Human papillomavirus in foetal and maternal tissues from miscarriage cases

Abstract

Early miscarriage is still a concern, and viral infections are recognised as one of the causes of this adverse outcome. The causal relationship between HPV and miscarriage remains controversial. The aim of the study was to evaluate whether HPV infection indeed may occur in both the maternal and placental tissue in cases of miscarriage. Decidual and chorionic villi fragments (n = 118) were dissected from 81 miscarriage cases, 68 spontaneous and 13 intentional. HPV DNA was detected using the consensus primers MY09/11; in eight cases (9.9%, 8/81), seven of which (10.3%) were from spontaneous miscarriages and one (7.7%), was from an intentional miscarriage. The deciduas (4/8) and chorionic villi (5/8) were both infected with HPV. A reverse line blot was used to genotype HPV positive samples and revealed HPV6, 11, 58, 66 and 82. Although the results obtained cannot infer an association between HPV and pregnancy loss, it cannot be ruled out. Impact Statement What is already known on this subject? Miscarriages are considered to be the most common complication in pregnancy. Several possible causes of miscarriage have been considered, and the role of infections as one of those is confirmed, especially during the second trimester of pregnancy. The prevalence of HPV in conception products is still questionable. However, an HPV infection should not be ignored and its association with miscarriage must be considered. What the results of this study add? The present study reveals the presence of HPV in the foetal and maternal tissues of conception. What the implications are of these findings for clinical practice and/or further research? This issue deserves further investigation aiming to clarify the role of HPV in miscarriage cases; which are mainly related to the specific type and grade of tissues' abnormalities found co-topographically with a virus presence.

Investigation on Spontaneous Abortion and Human Papillomavirus Infection

“…The results of the present study are consistent with previous works reporting low HPV rates, 4–7%, in chorionic villi [ 24 , 65 , 66 ], including trophoblastic [ 66 , 67 ] and Hofbauer cells [ 51 ], which are the outer layer cells of the blastocyst and the placental macrophages, respectively [ 51 ]. Furthermore, despite never being demonstrated in vivo [ 68 , 69 , 70 ], in vitro studies have indicated that HPV could replicate in trophoblast cells [ 68 , 69 , 70 , 71 ], suggesting that this virus may not be strictly keratinocyte-specific [ 68 , 69 , 70 ].…”

“…However, the hypothesis that HPV can potentially infect pregnant females by crossing the placental barrier has been largely questioned. HPV DNA has been reported with high variable prevalence, 4–75%, in cord blood [ 66 , 72 , 73 , 74 ], amniotic fluids [ 75 , 76 , 77 , 78 ], cervical tissues [ 75 , 78 , 79 , 80 ], as well as fetal membranes, such as the placenta [ 51 , 66 , 75 , 78 , 79 , 81 , 82 ] and the decidua [ 24 , 83 ]. Other studies conducted on cord blood [ 75 ], amniotic fluids [ 75 , 77 , 84 ], and fetal membranes [ 79 ] do not support this evidence.…”

“…Such infectious agents include viruses which can negatively impact pregnancy, being linked to miscarriage and other outcomes such as stillbirth and preterm delivery [ 18 , 21 ]. A number of human viruses, including herpes simplex viruses 1 and 2, cytomegalovirus, dengue virus, zika virus, adenovirus, and adeno-associated virus can potentially infect the placenta, the trophoblast, and/or the cytotrophoblasts after viremia or an ascendant infection [ 18 , 22 , 23 , 24 , 25 , 26 , 27 ]. It is known that cytomegalovirus and herpes simplex viruses can cross the placental barrier, thereby resulting in either SA events or severe birth defects, such as microcephaly [ 21 ].…”

“…Previous studies on SA and HPV infection reported conflicting results [ 24 , 51 , 52 ]. Indeed, HPV DNA sequences have been detected with a large range of prevalence, from 4% to 75%, in SA samples and in 20–24% of specimens from females who underwent voluntary interruption of pregnancy (VI) [ 24 , 51 , 52 ]. In addition, the majority of these studies only reported qualitative data [ 24 , 51 , 52 ].…”

“…Indeed, HPV DNA sequences have been detected with a large range of prevalence, from 4% to 75%, in SA samples and in 20–24% of specimens from females who underwent voluntary interruption of pregnancy (VI) [ 24 , 51 , 52 ]. In addition, the majority of these studies only reported qualitative data [ 24 , 51 , 52 ]. These conflicting results have raised the question of whether HPV infection is linked to SA.…”