title: The association between adverse pregnancy outcomes and maternal human papillomavirus infection: a systematic review protocol.
abstract: Human papillomavirus (HPV) is the most prevalent genital infection, especially in young women of reproductive age. In vitro and animal model experiments provide compelling evidence of the harmful effect of HPV on pregnancy outcomes, but results from epidemiologic studies are inconclusive. We aim to determine the strength of the relationship between adverse pregnancy outcomes (APO) and HPV infection and assess its consistency across studies, by systematically reviewing the literature.
  
  
  
  The search strategy has been developed on the basis of the PICOS framework: Population (pregnant women); Exposure (HVP infection confirmed by HPV testing); Comparator (pregnant women without HPV infection); Outcomes (miscarriage, spontaneous preterm birth, low birth weight, preterm premature rupture of membranes, pregnancy-induced hypertensive disorders and intrauterine growth restriction) and Study design (observational studies). We will search three information sources: (1) electronic databases (MEDLINE, EMBASE, and EBM Reviews databases); (2) Grey literature (Google Scholar and Web of Science conference proceedings); and (3) citing and cited articles of included studies. Two reviewers (JN, NZ) will independently and in duplicate screen identified articles, select eligible studies, and extract data. Discrepancies will be resolved by consensus and otherwise by discussion with the other authors (MHM, HT). Quality of included studies will be assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. We will narratively synthesize extracted data whether meta-analysis is conducted or not. Meta-analysis of each outcome will be performed, and where appropriate, an average measure of association will be computed. We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess and grade the strength of confidence in cumulative estimate.
  
  
  
  Comprehensive and high-quality evidence of a negative effect of HPV on pregnancy outcomes might be an additional motivation for HPV vaccination. Absence of such relationship could dispel anxiety and reassure HPV-infected pregnant women and clinicians. Findings of a poor level of confidence will allow identification of current knowledge gaps on HPV-pregnancy outcome relationship that need further research.
  
  
  
  PROSPERO CRD42016033425.
authors.affiliation: Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Pavilion 7101, Avenue du Parc, Montreal, QC, H3N 1X7, Canada.|Department of Social and Preventive Medicine, Sainte-Justine Hospital Research Center, Université de Montréal, 3175 Côte Sainte-Catherine, Room A-830, Montreal, H3T 1C5, QC, Canada.
authors.forename: Joseph
authors.identifier: 0000-0002-5983-6115
authors.initials: J
authors.lastname: Niyibizi
authors.affiliation: Department of Obstetrics and Gynecology, Research Centre of University of Montreal Hospital Centre (CRCHUM) and University of Montreal, Tour Saint-Antoine, 850, rue St-Denis, Montreal, QC, H2X 0A9, Canada.
authors.forename: Nadège
authors.initials: N
authors.lastname: Zanré
authors.affiliation: Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Pavilion 7101, Avenue du Parc, Montreal, QC, H3N 1X7, Canada.|Department of Obstetrics and Gynecology, Research Centre of University of Montreal Hospital Centre (CRCHUM) and University of Montreal, Tour Saint-Antoine, 850, rue St-Denis, Montreal, QC, H2X 0A9, Canada.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Mayrand
authors.affiliation: Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Pavilion 7101, Avenue du Parc, Montreal, QC, H3N 1X7, Canada. helen.trottier@umontreal.ca.|Department of Social and Preventive Medicine, Sainte-Justine Hospital Research Center, Université de Montréal, 3175 Côte Sainte-Catherine, Room A-830, Montreal, H3T 1C5, QC, Canada. helen.trottier@umontreal.ca.
authors.forename: Helen
authors.initials: H
authors.lastname: Trottier
mesh_terms: D005260:Female; D006801:Humans; D030361:Papillomavirus Infections / Q000150:complications*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology / Q000821:virology*; D011256:Pregnancy Outcome; D000078202:Systematic Reviews as Topic
keywords: Adverse pregnancy outcomes; Human papillomavirus; Pregnant women; Protocol; Systematic review