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.

Viral threat to male fertility.

The detrimental effects of Zika virus (ZIKV) infection on mouse testicular functions have reminded a viral threat to male fertility. A broad range of virus families has tropism for male reproductive system, particularly the testes. Certain virus types of these viruses, such as mumps virus and human immunodeficiency virus (HIV), may severely damage the testes and consequently lead to male infertility. ZIKV has been recently found to damage testicular functions and lead to male infertility in mice. Many other viruses also have detrimental effects on host reproduction. Public attention has been paid to sexually transmitted viruses, such as HIV and hepatitis B and C viruses in humans and likewise in economically important farm animals. This article provides an overview on main viruses affecting the male reproductive system and their detrimental effects on fertility, and outlines some important issues for future study.

Ebselen alleviates testicular pathology in mice with Zika virus infection and prevents its sexual transmission.

Despite the low case fatality, Zika virus (ZIKV) infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Antiviral and vaccine developments against ZIKV are still ongoing; therefore, in the meantime, preventing the disease transmission is critical. Primarily transmitted by Aedes species mosquitoes, ZIKV also can be sexually transmitted. We used AG129 mice lacking interferon-α/ß and -γ receptors to study the testicular pathogenesis and sexual transmission of ZIKV. Infection of ZIKV progressively damaged mouse testes, increased testicular oxidative stress as indicated by the levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4, spermatogenesis-associated-18 homolog in sperm and pro-inflammatory cytokines including IL-1ß, IL-6, and G-CSF. We then evaluated the potential role of the antioxidant ebselen (EBS) in alleviating the testicular pathology with ZIKV infection. EBS treatment significantly reduced ZIKV-induced testicular oxidative stress, leucocyte infiltration and production of pro-inflammatory response. Furthermore, it improved testicular pathology and prevented the sexual transmission of ZIKV in a male-to-female mouse sperm transfer model. EBS is currently in clinical trials for various diseases. ZIKV infection could be on the list for potential use of EBS, for alleviating the testicular pathogenesis with ZIKV infection and preventing its sexual transmission.

Pathogenesis and sexual transmission of Spondweni and Zika viruses.

The Spondweni serogroup of viruses (Flaviviridae, Flavivirus) is comprised of Spondweni virus (SPONV) and Zika virus (ZIKV), which are mosquito-borne viruses capable of eliciting human disease. Numerous cases of ZIKV sexual transmission in humans have been documented following the emergence of the Asian genotype in the Americas. The African ZIKV genotype virus was previously implicated in the first reported case of ZIKV sexual transmission. Reports of SPONV infection in humans have been associated with non-specific febrile illness, but no association with sexual transmission has been reported. In order to assess the relative efficiency of sexual transmission of different ZIKV strains and the potential capacity of SPONV to be sexually transmitted, viral loads in the male reproductive tract and in seminal fluids were assessed in interferon α/ß and -γ receptor deficient (AG129) mice. Male mice were inoculated subcutaneously with Asian genotype ZIKV strains PRVABC59 (Puerto Rico, 2015), FSS13025 (Cambodia, 2010), or P6-740 (Malaysia, 1966); African genotype ZIKV strain DakAr41524 (Senegal, 1984); or SPONV strain SAAr94 (South Africa, 1955). Infectious virus was detected in 60-72% of ejaculates collected from AG129 mice inoculated with ZIKV strains. In contrast, only 4% of ejaculates from SPONV-inoculated AG129 males were found to contain infectious virus, despite viral titers in the testes that were comparable to those of ZIKV-inoculated mice. Based on these results, future studies should be undertaken to assess the role of viral genetic determinants and host tropism that dictate the differential sexual transmission potential of ZIKV and SPONV.

Sexually-transmitted seronegative HCV infection in an HIV-positive post-liver transplant recipient. Case report and review of the literature.

We report an HIV-positive patient post liver transplant for non-alcoholic steatohepatitis. Posttransplant liver enzymes became persistently elevated, however HCV antibody was repeatedly negative. Nucleic acid testing subsequently revealed ongoing HCV viremia. Exposure to HCV was on the basis of sexual transmission. The patient was subsequently successfully treated with sofosbuvir/ledipasvir.

Severe acute pharyngotonsillitis due to herpes simplex virus type 2 in a young woman.

Whereas herpes simplex virus type 1 (HSV-1) is a recognized cause of acute oropharyngeal infection in young adults, HSV-2 infections are mostly associated with genital symptoms. We report a case of acute and prolonged febrile ulcerative pharyngotonsillitis with inflammatory syndrome which persisted despite antibiotic therapy for 8 days and required hospitalization in an 18-year old immune competent and sexually active female patient. HSV-2 was evidenced in tonsillar samples and blood by real time PCR, and HSV type-specific serology showed HSV-2 primary infection. Despite delayed diagnosis, acyclovir treatment led to rapid clinical improvement. This case highlights HSV-2 as an unusual cause of pharyngotonsillitis that should be reminded in sexually active patients.

