Background:The composition of the vaginal microbiota is known to be highly structured into five main community state types (CSTs) that are found in all human populations. Several associations between perceived ethnicity and the type of community have been reported but analyses of human genetic data, especially genome wide association studies (GWAS), remain limited and mostly rely on phenotypic traits rather than microbial DNA data. Methods:Analysing genotyping data from in 168 women from the PAPCLEAR cohort study in France, we perform a GWAS looking for human genetic polymorphisms associated with vaginal microbiota community composition. For the latter, we use Simpson diversity and community state type (CST) as summary statistics to summarise 16S RNA metabarcoding data. Results:We show that inverse Simpson diversity is the trait related to the vaginal microbiota that is best explained by the human genome. Furthermore, we identify several genomic regions associated with variations in this trait and show that the covariates associated with vaginal microbiota composition do not correlate with these genetic variants. Conclusion:This is one of the first GWAS to use microbial genetic data instead of symptoms to characterise the vaginal microbiota. However, it remains limited because of the size of our cohort and our results call for more powered studies in terms of participants and genome coverage.

Background The composition of the vaginal microbiota is known to be highly structured into five main community state types (CSTs) that are found in all human populations. Several associations between perceived ethnicity and the type of community have been reported but analyses of human genetic data, especially genome wide association studies (GWAS), remain limited and mostly rely on phenotypic traits rather than microbial DNA data. Methods Analysing genotyping data from in 168 women from the PAPCLEAR cohort study in France, we perform a GWAS looking for human genetic polymorphisms associated with vaginal microbiota community composition. For the latter, we use Simpson diversity and community state type (CST) as summary statistics to summarise 16S RNA metabarcoding data. Results We show that inverse Simpson diversity is the trait related to the vaginal microbiota that is best explained by the human genome. Furthermore, we identify several genomic regions associated with variations in this trait and show that the covariates associated with vaginal microbiota composition do not correlate with these genetic variants. Conclusion This is one of the first GWAS to use microbial genetic data instead of symptoms to characterise the vaginal microbiota. However, it remains limited because of the size of our cohort and our results call for more powered studies in terms of participants and genome coverage.

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).

The vaginal microbiota is known to affect women's health. Yet, there is a notable paucity of high-resolution follow-up studies lasting several months, which would be required to interrogate the long-term dynamics and associations with demographic and behavioural covariates. Here, we present a high-resolution longitudinal cohort study of 125 women, followed for a median duration of 8.6 months, with a median of 11 samples collected per woman. Using a hierarchical Bayesian Markov model, we characterised the patterns of vaginal microbiota community persistence and transition, simultaneously estimated the impact of 16 covariates and quantified individual variability among women. We showed that "optimal" (Community State Type (CST) I, II, and V) and "sub-optimal" (CST III) communities are more stable over time than "non-optimal" (CST IV) ones. Furthermore, we found that some covariates - most notably alcohol consumption - impacted the probability of shifting from one CST to another. We performed counterfactual simulations to confirm that alterations of key covariates, such as alcohol consumption, could shape the prevalence of different microbiota communities in the population. Finally, our analyses indicated that there is a relatively canalised pathway leading to the deterioration of vaginal microbiota communities, whereas the paths to recovery can be highly individualised among women. In addition to providing one of the first insights into vaginal microbiota dynamics over a year, our study showcases a novel application of a hierarchical Bayesian Markov model to clinical cohort data with many covariates. Our findings pave the way for an improved mechanistic understanding of microbial dynamics in the vaginal environment and the development of novel preventative and therapeutic strategies to improve vaginal health.

