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1. An outreach strategy to increase uptake of vaginal self-sampling for cervical cancer screening in older French women: The RIDECA interventional research protocol

Author

Olivier Lareyre, Caroline Mollevi, Guillaume Broc, Marie-Nina Caspar, Gergana Pehlivanska, Hélène Boyer, Soraya Groc, Giulia Corradi, Silvia Loy-Morel, Marine Guy, Nathalie Tricheux, Florence Cousson-Gélie, and Nathalie Boulle

Subjects
Medicine
Abstract

Background: In France, approximately 40% of women, including menopausal women, do not participate in cervical cancer screening. Many studies and meta-analyses have shown that self-sampling devices for high-risk human papillomavirus (HR-HPV) testing are valuable tools to increase participation. The success of self-sampling screening strategies depends on several factors, including the manner and circumstances in which the women are invited to participate. The acceptability and effectiveness of these strategies should be evaluated before further implementation. Objectives: The primary objective is to evaluate the uptake of cervical cancer screening in under-screened women, based on a direct offer of a vaginal self-sampling device by a midwife. Design: RIDECA is an interventional research project located in the South of France. Methods and Analysis: Six hundred women aged 50–65 with no cervical smear or HR-HPV test for 3 years or more will be recruited at two sites. The device will be offered to enrolled women to utilize at home and return to the Montpellier Hospital laboratory for HR-HPV testing. Completion of self-sampling by women who have accepted the device and follow-up of those with positive HR-HPV DNA tests will be monitored. During recruitment, participants will complete questionnaires on their socio-economic environment and motivational factors based on the psychosocial I-Change model. Semi-structured interviews will be conducted with a sub-group to identify barriers and levers to participation. Statistical analyses will be conducted for the full research sample and for each recruitment site. Ethics: The project was approved by the Ethical Research Committee Ile de France VI and by the French Data Protection Authority. Discussion: The results will provide useful information on the effectiveness (acceptability, efficiency) of this outreach strategy and identify barriers and levers that facilitate its implementation. Registration: ClinicalTrials.gov (NCT04716127), January 20, 2021.

Published
2024
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2. Concomitant and productive genital infections by HSV-2 and HPV in two young women: A case report

Author

Ilkay Başak Uysal, Vanina Boué, Carmen Lia Murall, Christelle Graf, Christian Selinger, Christophe Hirtz, Claire Bernat, Jacques Ravel, Jacques Reynes, Marine Bonneau, Massilva Rahmoun, Michel Segondy, Nathalie Boulle, Sophie Grasset, Soraya Groc, Tim Waterboer, Vincent Tribout, Ignacio G. Bravo, Sonia Burrel, Vincent Foulongne, Samuel Alizon, and Nicolas Tessandier

Subjects
Human papillomavirus, Herpes Simplex Virus-2, Co-infection, Interaction, Vaginal microbiota, qPCR, Infectious and parasitic diseases, RC109-216
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.

Published
2022
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3. Viral and immune dynamics of HPV genital infections in young women

Author

Nicolas Tessandier, Baptiste Elie, Vanina Boué, Christian Selinger, Massilva Rahmoun, Claire Bernat, Sophie Grasset, Soraya Groc, Anne-Sophie Bedin, Thomas Beneteau, Marine Bonneau, Christelle Graf, Nathalie Jacobs, Tsukushi Kamiya, Marion Kerioui, Julie Lajoie, Imène Melki, Jean-Luc Prétet, Bastien Reyné, Géraldine Schlecht-Louf, Mircea T. Sofonea, Olivier Supplisson, Vincent Foulongne, Jérémie Guedj, Christophe Hirtz, Marie-Christine Picot, Jacques Reynes, Vincent Tribout, Édouard Tuaillon, Tim Waterboer, Michel Segondy, Ignacio G Bravo, Nathalie Boulle, Carmen Lia Murall, and Samuel Alizon

Abstract

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.

Published
2023

4. Does exposure to different menstrual products affect the vaginal environment?

Author

Nicolas Tessandier, Ilkay Başak Uysal, Baptiste Elie, Christian Selinger, Claire Bernat, Vanina Boué, Sophie Grasset, Soraya Groc, Massilva Rahmoun, Bastien Reyné, Noemi Bender, Marine Bonneau, Christelle Graf, Vincent Tribout, Vincent Foulongne, Jacques Ravel, Tim Waterboer, Christophe Hirtz, Ignacio G. Bravo, Jacques Reynes, Michel Segondy, Carmen Lia Murall, Nathalie Boulle, Tsukushi Kamiya, and Samuel Alizon

Subjects
Genetics, Ecology, Evolution, Behavior and Systematics
Abstract

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.

