Most people have probably heard of HPV (Human Papilloma Virus), a group of about 150 viruses, categorized in types. Certain types of HPV are among the most common sexually transmitted viruses. While an estimated 90% of all infections are spontaneously cleared by the human body, the other 10% can influence your health. Some HPV types are relatively innocent and can cause warts (‘papillomas’, hence the name), while others can lead to various types of cancer, of which the best known is probably cervical cancer.
Many people are already familiar with the Pap smear tests used in government screening campaigns and the vaccination of teenage girls against certain types of HPV, but there is more to this group of viruses than meets the eye. Over the last years, more and more researchers have started delving into the relationship between HPV and pregnancy. This involves questions such as: does a maternal HPV infection influence the course and outcome of a pregnancy? Can an infected mother transmit the virus to her unborn child? And if so, how, and will it affect the child’s health?
Preterm Birth & Membranes
According to Australian researchers, women who have had a positive Pap smear (which points to a probable HPV infection), are more likely to have a baby with Intrauterine Growth Restriction (IUGR). They base their conclusion on an analysis of Pap smear records of almost 32.000 women who, within two years of testing, gave birth to a life singleton. After adjusting for other relevant risk factors, it was found that the babies were 20% more likely to be small for gestational age (SGA) and 50% more likely to have very low birth weight (VLBW) than those born from mothers with a negative smear.
In another recent study, an association was found between maternal infection with HPV and an increased risk of Preterm Premature Rapture of Membranes (PPROM), which, in its turn, is associated with preterm delivery. And even though the authors of a 2016 literature review warned of the limited number of available studies and possible methodological flaws, they did report “an association between spontaneous abortion, spontaneous preterm delivery, and the presence of HPV in both the cervix and the placenta”.
While certain types of HPV are certainly, as most people will know, sexually transmittable, Koskimaa et al. point out that there is a growing body of research suggesting that the virus might also be transmitted in other ways. HPV was for instance detected in the oral and genital mucosa of newborns and sexually inactive children, as well as in the foreskins of asymptomatic healthy infants and children.
As Syrjänen and others point out, infected mothers may be a source of primary infection. In a 2013 literature analysis, Belgian researchers concluded that children of HPV positive mothers run a higher risk of contracting HPV than those whose mothers were HPV negative. According to Koskimaa et al., researchers have reported vertical transmission rates varying from 18.2 to 53.3% in mother-baby pairs. Nevertheless, vertical transmission is certainly not the only possible transmission route. Horizontal transmission and autoinoculation have also been suggested. In any case, establishing the HPV positive status of a child still leaves us with the question whether it was truly infected or passively contaminated.
If vertical transmission occurs, the question remains when exactly: at fertilization, prenatally or perinatally? The scientific debate is ongoing, although some studies point towards prenatal transmission. HPV DNA was, among other sites, found in cord blood, amniotic fluid, foetal membranes and placental trophoblastic cells. In this respect, Koskimaa et al. put a light on the possible role of the placenta (which may act as a place where maternal microbes interact with the fetal immune system), in line with a previous study in which the possibility of transmission through the placenta was proposed.
Finally, there is the question with regard to risks for the child once the virus has been transmitted. One possible complication is the development of laryngeal papillomatosis due to HPV 6 or 11 (typically between the age of 2 to 5 years old), which is called Juvenile Onset Recurrent Respiratory Papillomatosis (JORRP). This is a very rare, but potentially life threatening condition that reportedly occurs only 1 to 4 times per 100.000 births. Other conditions potentially caused by HPV infection include anogenital warts. An infection with HPV 6, 11 or 16 may also lead to conjunctival papilloma.
HPV regularly makes headlines, especially where prevention is concerned. In this field, an interesting development is taking place. For years, the above mentioned Pap smear test (cytology test) was the most important instrument in many cervical cancer screening programs. While it has been successful, the focus is gradually shifting towards screening a sample of cells from the genitals or cervix for HPV DNA, a method considered more effective.
