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Concomitant and productive genital infections by HSV-2 and HPV in two young women: A case report.

ABSTRACT: Human papillomaviruses (HPVs), the most oncogenic virus known to humans, are often associated with Herpes Simplex Virus-2 (HSV-2) infections. The involvement of the latter in cervical cancer is controversial but its long-term infections might modulate the mucosal microenvironment in a way that favors carcinogenesis. We know little about coinfections between HSV-2 and HPVs, and studying the immunological and microbiological dynamics in the early stages of these infections may help identify or rule out potential interactions. We report two cases of concomitant productive, although asymptomatic, HSV-2 and HPV infections in young women (aged 20 and 25). The women were followed up for approximately a year, with clinical visits every two months and weekly self-samples. We performed quantitative analyses of their HSV-2 and HPV viral loads, immunological responses (IgG and IgM antibodies and local cytokines expression profiles), vaginal microbiota composition, as well as demographic and behavior data. We detect interactions between virus loads, immune response, and the vaginal microbiota, which improve our understanding of HSV-2 and HPVs' coinfections and calls for further investigation with larger cohorts.

SUBMITTER: Uysal IB

PROVIDER: S-EPMC9478384 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Concomitant and productive genital infections by HSV-2 and HPV in two young women: A case report.

Uysal Ilkay Başak IB Boué Vanina V Murall Carmen Lia CL Graf Christelle C Selinger Christian C Hirtz Christophe C Bernat Claire C Ravel Jacques J Reynes Jacques J Bonneau Marine M Rahmoun Massilva M Segondy Michel M Boulle Nathalie N Grasset Sophie S Groc Soraya S Waterboer Tim T Tribout Vincent V Bravo Ignacio G IG Burrel Sonia S Foulongne Vincent V Alizon Samuel S Tessandier Nicolas N

IDCases 20220819

Human papillomaviruses (HPVs), the most oncogenic virus known to humans, are often associated with Herpes Simplex Virus-2 (HSV-2) infections. The involvement of the latter in cervical cancer is controversial but its long-term infections might modulate the mucosal microenvironment in a way that favors carcinogenesis. We know little about coinfections between HSV-2 and HPVs, and studying the immunological and microbiological dynamics in the early stages of these infections may help identify or rul ...[more]

PMID: 36119756

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Project description:BackgroundGenital human papillomavirus (HPV) is the most common sexually transmitted virus in most populations globally. Adolescent girls and young women (AGYW) remain a key population group at risk for HPV infection. However, the risk factors of HPV infection among AGYW, especially in sub-Saharan Africa, are a subject of little investigation in published literature. Here, we investigated the factors associated with HPV infection among unvaccinated South African AGYW with a high HPV burden (prevalence: 76.1%).MethodsWe retrospectively recruited 213 AGYW learners (aged 15-25 years) from a previous cross-sectional study, the HPV Education Intervention Study, conducted in the Eastern Cape, South Africa. Sexually transmitted infections (STIs), bacterial pathobionts, genital ulcers (due to infectious causes), candidiasis, and bacterial vaginosis (BV) in the self-collected vaginal specimens were determined using the Allplex™ Panel Assays. Statistical analyses were performed using STATA v16.1. Continuous and categorical variables were computed by t-test /Wilcoxon rank-sum test and Chi-square/Fisher's exact tests, respectively. Logistic regression was used to determine the univariable predictors of HPV infection.ResultsThe overall detection rate of any viral STI, bacterial STI, pathobiont, genital ulcer, candidiasis, and BV among the AGYW was 75.0, 34.4, 90.7, 14.4, 26.9, and 43.6%, respectively. The main factors associated with HPV infection were alcohol consumption (p = 0.005), infection with any and multiple Candida species (p = 0.011 and 0.006, respectively), Candida albicans infection (p = 0.010), Ureaplasma urealyticum pathobiont infection (p = 0.044), BV-associated bacteria (specifically Atopobium vaginae: p = 0.039, BV-associated bacteria 2: p = 0.021, Gardnerella vaginalis: p = 0.021, Megasphaera type 1: p = 0.037), and BV (p = 0.011).ConclusionsOur study, albeit not necessarily generalizable, found social behavior as well as specific vaginal microbes as correlates of HPV infection among AGYW in South Africa. There is a need to investigate HPV epidemiology in other AGYW populations. The factors associated with genital HPV infection among AGYW burdened with HPV infection necessitate the need to formulate and implement population-specific public health strategies for creating HPV awareness and reducing its risk.