[Analysis of tongue figure features in 990 cases of sexually transmitted and intravenous drug use spread HIV infected population in Xinjiang].

OBJECTIVE: To investigate the tongue manifestation features of sexually transmitted and intravenous drug use spread HIV infected population in Xinjiang. METHODS: Recruited were 990 HIV infected subjects in Xinjiang from May 2011 to March 2012, who were assigned to the intravenous drug use spread HIV infected (498 cases) and the sexually transmitted (492 cases). By using tongue figure shoot combined with analyses of experts, tongue manifestations were analyzed and compared between the sexually transmitted and the intravenous drug use spread from four aspects, i.e., the tongue color, the tongue shape, the fur color, and the fur property. RESULTS: Compared with the sexually transmitted population, red tongue, fissured tongue, yellow fur, thick fur, eroded fur, deficiency of fur fluid were more often seen, showing statistical difference (P < 0.05). Compared with the intravenous drug use spread population, pale tongue, white fur, and thin fur were more often seen, showing statistical difference (P < 0.05). CONCLUSIONS: The tongue manifestations of the intravenous drug use spread HIV population reflected inner exuberance of evil toxin and heat impairing qi and yin. Compared with the intravenous drug use spread population, the attack of HIV infection was more hiding in the sexually transmitted population, with milder internal injury. Their Wei-qi was not damaged and no obvious change occurred in the tongue figure.

Genitoanal human papillomavirus infection and associated neoplasias.

Human papillomavirus (HPV) infection is the most common sexually transmitted virus infection; about 40 out of 150 known HPV genotypes have been associated with genitoanal lesions in the female and male. They have been divided into low-risk (LR) and high-risk (HR) HPV types according to the association of each HPV genotype with genitoanal benign warts, genitoanal cancer and precursor lesions. For the most part, genitoanal HPV infection is equally common in men and in women. Genitoanal HPVs are predominantly transmitted by sexual intercourse. In a minor number of individuals where HR HPV infection has persisted, malignant squamous-cell tumors may develop. There are 15 mucosal oncogenic HPV types which are the etiological factor of cervical cancer and other genitoanal cancers. DNAs of HR HPV types are present in 100% of all cervical carcinomas and in 100% of the precursor lesions, the cervical intraepithelial neoplasias 2 and 3. HPV-16 and -18 alone account for 70% of the oncogenic mucosal HPV types identified. HR HPV types, mostly HPV-16 and -18, are the causes of vaginal and vulvar cancers in females, anal cancers in both genders and cancer of the penis in men. While anal cancers are linked to HR HPVs in more than 80% of cases, only 40% of vulvar cancers and 50% of penile cancers are HPV positive. Genitoanal cancers have a similar anatomy, histology and similar risk factors as well as natural histories. About 60% of vulvar and 50% of penile cancers are HPV negative, but associated with chronic inflammatory disorders, mainly lichen sclerosus. Clinical manifestations of LR HPVs in both sexes are genitoanal warts (condylomata acuminata), which are benign highly infectious tumors. The highest rate of warts is observed in females 16-24 years of age. In males the peak is at the age of 20-24 years. Diagnosis of genitoanal warts should exclude other sexually transmitted infections and diseases. A high number of genitoanal dermatoses, benign tumors, malignant squamous-cell neoplasias and cancer precursors may mimic condylomata acuminata. These malignant counterparts have to be ruled out by biopsy and a thorough histological workup. Therapy of manifest genitoanal HPV-associated lesions has profited from the development of local immunotherapy with imiquimod and local therapy with green tea derivatives (sinecatechin) 10% (Europe) and 15% (USA). Disease recurrence is a crucial problem with treatment, one that could potentially be reduced with the use of immunomodulating agents such as immuquimod and sinecatachins. Recently primary prevention of genitoanal clinical manifestations associated with HPV-6, -11, -16 and -18 including cancer precursors (intraepithelial neoplasias) has become true by the release of prophylactic quadrivalent (HPV-6, -11, -16, -18) and bivalent (HPV-16, -18) vaccines. These vaccines consist of HPV L1 virus-like particles which induce high anti-L1 serum-neutralizing antibody concentrations. Dermatologists and venereologists, general practitioners and pediatricians should cooperate with gynecologists to vaccinate young women and men in order to increase vaccination rates. In Australia and Scotland, an immense efficacy has been observed both regarding the prevention of benign genitoanal warts and cancer precursors caused by the vaccine HPV types. An absolute prerequisite of such a successful prevention against HPV-associated neoplasias is the administration of the vaccine before the first sexual contact.

Human papillomavirus infections of the oral mucosa and upper respiratory tract.