Published
2022

5. Increased risk of fungal infection detection in women using menstrual cups vs. tampons: a cross-sectional study

Author

Nicolas Tessandier, Ilkay Başak Uysal, Baptiste Elie, Christian Selinger, Claire Bernat, Vanina Boué, Sophie Grasset, Soraya Groc, Tsukushi Kamiya, Massilva Rahmoun, Bastien Reyné, Noemi Bender, Marine Bonneau, Christelle Graf, Vincent Tribout, Vincent Foulongne, Jacques Ravel, Tim Waterboer, Christophe Hirtz, Ignacio G Bravo, Jacques Reynes, Michel Segondy, Carmen Lia Murall, Nathalie Boulle, and Samuel Alizon

Abstract

ObjectiveTo 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.

Published
2021

6. Receptor binding domain‐IgG levels correlate with protection in residents facing SARS‐CoV‐2 B.1.1.7 outbreaks

Author

Delphine Muriaux, Amandine Pisoni, Edouard Tuaillon, Brigitte Montes, Sophia Rafasse, Stéphanie Miot, Nejm Si-Mohamed, Clémence Niel, Lucie Gamon, Soraya Groc, Jean Bousquet, Hubert Blain, Anne-Marie Dupuy, Nathalie Gros, Yves Rolland, Valentin Delpui, Marie-Christine Picot, Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut de Recherche en Infectiologie de Montpellier (IRIM), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], efficacy, Immunology, Death risk, nucleocapsid antigenemia, nursing homes, Antibodies, Viral, SARS‐CoV‐2, Disease Outbreaks, 03 medical and health sciences, 0302 clinical medicine, COVID‐19, Internal medicine, Humans, Immunology and Allergy, Medicine, neutralizing antibodies, 030212 general & internal medicine, BNT162 Vaccine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Vaccines, 0303 health sciences, BNT162b2 vaccine, biology, SARS-CoV-2, business.industry, Incidence (epidemiology), COVID-19, Outbreak, antibody response, Vaccine efficacy, 3. Good health, Immunoglobulin G, residents, biology.protein, symptoms, Original Article, Basic and Translational Allergy Immunology, ORIGINAL ARTICLES, Antibody, business, Nursing homes
Abstract

Background Limited information exists on nursing home (NH) residents regarding BNT162b2 vaccine efficacy in preventing SARS‐CoV‐2 and severe COVID‐19, and its association with post‐vaccine humoral response. Methods 396 residents from seven NHs suffering a SARS‐CoV‐2 B.1.1.7 (VOC‐α) outbreak at least 14 days after a vaccine campaign were repeatedly tested using SARS‐CoV‐2 real‐time reverse‐transcriptase polymerase chain reaction on nasopharyngeal swab test (RT‐qPCR). SARS‐CoV‐2 receptor‐binding domain (RBD) of the S1 subunit (RBD‐IgG) was measured in all residents. Nucleocapsid antigenemia (N‐Ag) was measured in RT‐qPCR‐positive residents and serum neutralizing antibodies in vaccinated residents from one NH. Results The incidence of positive RT‐qPCR was lower in residents vaccinated by two doses (72/317; 22.7%) vs one dose (10/31; 32.3%) or non‐vaccinated residents (21/48; 43.7%; p < .01). COVID‐19–induced deaths were observed in 5 of the 48 non‐vaccinated residents (10.4%), in 2 of the 31 who had received one dose (6.4%), and in 3 of the 317 (0.9%) who had received two doses (p = .0007). Severe symptoms were more common in infected non‐vaccinated residents (10/21; 47.6%) than in infected vaccinated residents (15/72; 21.0%; p = .002). Higher levels of RBD‐IgG (n = 325) were associated with a lower SARS‐CoV‐2 incidence. No in vitro serum neutralization activity was found for RBD‐IgG levels below 1050 AU/ml. RBD‐IgG levels were inversely associated with N‐Ag levels, found as a risk factor of severe COVID‐19. Conclusions Two BNT162b2 doses are associated with a 48% reduction of SARS‐CoV‐2 incidence and a 91.3% reduction of death risk in residents from NHs facing a VOC‐α outbreak. Post‐vaccine RBD‐IgG levels correlate with BNT162b2 protection against SARS‐CoV‐2 B.1.1.7., This study assesses the incidence of positive SARS‐CoV‐2 B.1.1.7 by RT‐qPCR results according to the vaccination status in nursing home residents facing a VOC‐α outbreak. Two BNT162b2 doses are associated with a major reduction of SARS‐CoV‐2 B.1.1.7 incidence and COVID‐19. Post‐vaccine RBD‐IgG levels correlate with protection in this population.

