Investigation on Spontaneous Abortion and Human Papillomavirus Infection.

Mauro Tognon,John Charles Rotondo,Lucia Oton-Gonzalez,Fortunato Vesce,Carmen Lanzillotti,Chiara Mazziotta,Carlo Contini,Fernanda Martini,Federica Magagnoli,Andrea Tagliapietra

doi:10.3390/vaccines8030473

Abstract

Viral infections are considered to be risk factors for spontaneous abortion (SA). Conflicting results have been reported on the association between Human Papillomavirus (HPV) and SA. HPV DNA was investigated in matched chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from women who experienced SA (n = 80, cases) and women who underwent a voluntary interruption of pregnancy (VI; n = 80, controls) by qualitative PCR and quantitative droplet digital PCR (ddPCR). Viral genotyping was performed using real-time PCR in HPV-positive samples. Specific IgG antibodies against HPV16 were investigated in sera from SA (n = 80) and VI (n = 80) females using indirect ELISA assays. None of the DNA samples from SA subjects was HPV-positive (0/80), whilst HPV DNA was detected in 2.5% of VI women (p > 0.05), with a mean viral DNA load of 7.12 copy/cell. VI samples (n = 2) were found to be positive for the HPV45 genotype. The ddPCR assay revealed a higher number of HPV-positive samples. HPV DNA was detected in 3.7% and 5% of SA and VI chorionic tissues, respectively, with mean viral DNA loads of 0.13 copy/cell in SA and 1.79 copy/cell in VI (p >0.05) samples. All DNA samples from the PBMCs of SA and VI females tested HPV-negative by both PCR and ddPCR. The overall prevalence of serum anti-HPV16 IgG antibodies was 37.5% in SA and 30% in VI (p > 0.05) women. For the first time, HPV DNA was detected and quantitatively analyzed using ddPCR in chorionic villi tissues and PBMCs from SA and VI women. Circulating IgG antibodies against HPV16 were detected in sera from SA and VI females. Our results suggest that HPV infection in chorionic villi may be a rare event. Accordingly, it is likely that HPV has no significant role in SA.

Highlights

Spontaneous abortion (SA) is the unintentional loss of the embryo or fetus before the 20th week of gestation [1]
Our results suggest that Human Papillomavirus (HPV) infection in chorionic villi may be a rare event
HPV DNA sequences were investigated in 320 samples, including 80 chorionic villi and 80 peripheral blood mononuclear cells (PBMCs) from SA females (n = 80) and 80 chorionic villi and 80 PBMCs from voluntary interruption of pregnancy (VI) females (n = 80, employed as a control)

Summary

Introduction

Spontaneous abortion (SA) is the unintentional loss of the embryo or fetus before the 20th week of gestation [1]. Spontaneous embryo/fetus loss is considered the most common adverse complication during pregnancy [2,3,4]. The estimated SA occurrence, which varies according to the study population in question, is about 12–15% of clinical gestations [5]. 80% of SAs occur in the first trimester of pregnancy (first 12 weeks) [6], whereas 30% of pregnancies are lost between implantation and the sixth week [5]. The risk of SA occurrence directly increases with age, from 10–25% up to. 60–70% in pregnant females under 25 years old and over 40 years of age, respectively [7].

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Conclusion