Human papillomaviruses (HPVs) are frequently detected in a variety of lesions in the oral mucosa and upper respiratory tract. The pathogenesis in these areas is not as clearly elucidated as in other anatomical regions, but most experts agree that HPVs are responsible for the commonly observed benign lesions, such as squamous papillomas, verruca vulgaris and recurrent respiratory papillomatosis. Transformation of these benign lesions is well described, but it is not clear what role the virus plays, if any, in carcinogenesis. HPV types 6 and 11 are most frequently detected in oral cavity and respiratory tract lesions, though several other types have also been reported. Despite an opaque understanding of these lesions' pathogeneses, it is essential for the clinician to recognize these diseases, to provide appropriate treatment and to promote patient awareness of potential oral transmission. In this paper, we review the major HPV-associated diseases of the oral mucosa and upper respiratory tract, focusing specifically on clinical features, histopathological characteristics and disease management.

Unexpected high prevalence of HPV 90 infection in an underserved population: is it really a low-risk genotype?

CONTEXT: Human papillomavirus 90 (HPV 90) is a rarely reported genotype worldwide, with few data available to characterize its prevalence, distribution, and disease association. OBJECTIVE: To investigate the prevalence, distribution, and disease association of HPV 90 infection in an underserved inner-city Latino population. DESIGN: Residual SurePath specimens were collected from 808 women referred for abnormal Papanicolaou tests. DNA microarray against HPV subtypes determined HPV genotypes, followed by confirmatory DNA sequencing assays. RESULTS: HPV 90 was detected in 32 women (4%) with an average age of 39 years (range, 23-42 years). Most women (31 of 32) had only HPV 90 infection, and one woman was coinfected with HPV 13. Two women had low-grade intraepithelial lesion and one woman had low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion; the rest of the women had negative concurrent cytology. Available concurrent biopsies in 2 of 3 instances with abnormal cytology confirmed HPV cytopathic effect, with no high-risk HPV detected by in situ hybridization. CONCLUSIONS: We demonstrated an unexpected, high infection rate of HPV 90 in an underserved population in the United States, with 9.4% having concurrent cytologic abnormalities. In the absence of other detectable HPV genotypes by DNA microarray, DNA sequencing, and in situ hybridization, we suspect HPV 90 may be a causative agent responsible for the concurrent cervical lesions. Because of potential shifts in HPV infection patterns in the postvaccine era, monitoring the emergence of previously underrecognized HPV genotypes is becoming increasingly important. To the best of our knowledge, this is the first study to characterize HPV 90 infection in an underserved, North American population.

Virus del papiloma e indicaciones de la vacuna tetravalente / Papillomavirus and indications of tetravalent

El virus del papiloma humano es una de las infecciones de transmisión sexual más comunes, se encuentra asociado con varias enfermedades desde cáncer cervical y anal, hasta verrugas genitales. Sus particulares inmunológicas le permiten subsistir en algunos pacientes y causar enfermedades malignas. Con la aprobación de la vacuna tetravalente contra el VPH los médicos poseemos una nueva arma en la prevención primaria contra el cáncer cervical, las verrugas genitales y el cáncer anal. Este trabajo revisa los conocimientos actuales sobre esta vacuna y sus indicaciones en medicina general.

Modular organizations of novel cetacean papillomaviruses.

The phylogenetic position of cetacean papillomaviruses (PVs: Omikron-PVs and Upsilon-PVs) varies depending on the region of the genome analysed. They cluster together with Alpha-PVs when analysing early genes and with Xi-PVs and Phi-PVs when analysing late genes. We cloned and sequenced the complete genomes of five novel PVs, sampled from genital and oesophageal lesions of free-ranging cetaceans: Delphinus delphis (DdPV1), Lagenorhynchus acutus (TtPV3 variant), and Phocoena phocoena (PphPV1, PphPV2, and PphPV3). Using Maximum Likelihood and Bayesian approaches, all cetacean PVs constituted a monophyletic group with Alpha-, Omega-, and Dyodelta-PVs as inferred from E1-E2 early genes analyses, thus matching the shared phenotype of mucosal tropism. However, cetacean PVs, with the exception of PphPV3, were the closest relatives of Xi-PVs and Phi-PVs in L2-L1 late genes analyses, isolated from cow and goat, thus reflecting the close relationship between Cetacea and Artiodactyla. Our results are compatible with a recombination between ancestral PVs infecting the Cetartiodactyla lineage. Our study supports a complex evolutionary scenario with multiple driving forces for PV diversification, possibly including recombination and also interspecies transmission.

European guideline for the management of hepatitis B and C virus infections, 2010.

These are the guidelines on hepatitis B and C management for IUSTI/WHO in Europe, 2010. They describe the epidemiology, diagnosis, clinical features, treatment and prevention of hepatitis B and C with particular reference to sexual health clinical practice.