Published
2021

7. RBD-IgG levels correlate with protection in Residents Facing SARS-CoV-2 B.1.1.7 Outbreaks

Author

Anne-Marie Dupuy, Amandine Pisoni, Jean Bousquet, Hubert Blain, Edouard Tuaillon, Nejm Si-Mohamed, Sophia Rafasse, Valentin Delpui, Marie-Christine Picot, Stéphanie Miot, Lucie Gamon, Clémence Niel, Yves Rolland, Soraya Groc, Brigitte Montes, Nathalie Gros, and Delphine Muriaux

Subjects
medicine.medical_specialty, biology, Coronavirus disease 2019 (COVID-19), business.industry, Incidence (epidemiology), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Outbreak, Vaccine efficacy, Internal medicine, Neutralization test, medicine, biology.protein, Antibody, Risk factor, business
Abstract

Background Limited information exists on nursing home (NH) residents regarding BNT162b2/Pfizer vaccine efficacy in preventing SARS-CoV-2 and severe Covid-19, and its association with post-vaccine humoral response. Methods 396 residents from seven NHs suffering a SARS-CoV-2 B.1.1.7 (VOC-α) outbreak at least 14 days after a vaccine campaign were repeatedly tested using SARS-CoV-2 real-time reverse-transcriptase polymerase chain reaction on nasopharyngeal swab test (RT-PCR). SARS-CoV-2 Receptor-Binding Domain (RBD) of the S1 subunit (RBD-IgG) was measured in all residents. Nucleocapsid antigenemia (N-Ag) was measured in RT-PCR-positive residents, and serum neutralizing antibodies in vaccinated residents from one NH. Results The incidence of positive RT-PCR was lower in residents vaccinated by two doses (22.7%) vs one dose (32.3%) or non-vaccinated residents (43.7%)(pConclusions Two BNT162b2/Pfizer doses are associated with a 48% reduction of SARS-CoV-2 incidence and a 91.3% reduction of death risk in residents from NHs facing a VOC-α outbreak. BNT162b2/Pfizer efficacy was partly predicted by post-vaccine RBD-IgG levels.

Published
2021

8. Cytokine response following perturbation of the cervicovaginal milieu during HPV genital infection

Author

Vanina Boué, Carmen Lía Murall, Nathalie Jacobs, Claire Bernat, Massilva Rahmoun, Soraya Groc, Marine Bonneau, Jacques Reynes, Samuel Alizon, Christophe Hirtz, Christelle Graf, Christian Selinger, Sophie Grasset, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Liège, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Project: 648963,H2020,ERC-2014-CoG,EVOLPROOF(2015), Génétique et évolution des maladies infectieuses (GEMI), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Alizon, Samuel, Are HPV vaccines ‘evolution-proof’? Multilevel evolutionary ecology of human oncoviruses - EVOLPROOF - - H20202015-09-01 - 2020-08-31 - 648963 - VALID, and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
0301 basic medicine, Allergy, Cervix Uteri, Alphapapillomavirus, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 0302 clinical medicine, Mucosal immunity, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Interleukin-1alpha, Medicine, Longitudinal Studies, Macrophage inflammatory protein, 0303 health sciences, Chlamydia, Interleukin-12 Subunit p40, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], HPV infection, virus diseases, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], female genital diseases and pregnancy complications, 3. Good health, Cytokine response, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Vagina, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cytokines, Female, Bacterial vaginosis, medicine.symptom, Oncovirus, Adult, Adolescent, Immunology, Natural history, Inflammation, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Young Adult, 03 medical and health sciences, Sexually active, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Humans, Sex organ, 030304 developmental biology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, 030203 arthritis & rheumatology, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], business.industry, Macrophages, Papillomavirus Infections, Cancer, Human Papillomavirus, medicine.disease, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030104 developmental biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