Besides, it is encouraging to see that the attention for the role of the virus in the development of pregnancies and (unborn) children is growing. Given the possible relevance for maternal and fetal health, we are looking forward to the new findings that can be expected.
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Ambühl, L. et al. (2016) Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery. Infectious Diseases in Obstetrics and Gynecology. See: http://dx.doi.org/10.1155/2016/3086036
Cotton-Caballero, A. et al. (2017) Maternal Human Papillomavirus Infection Increases the Risk of Premature Rupture of Membranes. Obstetrics & Gynecology. See: http://dx.doi.org/10.1097/01.AOG.0000514690.21416.7c
Ford, J.H., Li, M., Scheil, W. & Roder, D. (2017) Human papillomavirus infection and intrauterine growth restriction: a data-linkage study. The Journal of Maternal-Fetal & Neonatal Medicine. See: http://dx.doi.org/10.1080/14767058.2017.1378330
Koskimaa, H.-M. et al. (2011) Human Papillomavirus Genotypes Present in the Oral Mucosa of Newborns and their Concordance with Maternal Cervical Human Papillomavirus Genotypes. The Journal of pediatrics 160: 837-843. See: http://dx.doi.org/10.1016/j.jpeds.2011.10.027
Koskimaa, H.-M. Et al. (2017) The presence of human papillomavirus (HPV) in placenta and/or cord blood might result in Th2 polarization. European Journal of Clinical Microbiology & Infectious Diseases 36(8): 1491-1503. See: https://link.springer.com/article/10.1007/s10096-017-2958-z
Lee, B. et al. (2017) HPV prevalence in the foreskins of asymptomatic healthy infants and children: Systematic review and meta-analysis. Sci Rep 7: 7050. See: http://dx.doi.org/10.1038/s41598-017-07506-z
Merckx, M. et al. (2013). Transmission of carcinogenic human papillomavirus types from mother to child: a meta-analysis of published studies. European Journal of Cancer Prevention 22: 277-285. See: http://icrh.org/sites/default/files/2013_15.pdf
Rintala, M. et al. (2005) High-Risk Types of Human Papillomavirus (HPV) DNA in Oral and Genital Mucosa of Infants during Their First 3 Years of Life: Experience from the Finnish HPV Family Study. Clinical Infectious Diseases. See: https://doi.org/10.1086/498114
Sarkola, M.E. et al. (2008) Human papillomavirus in the placenta and umbilical cord blood. AOGS 87(11): 1181-1188. See: http://dx.doi.org/10.1080/00016340802468308
Singhal, P., Naswa, S. & Marfatia, Y. (2009) Pregnancy and sexually transmitted viral infections. Indian J Sex Trans Dis 30(2): 71-78. See: http://dx.doi.org/10.4103/0253-7184.62761
Syrjänen S. (2010) Current concepts on human papillomavirus infections in children. APMIS 118: 494–509. See: http://dx.doi.org/10.1111/j.1600-0463.2010.02620.x
Trottier, H. et al. (2016) Human papillomavirus (HPV) perinatal transmission and risk of HPV persistence among children: Design, methods and preliminary results of the HERITAGE study. Papillomavirus Research 2: 145-152. See: https://doi.org/10.1016/j.pvr.2016.07.001
WHO/IARC (2007) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 90 - Human Papillomaviruses. See: http://monographs.iarc.fr/ENG/Monographs/vol90/mono90.pdf
Photo 1: By Blausen Medical Communications, Inc. - Donated via OTRS, see ticket for details, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=27639313
Photo 2: CCBY Lee Health, Detecting Vaginal Cancer. See: https://vimeo.com/235194595
Photo 3: CCBY Cancer Research UK/Wikimedia Commons. See: https://commons.wikimedia.org/wiki/File:Diagram_showing_the_transformation_zone_on_the_cervix_CRUK_375.svg