Persistent infection by high-risk human papillomavirus (HPV) genotypes has been identified as a necessary etiological factor in cervical cancer, with HPV16 alone accounting for approximately 50-60 % of these cases. Fortunately, the vast majority of genital HPV infections clear spontaneously within two years and without causing any symptoms. The mechanisms leading to this clearance, or more precisely absence of HPV detection, remain unclear. Yet, understanding the immunology of HPV clearance could help develop new biomarkers or therapies. Building on a longitudinal study of women with genital HPV infections, we analysed 100 samples using quantitative bulk RNA sequencing (RNA-seq) to identify potential host transcriptomic signatures associated with infection clearance in asymptomatic young women. Using Gene Set Enrichment Analysis (GSEA) to anaylse significantly enriched pathways across infection outcome categories, we found that HPV-positive infections were characterised by downregulation in both antiviral innate and adaptive immune responses. Additionally, amongst the HPV-positive infections, HPV16-positive infections were associated with downregulation of pathways related to the viral life cycle regulation. Furthermore, non-clearing infections were differentiated by adaptive immune response activation, and persistent infections were marked by downregulation of pathways related to tumor necrosis factor (TNF) production and regulation. This work represents one of the first transcriptomics analyses tackling asymptomatic HPV clearance. It suggests that adaptive immunity is the most prominent factor involved in HPV infection clearance and could be potentially used to further address future diagnostic and therapy-related challenges for HPV screening and prevention. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 648963, to SA) and the ExposUM Fellowship (to NT) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The PAPCLEAR 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), and is registered at ClinicalTrials.gov under the ID [NCT02946346][1]. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02946346&atom=%2Fmedrxiv%2Fearly%2F2025%2F10%2F13%2F2025.10.10.25337763.atom

Human papillomaviruses (HPVs) are the most oncogenic viruses known to humans, with 12 high-risk (HR) genotypes causing nearly all cervical cancers. Cytology is commonly used to screen for cervical lesions but is currently being replaced by testing for high-risk HPV (HR HPV). Although HR HPV screening has a higher sensitivity, its specificity is limited, and it is currently advised to repeat the first screening 4 to 6 months later. To increase the sensitivity of the screening triage, other biomarkers have been suggested, including HPV viral load. Indeed, since 1999, several independent studies have found an association between HR HPV viral load in cervical samples and the severity of cervical disease. Here, we further explore the determinants of variations in HPV viral load in genital infections in young adult women. We analysed samples collected in the PAPCLEAR clinical cohort for participants who were infected by HPV genotypes for which we quantified virus load using qPCR targeting 13 genotypes. We developed a Bayesian statistical model estimating the effect of covariates of interest on the HPV viral load. To analyse precisely the viral load difference between HPV genotypes, phylogenetic distances between HPVs were also integrated in the Bayesian model. Our results fail to identify an effect of anti-HPV vaccination, co-infections by multiple HPVs or tobacco smoking on the detected viral load. On the opposite, swabs contained significantly more viral copies than cervical smears. Our results also highlight that most of the viral load variance could be explained at the genotype level (80%) rather than at the individual level (20%). Our model reveals important differences in viral load detected between the different genotypes tested, with HPV16 being the highest and HPV18 the lowest. The impact of phylogenetic signal on viral load was also estimated to be low, except for a cluster comprised of HPV53, HPV66 and HPV56. These results contribute to identifying the main drivers of HPV viral load detected and could help design needed future screening policies. ### Competing Interest Statement JR reports personal fees from Gilead (consulting and payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), Janssen (payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), Merck (payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), Theratechnologies (payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), and ViiV Healthcare (consulting and payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events) and support for attending meetings and/or travel from Gilead and Pfizer, outside of the submitted work. All the other authors do not report any conflict of interest. ### Funding Statement This project was funded by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 648963). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The PAPCLEAR cohort study has been approved by the Comite de Protection des Personnes (CPP) Sud Mediterranee I (reference number 2016-A00712-49), the Comite Consultatif sur le Traitement de l'Information en matiere de Recherche dans le domaine de la Sante (reference number 16.504), the Commission Nationale Informatique et Libertes (reference number MMS/ABD/ AR1612278, decision number DR-2016-488), the Agence Nationale de Securite du Medicament et des Produits de Sante (reference 20160072000007), and is registered at [ClinicalTrials.gov][1] under the ID [NCT02946346][2]. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study will be made available upon publication in a peer reviewed journal. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02946346&atom=%2Fmedrxiv%2Fearly%2F2024%2F01%2F17%2F2024.01.17.24301437.atom

