Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery

Abstract

Based on the current literature, we aimed to provide an overview on Human Papillomavirus prevalence in normal pregnancies and pregnancies with adverse outcome. We conducted a systematic literature search in PubMed and Embase. Data extracted from the articles and used for analysis included HPV prevalence, pregnancy outcome, geographical location, investigated tissue types, and HPV detection methods. The overall HPV prevalence in normal full-term pregnancies was found to be 17.5% (95% CI; 17.3-17.7) for cervix, 8.3% (95% CI; 7.6-9.1) for placental tissue, 5.7% (95% CI; 5.1-6.3) for amniotic fluid, and 10.9% (95% CI; 10.1-11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and preterm deliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50%, resp.), were identified to be higher compared to normal full-term pregnancies (P < 0.05 and P < 0.0001). Great variation in HPV prevalence was observed between study populations of different geographical locations. This review demonstrates an association between spontaneous abortion, spontaneous preterm delivery, and the presence of HPV in both the cervix and the placenta. However, a reliable conclusion is difficult to draw due to the limited number of studies conducted on material from pregnancies with adverse outcome and the risk of residual confounding.

Figure 1

Flow diagram of literature search. The flow diagram shows the search in the PubMed database. A supplementary search in the Embase database was conducted in the same way and resulted in three additional articles for data extraction and quantitative analysis.

Figure 2

HPV prevalence depends on the investigated tissue type. HPV prevalence in different tissue types of normal pregnancies in %. 38 studies have been included in the present analysis, N _cervix = 32, N _{placenta/abortion  product} = 9, N _{amniotic  fluid} = 4, and N _{umbilical  cord  blood} = 7. N indicates number of studies included. n indicates number of cases included. ^∗ P < 0.05, ^∗∗∗ P < 0.001, and ^∗∗∗∗ P < 0.0001.

Figure 3

Higher HPV prevalence detected in pregnancies with adverse outcome compared to normal pregnancies. HPV prevalence in normal pregnancies, spontaneous abortions, and spontaneous preterm deliveries in %. (a) In cervix. 34 studies have been included in the present analysis, N _Normal = 32, N _{Spontaneous  abortion} = 1, and N _{Preterm  delivery} = 2. (b) In placenta. 14 studies have been included in the present analysis, N _Normal = 9, N _{Spontaneous  abortion} = 6, and N _{Preterm  delivery} = 1. N indicated number of studies included. n indicates number of cases included. ^∗ P < 0.05, ^∗∗ P < 0.01, and ^∗∗∗∗ P < 0.0001.

Figure 4

HPV prevalence in normal pregnancies depends on geographical location. HPV prevalence in cervix of normal pregnancies in %. 32 studies have been included in the present analysis, N _Europe = 13, N _USA = 4, N _{Latin  America} = 5, and N _Asia = 10. N indicated number of studies included. n indicates number of cases included. ^∗∗ P < 0.01, ^∗∗∗∗ P < 0.0001.

Figure 5

HPV prevalence depends on time of sample collection and on the applied HPV detection method. (a) Cervical HPV prevalence in % at different time points of sample collection of normal pregnancies. 25 studies have been included in the present analysis, N _{1st  trimester} = 10, N _{2nd  trimester} = 10, N _{3rd  trimester} = 18, N _{at  birth} = 4, and N _postpartum = 4. (b) HPV prevalence in % in relation to the detection method used. Note that only two studies were using Southern blot as their main detection method. 45 studies have been included in the present analysis, N _PCR = 34, N _{hybrid  capture} = 8, N _{DNA  chip} = 5, and N _{Southern  blot} = 2. N indicated number of studies included. n indicates number of cases included. ^∗ P < 0.05, ^∗∗ P < 0.01, ^∗∗∗ P < 0.001, and ^∗∗∗∗ P < 0.0001; ns: not significant.