Project description:Herpes simplex virus (HSV) infections are common and can cause severe illness but no vaccine is currently available. The recent failure of subunit HSV vaccines has highlighted the need for vaccines that present a diverse array of antigens, including the development of next-generation live-attenuated vaccines. However, most attenuated HSV strains propagate poorly, limiting their ability to elicit protective immune responses. A live-attenuated vaccine that replicates in non-neural tissue but is ablated for transmission into the nervous system may elicit protective immune responses without evoking neurologic complications or establishing life-long infections. Initial studies of R2, a live-attenuated vaccine that is engineered to be unable to invade the nervous system, used the guinea pig genital HSV model to evaluate the ability of R2 to replicate at the site of inoculation, cause disease and infect neural tissues. R2 was then evaluated as a vaccine using three routes of inoculation: intramuscular (IM), intradermal (ID) and intravaginal (IVag) and compared to IM administered gD2+MPL/Alum vaccine in the same model. R2 replicated in the genital tract but did not produce acute or recurrent disease and did not infect the neural tissue. The R2 vaccine-induced neutralizing antibody and decreased the severity of acute and recurrent HSV-2 disease as well as recurrent shedding. The ID route was the most effective. ID administered R2 was more effective than gD2+MPL/Alum at inducing neutralizing antibody, suppressing acute disease, and acute vaginal virus replication. R2 was especially more effective at reducing recurrent virus shedding, the most common source of HSV transmission. The live-attenuated prophylactic HSV vaccine, R2, was effective in the guinea pig model of genital HSV-2 especially when administered by the ID route. The use of live-attenuated HSV vaccines that robustly replicate in mucosal tissues but are ablated for neuroinvasion offers a promising approach for HSV vaccines.

Project description:Human papillomavirus (HPV) infections drive one in 20 new cancer cases, exerting a particularly high burden on women. Most anogenital HPV infections are cleared in less than two years, but the underlying mechanisms that favour persistence in around 10% of women remain largely unknown. Notwithstanding, it is precisely this information that is crucial for improving treatment, screening, and vaccination strategies. To understand viral and immune dynamics in non-persisting HPV infections, we set up an observational longitudinal cohort study with frequent on-site visits for biological sample collection. We enrolled 189 women aged from 18 to 25 and living in the area of Montpellier (France) between 2016 and 2020. We performed 974 on-site visits for a total of 1,619 months of follow-up. We collected data on virus load, local immune cell populations, local concentrations of cytokines, and circulating antibody titres. Using hierarchical Bayesian statistical modelling to simultaneously analyse the data from 164 HPV infections from 76 participants, we show that in two months after infection, HPV viral load in non-persisting infections reaches a plateau that lasts on average for 13 to 20 months (95% credibility interval) and is then followed by a rapid clearance phase. This first description of the dynamics of HPV infections comes with the identification of immune correlates associated with infection clearance, especially gamma-delta T cells and CXCL10 concentration. A limitation of this study on HPV kinetics is that many infection follow-ups are censored. Furthermore, some immune cell populations are difficult to label because cervical immunity is less well characterised than systemic immunity. These results open new perspectives for understanding the frontier between acute and chronic infections, and for controlling HPV-associated diseases, as well as for research on human cancers of infectious origin. Trial Registration: This trial was registered is registered at ClinicalTrials.gov under the ID NCT02946346. This study has been approved by the Comité de Protection des Personnes (CPP) Sud Méditerranée I (reference number 2016-A00712-49); by the Comité Consultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Santé (reference number 16.504); by the Commission Nationale Informatique et Libertés (reference number MMS/ABD/ AR1612278, decision number DR-2016-488), by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (reference 20160072000007).

Dataset Information

Concomitant and productive genital infections by HSV-2 and HPV in two young women: A case report.

Publications

Concomitant and productive genital infections by HSV-2 and HPV in two young women: A case report.

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