BACKGROUND:We studied the duration of HPV detection and risk of (re-) detection for 25 HPV genotypes in a cohort of 132 women followed every eight weeks for up to two years between 2016 and 2020. Participants were between 18 and 25 years old at inclusion and half of them were vaccinated against HPV. They were recruited near the University and the STI detection centre in Montpellier, France. METHODS:We used genotype-specific longitudinal data to characterise the dynamics of HPV-detected episodes. We investigated the contribution of viral and host factors to the variations in the duration of HPV detection, and the time before (re-)detection of the same genotype using multivariate Cox regression models with frailty at the patient level. FINDINGS:We detected at least one HPV episode in 74% of the participants and re-detected the same genotype in 47% of them. Covariates related to socio-economic difficulties were associated with a lower risk of detectability loss (hazard ratio 0.45 with a 95% confidence interval, CI, from 0.21 to 0.97). The number of lifetime sexual partners was strongly associated with an increased risk of new positive detection (hazard ratio 2.40 with a 95%CI from 1.07 to 5.39). In contrast, vaccination was associated with a lower risk of displaying incident infections (hazard ratio of 0.64 with a 95%CI from 0.43 to 0.96). CONCLUSION:In the short term, vaccination shows clear signs of protection against new HPV detections, including for some genotypes not targeted by the vaccine, such as HPV31 and HPV51.

Human papillomavirus (HPV) 16 is the most oncogenic biological agents for humans. However, essential quantitative aspects of its infection cycle remain inadequately characterized. Specifically, the proportion of infected cells and the viral copy number per infected cell in cervical smears are not well understood. To address this, we employed a combination of limiting dilution techniques and Bayesian statistics on routine cervical smears to estimate the frequency of infected cells and the viral copy number per cell. Our methodology was initially validated through numerical simulations and cell culture experiments. Subsequently, we analyzed 38 HPV16-positive cervical smears, comprising 26 samples from patients without cytological lesions and 12 from patients with low-grade lesions. Our findings indicated that the substantial variability in viral load across samples predominantly stemmed from differences in the frequency of infected cells. Additionally, the mean number of HPV copies per infected cell was consistently low across all samples, ranging from approximately 2.3 to 100 copies. However, in samples with low-grade lesionMarie-Paule Algross, this number was observed to double on average. These results challenge existing assumptions regarding the biology of HPV genital infections, which are typically asymptomatic or minimally symptomatic.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThe authors acknowledge further support from the Centre National de la Recherche Scientifique, the Institut de Recherche pour le Developpement, the Agence Nationale de la Recherche contre le Sida (ANRS-MIE, to NT) and to the Labex MemoLife (to BE).### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:HPV16-positive samples were stored in a biobank for which a declaration on the preparation and storage of human samples for research purposes has been validated by the Ministere de l'Enseignement Superieur et de la Recherche (Paris, France), with number DC-2014-2086. HPV-negative samples came from the study "Health in climacteric women belonging to NGOs. PAPILONG study", validated by the Ethical committee of the CEI DGSP-CSISP (Valencia, Spain), with number 20210604/10/01.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced are available online at https://gitlab.in2p3.fr/ete/hpv16\_copy\_number[https://gitlab.in2p3.fr/ete/hpv16\_copy\_number][1] [1]: https://gitlab.in2p3.fr/ete/hpv16_copy_number

Human papillomavirus (HPV) infections drive one in twenty new cancer cases. Despite the potential for improving treatment, screening, and vaccination strategies, little is known as to why most HPV infections clear spontaneously within two years. To untangle the dynamics of these non-persisting infections, we performed a combined quantitative analysis of virological, immunological, and clinical data from an original longitudinal cohort of 189 women with high temporal resolution. We find that HPV viral load reaches a plateau within two months, and clears within a median time of 14 months. Furthermore, we identify immune correlates associated with infection clearance, especially TCR-gamma-delta cells. Our results open new perspectives for understanding the frontier between acute and chronic infections and for controlling HPVassociated diseases.

