The association between adverse pregnancy outcomes and maternal human papillomavirus infection: a systematic review protocol

Abstract

BackgroundHuman 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.MethodsThe 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.DiscussionComprehensive 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.Systematic review registrationPROSPERO CRD42016033425 Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-017-0443-5) contains supplementary material, which is available to authorized users.

Is HPV vaccination of pregnant women really safe?

“…Ambuhl showed that HPV infection, alone, is significantly associated with, and may cause, spontaneous abortions and preterm deliveries (Ambuhl, ); these findings are supported by Niyibizi, Zanré, Mayrand, & Trottier () and Cho []. Mosbah, Barakat, Nabiel, & Barakat () found an association between active HPV infection and spontaneous preterm labor, and showed a direct correlation between viral load and preterm labor.…”

Human Papillomavirus Infections in Pregnant Women and Its Impact on Pregnancy Outcomes: Possible Mechanism of Self-Clearance

“…It has also been reported in various studies that within 1-2 years of HPV infection almost 80% of them resolve spontaneously [15]. Various studies suggested that during pregnancy it is more likely to acquire and progress HPV infection [16] which regresses after delivery [6,7,17,18].…”

“…The changed immune response and hormonal milieu during pregnancy might favor the presence or persistence of the HPV infection. Niyibizi et al [18] reported the prevalence of HPV infection in pregnant women with a wide variation from 5.5 to 65%. Various HPVs in several populations have been reported to be associated with adverse pregnancy outcomes such as preeclamsia, preterm rupture of membranes (PROM), preterm delivery, fetal growth restriction and placental abnormalities.…”

Mode of delivery does not have a relationship with high-risk HPV positivity

“…As it is already known, HPV is the most common sexually transmitted infection in adults [12]. In previous researches, maternal infections, inflammation [13], and changes in vaginal bacterial microbiota [14] have been recognised as an underlying cause of major adverse pregnancy outcomes: miscarriage [15], spontaneous preterm birth [16], and hypertensive disorders related to pregnancy [17,18].…”