Human papillomaviruses (HPVs) are the most oncogenic viruses known to human, causing nearly all cervical cancers worldwide. Highly prevalent in young, sexually active women, most HPV infections are cleared within 3 years, and only a minority of those infections persist and lead to cancer later in life. To better characterize the immuno-modulatory impact of early HPV infection and more generally perturbations of the cervicovaginal milieu, we measured changes in a panel of 20 cytokines, known as highly dynamic effector molecules implicated in cell signaling. We analyzed 92 cervicovaginal samples collected from young, sexually active women who were tested for or diagnosed with HPV, chlamydia, and bacterial vaginosis. Also, symptoms associated with genital inflammation and infection were collected through self-reporting.Following a parsimonious multi-factor modeling approach, our statistical analyses revealed that increased IL-1Alpha and IL-12/IL-23p40 concentrations were associated with HPV infection. Cytokine network analysis further highlighted the role of IL-1Alpha and macrophage inflammatory proteins (MIP-3Alpha) in HPV-associated immuno-modulation.

Published
2021

9. HPV cervical infections and serological status in vaccinated and unvaccinated women

Author

Bastien Reyné, E. Picot, Tim Waterboer, Vanina Boué, Michel Segondy, Sophie Grasset, Carmen Lía Murall, Ignacio G. Bravo, Jacques Reynes, Soraya Groc, Christian Selinger, Claire Bernat, Massilva Rahmoun, Vincent Tribout, Nathalie Boulle, Samuel Alizon, Noemi Bender, Marine Bonneau, Christelle Graf, Marie-Christine Picot, Vincent Foulongne, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Biopathologie [CHRU Montpellier], Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Evolution Théorique et Expérimentale (MIVEGEC-ETE), Perturbations, Evolution, Virulence (PEV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Project: 648963,H2020,ERC-2014-CoG,EVOLPROOF(2015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), and Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)

Subjects
cross-protection, Genital infections, Uterine Cervical Neoplasms, serology, Alphapapillomavirus, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Serology, 0302 clinical medicine, acute infections, Genotype, Prevalence, 030212 general & internal medicine, Papillomaviridae, genital infections, biology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Vaccination, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Infectious Diseases, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, Female, France, Antibody, Cross-protection, Adult, medicine.medical_specialty, HPV, food.ingredient, Adolescent, 030231 tropical medicine, Young Adult, 03 medical and health sciences, food, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Internal medicine, medicine, genital infections 1, Humans, Papillomavirus Vaccines, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], General Veterinary, General Immunology and Microbiology, business.industry, Public health, Papillomavirus Infections, Public Health, Environmental and Occupational Health, Odds ratio, vaccination, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Confidence interval, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, Body mass index, Acute infections, Demography, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

Background Understanding genital infections by Human papillomaviruses (HPVs) remains a major public health issue, especially in countries where vaccine uptake is low. Methods 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. Results 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. Conclusions Variations in HPV prevalence correlate with key demographic and behavioural variables. The cross-protective effect of the vaccine against HPV51 merits further investigation.

Published
2020

10. Natural history, dynamics, and ecology of human papillomaviruses in genital infections of young women: protocol of the PAPCLEAR cohort study