Objectives HPV infections are ubiquitous. For most infections, we lose track of the presence of the virus in host in less than three years after the start of infection. The mechanisms regulating the persistence of HPV infection are still partially understood. In this work, we focus on incident HPV detection in young women and we characterise the dynamics of these infections and evaluate the effect of genotype and host socio-economic factors on the duration of HPV detection and time between detection. Methods We investigated human papillomavirus (HPV) genotype detection patterns in 182 young women in Montpellier, France. We relied on SPF10-LiPA25 screening assay for the simultaneous de-tection of 25 HPV genotypes. We used survival analysis tools with frailty effects to investigate the contribution of viral and host factors to variations in the time of HPV detectability, time of first incident detection, and time before re-detection. Results Women of the PAPCLEAR cohort experienced numerous positive HPV events, including frequent redetection of the same genotype. We retrieve classical results that HR-genotypes are detected for longer duration than LR-genotypes. HR-genotypes were also more liekly to be detected than LR-genotypes during the follow-up. The number of lifetime sexual partner was strongly associated with increased risk of new positive detection while vaccination was related to a lower risk of displaying incident infections. Covariates related to socio-economic difficulties were associated with longer duration of HPV positivity. Conclusions Young women display numerous event of HPV detection, with frequent codetections of multiple genotypes at the same time and redetection of the same type after periods of no detection. These new detection are almost certainly the result of new acquisition from sexual partners, with little evidence of re-emergence of latent infections. A better characterisation of transient infections might help unveil doubts and misconception on HPV physiopathology, favouring adherence to preventive policies. ### Competing Interest Statement J. R. reports personal fees from Gilead (consulting and payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), Janssen (payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), Merck (payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), Theratechnologies (payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), and ViiV Healthcare (consulting and payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events) and support for attending meetings and/or travel from Gilead and Pfizer, outside of the submitted work. All the other authors do not report any conflict of interest or personal relationships that could have appeared to influence the work reported in this paper. ### Funding Statement TB is funded by la Ligue contre le Cancer (grant No TAKX21133). This work was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 648963 to SA). The sponsor had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The PAPCLEAR trial was promoted by the Centre Hospitalier Universitaire de Montpellier and approved by the Comité de Protection des Personnes (CPP) Sud Méditerranée I on 11 May 2016 (CPP number 16 42, reference number ID RCB 2016A00712-49); by the Comité Consultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Santé on 12 July 2016 (reference number 16.504); and by the Commission Nationale Informatique et Libertés on 16 December 2016 (reference number MMS/ABD/AR1612278, decision number DR-2016488). This trial was authorised by the Agence Nationale de Sécurité du Médicament et des Produits de Santé on 20 July 2016 (reference 20160072000007). The [ClinicalTrials.gov][1] identifier is [NCT02946346][2]. All participants provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as [ClinicalTrials.gov][1]. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The raw data and R scripts used will be deposited on the Zenodo server upon publication. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02946346&atom=%2Fmedrxiv%2Fearly%2F2023%2F10%2F02%2F2023.09.30.23296382.atom

The vaginal ecosystem is a key component of women's health. It also represents an ideal system for ecologists to investigate the consequence of perturbations on species diversity and emerging properties between organizational levels. Here, we study how exposure to different types of menstrual products is linked to microbial, immunological, demographic, and behavioural measurements in a cohort of young adult women who reported using more often tampons (n = 107) or menstrual cups (n = 31). We first found that cup users were older and smoked less than tampon users. When analysing health indicators, we detected potential associations between cups use reporting and fungal genital infection. A multivariate analysis confirmed that in our cohort, reporting using cups over tampons was associated with the higher odds ratio to report a fungal genital infection diagnosis by a medical doctor within the last 3 months. We did not detect significant differences between groups in terms of their bacterial vaginal microbiota composition and found marginal differences in the level of expression of 20 cytokines. However, a multivariate analysis of these biological data identified some level of clustering based on the menstrual product type preferred (cups or tampons). These results suggest that exposure to different types of menstrual products could influence menstrual health. Larger studies and studies with a more powered setting are needed to assess the robustness of these associations and identify causal mechanisms.

Menstrual cups are gaining in popularity worldwide as a more environmentally sustainable and affordable alternative to disposable personal hygiene products. However, there is currently a lack of scientific literature regarding their safety and potential effects on women's health. We analysed biological, demographic, and behavioural data in a cohort of young adult women using either tampons (N = 81) or menstrual cups (N = 22). We identify an increased risk of being diagnosed with fungal infection for women using menstrual cups over tampons. We did not detect significant differences between groups in terms of vaginal microbiota composition or local cytokines expression profile. However we found that depending on the type of menstrual product they use more (cups or tampons), women fall into two different clusters in a factor analysis of mixed data, which potentially reflects differences in their local vaginal environments. These results underline the urgent need for in-depth studies to better understand the potential associations between menstrual product products and women's health.

