women.

In Situ Detection of Regulatory T Cells in Human Genital Herpes Simplex Virus Type 2 (HSV-2) Reactivation and Their Influence on Spontaneous HSV-2 Reactivation.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) reactivation is accompanied by a sustained influx of CD4(+) and CD8(+) T cells that persist in genital tissue for extended periods. While CD4(+) T cells have long been recognized as being present in herpetic ulcerations, their role in subclinical reactivation and persistence is less well known, especially the role of CD4(+) regulatory T cells (Tregs). METHODS: We characterized the Treg (CD4(+)Foxp3(+)) population during human HSV-2 reactivation in situ in sequential genital skin biopsy specimens obtained from HSV-2-seropositive subjects at the time of lesion onset up to 8 weeks after healing. RESULTS: High numbers of Tregs infiltrated to the site of viral reactivation and persisted in proximity to conventional CD4(+) T cells (Tconvs) and CD8(+) T cells. Treg density peaked during the lesion stage of the reactivation. The number of Tregs from all time points (lesion, healed, 2 weeks after healing, 4 weeks after healing, and 8 weeks after healing) was significantly higher than in control biopsy specimens from unaffected skin. There was a direct correlation between HSV-2 titer and Treg density. CONCLUSIONS: The association of a high Treg to Tconv ratio with high viral shedding suggests that the balance between regulatory and effector T cells influences human HSV-2 disease.

Genotype-specific concordance of oral and genital human papillomavirus infections among marital couples is low.

Data on genotype-specific concordance of oral-oral and genital-oral HPV infections among marital couples are key to understand HPV transmission between spouses. Genotype-specific concordance of HPV infections (oral/genital) and their co-variates among 131 marital couples were determined during 6-year follow-up (FU). Seven oral scrapings were taken from both spouses, accompanied by six genital samplings from the women and one (at baseline) from the male partners. HPV-genotyping was performed by nested PCR and a Luminex®-based Multimetrix Assay. Demographic data were collected with questionnaires at baseline and study conclusion. Prevalence of oral HPV varied from 10.3 to 27.0 % and 15.8 to 31.3 % in women and men, respectively. At baseline, 37.6 % of the male genital samples were HPV-positive while in female genital samples, HPV prevalence varied from 13.3 to 59.4 %. Only 15 couples had HPV genotype-specific concordance (oral-oral n = 7; male oral-female genital n = 9; female oral-male genital n = 2). In the nested case-control setting, higher number of deliveries (OR 0.145, 95%CI 0.030-0.706, p = 0.017) and higher number of intercourse (OR 0.488, 95%CI 0.243-0.978, p = 0.043) decreased the likelihood of concordant HPV infections while practicing oral sex increased the risk (OR 0.299, 95%CI 0.120-0.748, p = 0.010). In multivariate analysis, the likelihood of concordance was decreased by higher number of pregnancies of the female partner (p = 0.020) and by higher frequency of intercourse reported by the male spouse (p = 0.027). To conclude, asymptomatic HPV infections were common in both spouses while genotype-specific concordance was low. This supports the view that HPV profile of the spouses has been established before the current marital relationship.

[Combined treatment of genital human papillomavirus infection in men].

This study aimed to assess the efficacy of treatment of genital human papillomavirus infection in 107 men. Patients in group 1 (n=51) underwent laser ablation of genital warts, patients in group 2 (n=56) were treated with laser ablation in conjunction with the administration of an immune system medication izoprinozin. During the first 9 months post-treatment, human papillomavirus infection relapse rate in group 1 was 23,5% and in group 2 - 5,4%. It was likewise observed that the combined treatment of genital warts resulted in reduced incidence of infective complications and the time of wound epithelialization after laser papilloma ablation.