Author

Guillaume Christophe, Aziza Seddiki, Ignacio G. Bravo, Christian Selinger, Julie Lajoie, Mathilde Buisson, Vincent Foulongne, Jacques Ravel, Giuseppe D'Auria, Vanina Boué, Martine Teirlinck, Carmen Lía Murall, Marine Bonneau, Edouard Tuaillon, Rémy Froissart, Christelle Graf, Nathalie Jacobs, Frédérique Lorcy, Thérèse Rousset, Tim Waterboer, Florence De Taroni, Jacques Reynes, E. Picot, Nathalie Boulle, Soraya Groc, Samuel Alizon, Claire Bernat, Christophe Hirtz, Massilva Rahmoun, Audrey Jaussent, Monique Baldellou, Vincent Tribout, Michel Segondy, Sophie Grasset, Marie-Christine Picot, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Virostyle (MIVEGEC-Virostyle), Perturbations, Evolution, Virulence (PEV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Perturbations & Virulence in Populations & Communities (MIVEGEC-Perturbations & Virulence in Populations & Communities ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CIBER de Epidemiología y Salud Pública (CIBERESP), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Laboratoire de Virologie [CHRU Montpellier], Du gène à l'écosystème (MIVEGEC-GeneSys), Pathogènes, Environnement, Santé Humaine (EPATH), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Manitoba [Winnipeg], University of Maryland School of Medicine, University of Maryland System, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Research), Université de Liège, Evolution Théorique et Expérimentale (MIVEGEC-ETE), Immunopathologie de l'Inflammation, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Washington [Seattle], Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre International de Recherches Médicales de Franceville, Laboratoire de Pathologie Comparée (LPC), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute of Research in Biotherapy, Laboratory of Biochemistry and Clinical Proteomics, Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institute for Genomic Sciences, School of Medicine (IGS), Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cellular and Molecular Immunology, GIGA-Research, university hospital, University Hospital, Alizon, Samuel, Génétique et évolution des maladies infectieuses (GEMI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Génétique et évolution des maladies infectieuses (GEMI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Longitudinal study, viruses, [SDV]Life Sciences [q-bio], viral kinetics, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 0302 clinical medicine, Clinical Protocols, Surveys and Questionnaires, Epidemiology, Protocol, [SDV.EE.ECO] Life Sciences [q-bio]/Ecology, environment/Ecosystems, Longitudinal Studies, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], persistence, General Medicine, Hydrogen-Ion Concentration, Viral Load, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Natural history, Infectious Diseases, Vagina, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cytokines, Population study, Female, France, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, Viral load, Cohort study, HPV, medicine.medical_specialty, Adolescent, Young Adult, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, [SDV.BID.SPT] Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, microbiota, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], medicine, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Genotyping, 030304 developmental biology, Gynecology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], business.industry, Papillomavirus Infections, [SDV.EE.IEO] Life Sciences [q-bio]/Ecology, environment/Symbiosis, virus load, immunity, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Human genetics, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, acute infection, Genital Diseases, Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

IntroductionHuman 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 analysisThe 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 disseminationThis 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 numberNCT02946346; Pre-results.

Published
2019

11. High prevalence and diversity of hepatitis B and hepatitis delta virus in Gabon

Author

Dieudonné Nkoghe, Jessica L. Abbate, Eric M. Leroy, Benjamin Roche, Athenaïs Gerber, Jean-Louis Albert, Pierre Becquart, Edouard Tuaillon, Soraya Groc, Frédéric Le Gal, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM U955, équipe 18, Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Microbiologie Clinique, Hôpital Avicenne, Centre National de Référence des Virus des Hépatites B C et Delta, Bobigny, France, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre International de Recherches Médicales de Franceville (CIRMF), Zoonoses virales et MTN (MIVEGEC-VIROZ), Biologie des infections virales: Emergence, DIFfusion, Impact, Contrôle, Elimination (EDIFICE), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre de Recherches Ecologiques et Evolutives sur le Cancer (MIVEGEC-CREEC), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), and Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord])

Subjects
Male, HBsAg, viruses, genotype, medicine.disease_cause, 0302 clinical medicine, Risk Factors, Seroepidemiologic Studies, Prevalence, 030212 general & internal medicine, Phylogeny, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, education.field_of_study, seroprevalence, virus diseases, Hepatitis B, hepatitis D virus, Middle Aged, Hepatitis D, 3. Good health, Infectious Diseases, RNA, Viral, 030211 gastroenterology & hepatology, Female, Hepatitis D virus, Hepatitis Delta Virus, Adult, Hepatitis B virus, Adolescent, Genotype, Population, Biology, Virus, 03 medical and health sciences, Young Adult, Virology, parasitic diseases, medicine, Seroprevalence, Humans, Gabon, Hepatitis Antibodies, education, Genotyping, Aged, Hepatology, Genetic Variation, Sequence Analysis, DNA, medicine.disease, Cross-Sectional Studies, hepatitis B virus, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Although central Africa is classified as having a high endemicity of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection, there is paucity of prevalence studies. For the first time on a country-wide level in Central Africa, we show in Gabon an overall 7.4% prevalence of Hepatitis B surface antigen (HBsAg) and that more than 25% of the HBsAg-positive population are infected by HDV. Although HBV prevalence did not differ significantly between provinces, there is a north-south split in the distribution of HDV seroprevalence, with the highest rates (>66.0%) correlating with the presence of specific ethnic groups in the northeastern provinces. Genotyping revealed high genetic diversity of the HBV and HDV strains circulating in Gabon, including many restricted to this region of the globe. This work confirmed that high exposure to HBV and HDV infection reported in selected regions of Gabon holds true across the whole country.

Published
2018

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