Human papillomaviruses (HPVs) are oncogenic viruses causing most cervical cancers. Highly prevalent in young, sexually active women, only a minority of HPV infections persist. To better characterize the immuno-modulatory impact of early HPV infections, we measured changes in a panel of 20 cytokines in cervicovaginal samples collected from young women who were tested for HPV and self-reported for genital inflammation and infection symptoms. Multi-factor statistical analyses revealed that increased IL-1Alpha and IL-12/IL-23p40 concentrations were associated with HPV infection and that macrophage inflammatory proteins were associated in particular with high-risk HPV infections. ClinicalTrials.gov identifier NCT02946346.

AbstractObjectiveTo determine if the use of menstrual cups rather than tampons is associated with more or less health risk.DesignAnalysing biological, demographic, and behavioural data in a cohort of women who reported using mostly tampons (n = 81) or menstrual cups (n = 22).SettingA cross-sectional analysis using the inclusion data of a single centre longitudinal study.Population149 women from 18 to 25 years old living in the area of Montpellier (France) who reported having at least one new sexual partner over the last year.MethodsStatistical modelling (mainly binomial regression models and factor analyses of mixed data).Main Outcome MeasuresSelf-reported data from questionnaires (fungal infection, urinary tract infection, stress level) and biological data (HPV screening, vaginal microbiota profiling, circulating antibodies titration, and local cytokine concentrations).ResultsWe identify an increased risk of reporting fungal infections for women using menstrual cups over tampons. We do not detect significant differences in terms of vaginal microbiota composition or local cytokines expression profile but find that women fall into two different clusters in a factor analysis of mixed data depending on the type of menstrual product they use more (cups or tampons).ConclusionsThese results point to potential health risks in the use of menstrual cups and differences in local vaginal environments. In-depth studies are needed to better understand potential associations between menstrual product use and women’s health.FundingEuropean Research Council (EVOLPROOF, grant 648963)EthicsThe PAPCLEAR study ClinicalTrials.gov identifier is NCT02946346.Tweetable abstractA cross-sectional study finds a significant association between menstrual cup use and fungal infection risk.

Understanding genital infections by Human papillomaviruses (HPVs) remains a major public health issue, especially in countries where vaccine uptake is low. We investigate HPV prevalence and antibody status in 150 women (ages 18 to 25) in Montpellier, France. At inclusion and one month later, cervical swabs, blood samples and questionnaires (for demographics and behavioural variables) were collected. Oncogenic, non-vaccine genotypes HPV51, HPV66, HPV53, and HPV52 were the most frequently detected viral genotypes overall. Vaccination status, which was well-balanced in the cohort, showed the strongest (protective) effect against HPV infections, with an associated odds ratio for alphapapillomavirus detection of 0.45 (95% confidence interval: [0.22;0.58]). We also identified significant effects of age, number of partners, body mass index, and contraception status on HPV detection and on coinfections. Type-specific IgG serological status was also largely explained by the vaccination status. IgM seropositivity was best explained by HPV detection at inclusion only. Finally, we identify a strong significant effect of vaccination on genotype prevalence, with a striking under-representation of HPV51 in vaccinated women. Variations in HPV prevalence correlate with key demographic and behavioural variables. The cross-protective effect of the vaccine against HPV51 merits further investigation.

Introduction Human papillomaviruses (HPVs) are responsible for one-third of all cancers caused by infections. Most HPV studies focus on chronic infections and cancers, and we know little about the early stages of the infection. Our main objective is to better understand the course and natural history of cervical HPV infections in healthy, unvaccinated and vaccinated, young women, by characterising the dynamics of various infection-related populations (virus, epithelial cells, vaginal microbiota and immune effectors). Another objective is to analyse HPV diversity within hosts, and in the study population, in relation to co-factors (lifestyle characteristics, vaccination status, vaginal microbiota, human genetics). Methods and analysis The PAPCLEAR study is a single center longitudinal study following 150 women, aged 18–25 years, for up to 2 years. Visits occur every 2 or 4 months (depending on HPV status) during which several variables are measured, such as behaviours (via questionnaires), vaginal pH, HPV presence and viral load (via qPCR), local concentrations of cytokines (via MesoScale Discovery technology) and immune cells (via flow cytometry). Additional analyses are outsourced, such as titration of circulating anti-HPV antibodies, vaginal microbiota sequencing (16S and ITS1 loci) and human genotyping. To increase the statistical power of the epidemiological arm of the study, an additional 150 women are screened cross-sectionally. Finally, to maximise the resolution of the time series, participants are asked to perform weekly self-samples at home. Statistical analyses will involve classical tools in epidemiology, genomics and virus kinetics, and will be performed or coordinated by the Centre National de la Recherche Scientifique (CNRS) in Montpellier. Ethics and dissemination This study has been approved by the Comité de Protection des Personnes 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) and by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (reference 20160072000007). Results will be published in preprint servers, peer-reviewed journals and disseminated through conferences. Trial registration number NCT02946346 ; Pre-results.

