title: Risk of autoimmune diseases and human papilloma virus (HPV) vaccines: Six years of case-referent surveillance.
abstract: BACKGROUND
  Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization.
  
  
  OBJECTIVE
  To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France.
  
  
  METHODS
  Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11-25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barré syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008-2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations.
  
  
  RESULTS
  With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41-0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results.
  
  
  CONCLUSIONS
  Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.
authors.affiliation: LASER Analytica, 10 Place de Catalogne, 75014 Paris, France; Conservatoire National des Arts et Métiers, 292 Rue Saint-Martin, 75003 Paris, France. Electronic address: Lamiae.Grimaldi@la-ser.com.
authors.forename: Lamiae
authors.initials: L
authors.lastname: Grimaldi-Bensouda
authors.affiliation: LASER Analytica, 10 Place de Catalogne, 75014 Paris, France; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, 1,020 Pine ave. West, Montréal, Québec, H3A 1A2, Canada. Electronic address: Michel.Rossignol@mcgill.ca.
authors.forename: Michel
authors.initials: M
authors.lastname: Rossignol
authors.affiliation: Service de Rhumatologie Pédiatrie, Centre Hospitalier Universitaire (CHU) Kremlin Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin-Bicêtre, 3 Avenue Victoria, 75004 Paris, France; Centre de Référence des Maladies Auto-Inflammatoires (CeRéMAI), CHU de Bicêtre, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Koné-Paut
authors.affiliation: Département de Médecine Interne et Endocrinologie, Hôpital Universitaire Avicenne, Université de Paris, 125 Rue de Stalingrad, 93000 Bobigny, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Krivitzky
authors.affiliation: Département de Neurologie, CHU de Nice, 4 Avenue Reine Victoria, 06003 Nice, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Lebrun-Frenay
authors.affiliation: Service de Rhumatologie Pédiatrique, Centre de compétence des Arthrites Juvéniles Idiopathiques et des Maladies auto-inflammatoires, Hôpital des enfants, Place Amélie Raba Léon, 33000 Bordeaux, France.
authors.forename: Johanna
authors.initials: J
authors.lastname: Clet
authors.affiliation: Département de Neurologie, CHU de Toulouse, Place du Docteur Baylac, TSA 40031 - 31059, Toulouse, France.
authors.forename: David
authors.initials: D
authors.lastname: Brassat
authors.affiliation: Département de Neurologie, AP-HP, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, 75013 Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Papeix
authors.affiliation: Endocrinologie, Diabétologie, Nutrition Pédiatriques, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, 2 Avenue Doyen Jean Lépine, 69500 Bron, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Nicolino
authors.affiliation: Service d'Endocrinologie-Diabétologie - maladies de la nutrition, CHU Grenoble Alpes, Boulevard de la Chantourne, 38700 La Tronche, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Benhamou
authors.affiliation: Service de Médecine Interne, CHU de Caen, Avenue de la Côte de Nacre, 14003 Caen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Fain
authors.affiliation: Service de Médecine Interne, Hôpital Cochin, AH-HP, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Costedoat-Chalumeau
authors.affiliation: Service d'Hémato-Immuno-Oncologie Pédiatrie, Hôpital Armand-Trousseau, AP-HP, 26 Avenue du Dr Arnold Netter, 75012 Paris, France.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Courcoux
authors.affiliation: Service de Médecine Interne et Maladies Infectieuses, CHU de Bordeaux, 1, rue Jean Burguet, 33000 Bordeaux, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Viallard
authors.affiliation: Centre de référence des cytopénies auto-immunes de l'adulte, Service de Médecine Interne, CHU Henri Mondor, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Godeau
authors.affiliation: Département de Médecine Interne, Hôpital Bichat, Université Paris Diderot, AP-HP, 46 Rue Henri Huchard, 75018 Paris, France; INSERM U1149, 16 rue Henri Huchard, 75890 Paris, France; Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and REmodelling in Renal and Respiratory Diseases), Université Paris Diderot, PRES Sorbonne Paris Cité, 5 Rue Thomas Mann, 75013, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Papo
authors.affiliation: Université de Lille, CHU Lille, LIRIC - INSERM U995, FHU Imminent, Hôpital Claude Huriez, Rue Michel Polonovski, 59037 Lille, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Vermersch
authors.affiliation: Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 55 Avenue de Paris, 78000 Versailles, France; Inserm U1016, Institut Cochin, Department of Immunology, 22 Rue Mechain, 75014 Paris, France; UF de dermatologie-immunologie clinique, Hôpital Ambroise Paré, AP-HP, 9 Avenue Charles de Gaulle, 92100 Boulogne-Billancourt, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bourgault-Villada
authors.affiliation: Inserm UMR 1153, Équipe de recherche en épidémiologie obstétricale, périnatale et pédiatrique (EPOPé), Centre de recherche épidémiologie et statistique Sorbonne Paris Cité, DHU risques et grossesse, Université Pierre et Marie Curie, 1 place du Parvis Notre-Dame, 75004 Paris, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Breart
authors.affiliation: LASER Europe Ltd, London, 66 Chiltern St, London W1U 4JT, United Kingdom; Department of Epidemiology, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK.
authors.forename: Lucien
authors.initials: L
authors.lastname: Abenhaim
mesh_terms: D000293:Adolescent; D000328:Adult; D001327:Autoimmune Diseases / Q000453:epidemiology* / Q000209:etiology*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D016017:Odds Ratio; D030361:Papillomavirus Infections / Q000150:complications / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000009:adverse effects* / Q000276:immunology; D011159:Population Surveillance; D012306:Risk; D055815:Young Adult
chemical_list: D053918:Papillomavirus Vaccines
keywords: Autoimmune disease; HPV vaccine; Pharmacoepidemiology