Audit of paired anal cytology and histopathology outcomes in patients referred to a public sexual health clinic.

BACKGROUND: The level of agreement between anal cytology and histopathology is not clear with only a few studies evaluating the reliability of anal specimen reporting. Australian data in relation to this are limited. METHODS: The results of paired anal cytology and histopathology specimens received between 2002 and 2008 from patients who were referred within the sexual health clinic were retrieved from the anatomical pathology database. A total of 248 paired samples from 154 (21 females, 133 males) participants were extracted. Concurrent high risk human papilloma virus (hrHPV) DNA assay and HIV status for the study group were also collected. Data were tabulated according to reported grade of squamous abnormality based on the Bethesda system. Using the biopsy result as the gold standard the specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for cytology were calculated and the association between grade of abnormality, HIV status and hrHPV infection estimated. RESULTS: Concordance between cytology and histology showed that in 204 (85%) paired samples both tests were categorised as abnormal (Kappa statistic 0.73, P = 0.013). The cytology result showed a sensitivity of 96%, specificity 14%, PPV 89% and NPV 31% when compared with histopathology. HrHPV assay was positive in 192 (80%) samples. High-grade squamous abnormalities were reported in biopsy specimens from 60% (n = 42/67) of HIV-positive subjects and 25% (n = 22/87) of HIV-negative subjects. HIV-positive individuals were more likely to be hrHPV positive, odds ratio (OR) 6.21 [95% confidence interval (CI) 2.69 to 14.34], when compared with HIV-negative subjects. CONCLUSION: Anal cytology is highly sensitive for the detection of abnormal squamous cells. While cytology has low specificity for predicting the grade of abnormality compared with biopsy outcome, its application as a screening method in asymptomatic at risk populations warrants further study.

Social Networks Shape the Transmission Dynamics of Hepatitis C Virus

Hepatitis C virus (HCV) infects 170 million people worldwide, and is a major public health problem in Brazil, where over 1% of the population may be infected and where multiple viral genotypes co-circulate. Chronically infected individuals are both the source of transmission to others and are at risk for HCV-related diseases, such as liver cancer and cirrhosis. Before the adoption of anti-HCV control measures in blood banks, this virus was mainly transmitted via blood transfusion. Today, needle sharing among injecting drug users is the most common form of HCV transmission. Of particular importance is that HCV prevalence is growing in non-risk groups. Since there is no vaccine against HCV, it is important to determine the factors that control viral transmission in order to develop more efficient control measures. However, despite the health costs associated with HCV, the factors that determine the spread of virus at the epidemiological scale are often poorlyunderstood. Here, we sequenced partial NS5b gene sequences sampled from blood samples collected from 591 patients in São Paulo state, Brazil. We show that different viral genotypes entered São Paulo at different times, grew at different rates, and are associated with different age groups and risk behaviors. In particular, subtype 1b is older and grew more slowly than subtypes 1a and 3a, and is associated with multiple age classes. In contrast, subtypes 1a and 3b are associated with younger people infected more recently, possibly with higher rates of sexual transmission. The transmission dynamics of HCV in São Paulo therefore vary by subtype and are determined by a combination of age, risk exposure and underlying social network. We conclude that social factors may play a key role in determining the rate and pattern of HCV spread, and should influence future intervention policies.

Virus Papiloma Humano (HPV): Parte II - Clínica y terapéutica / Human Papilloma Virus (HPV). Part II – Clinic and therapeutics

Los virus papiloma humano (HPV) pertenecen a la familia de los Papovaviridae y están ampliamente distribuidos en la naturaleza. Se han identificado más de 130 tipos. Pueden comprometer la piel y mucosas provocando lesiones benignas llamadas verrugas. Algunos tipos se asocian con el desarrollo de procesos malignos epiteliales. La respuesta inmune del huésped cumple un rol importante en el control de la infección. El diagnóstico es esencialmente clínico, pero a veces se recurre al estudio histopatológico de las lesiones o al empleo de técnicas de biología molecular. Existe una variedad de opciones terapéuticas, la mayoría destinada a destruir las lesiones. Últimamente se han desarrollado vacunas preventivas para algunos tipos de HPV y se encuentran en experimentación las vacunas terapéuticas.

The human papillomavirus belongs to the family of the Papillomaviridae. This virus is widely distributed in the nature. More than 130 types have been indentifi ed; they can compromise the skin and mucous membranes provoking benign injuries called warts. Some types of virus are said to be involved in the development of precancerous skin lesions. The host immune response has an important role on controlling the infection. The diagnosis is essentially clinic, nevertheless, sometimes histopathologic study of lesions or molecular biology techniques are needed in order to reach an accurate diagnosis. There is a great variety of treatment options; most of them aim to destroy the lesion. Lately some vaccines have been being developed; these are only for some types of HPV and are still under experimental designs (Dermatol Argent 2010;16(2):102-109).