Viruses belonging to the Dicistroviridae family have attracted a great deal of attention from scientists owing to their negative impact on agricultural economics, as well as their recent identification as potential aetiological agents of febrile illness in human patients. On the other hand, some Dicistroviruses are also studied for their potential biopesticide properties. To date, Dicistrovirus characterized in African mainland remain scarce. By using High-Throughput Sequencing technology on insectivorous bat faeces (Hipposideros Caffer) sampled in a cave used by humans to collect bat guano (bat manure) as fertilizer in Zimbabwe, we characterized the full-length sequences of three Dicistrovirus belonging to the Cripavirus and Aparavirus genus: Big Sioux River Virus-Like (BSRV-Like), Acute Bee Paralysis Virus (ABPV), and Aphid Lethal Paralysis Virus (ALPV). Phylogenetic analyses of ORF-1 and ORF-2 genes showed a complex evolutionary history between BSRV and close viruses, as well as for the Aparavirus genus. Herewith, we provide the first evidence of the presence of Dicistrovirus in Zimbabwe and highlight the need to further document the impact of such viruses on crops, as well as in beekeeping activities in Zimbabwe which represent a crucial source of income for Zimbabwean people.

Bats carry a great diversity of zoonotic viruses with a high-impact on human health and livestock. Since the emergence of new coronaviruses and paramyxoviruses in humans (e.g. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Nipah virus), numerous studies clearly established that bats can maintain some of these viruses. Improving our understanding on the role of bats in the epidemiology of the pathogens they harbour is necessary to prevent cross-species spill over along the wild/domestic/human gradient. In this study, we screened bat faecal samples for the presence of Coronavirus and Paramyxovirus in two caves frequently visited by local people to collect manure and/or to hunt bats in Zimbabwe. We amplified partial RNA-dependent RNA polymerase genes of Alpha and Betacoronavirus together with the partial polymerase gene of Paramyxovirus. Identified coronaviruses were related to pathogenic human strains and the paramyxovirus belonged to the recently described Jeilongvirus genus. Our results highlighted the importance of monitoring virus circulation in wildlife, especially bats, in the context of intense human-wildlife interfaces in order to strengthen prevention measures among local populations and to implement sentinel surveillance in sites with high zoonotic diseases transmission potential.

Enteroviruses (EVs) belong to the family Picornaviridae and are responsible for mild to severe diseases in mammals including humans and non-human primates (NHP). Simian EVs were first discovered in the 1950s in the Old World Monkeys and recently in wild chimpanzee, gorilla and mandrill in Cameroon. In the present study, we screened by PCR EVs in 600 fecal samples of wild apes and monkeys that were collected at four sites in Gabon. A total of 32 samples were positive for EVs (25 from mandrills, 7 from chimpanzees, none from gorillas). The phylogenetic analysis of VP1 and VP2 genes showed that EVs identified in chimpanzees were members of two human EV species, EV-A and EV-B, and those identified in mandrills were members of the human species EV-B and the simian species EV-J. The identification of two novel enterovirus types, EV-B112 in a chimpanzee and EV-B113 in a mandrill, suggests these NHPs could be potential sources of new EV types. The identification of EV-B107 and EV90 that were previously found in humans indicates cross-species transfers. Also the identification of chimpanzee-derived EV110 in a mandrill demonstrated a wide host range of this EV. Further research of EVs in NHPs would help understanding emergence of new types or variants, and evaluating the real risk of cross-species transmission for humans as well for NHPs populations.