Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter January 13, 2022

To evaluate the role of placental human papilloma virus (HPV) infection as a risk factor for spontaneous preterm birth: a prospective case control study

  • Reetu Hooda , Neeru Baghla , Nisha Malik EMAIL logo and Samander Kaushik



i) To compare the placental human papilloma virus (HPV) deoxynucleic acid (DNA) status of preterm deliveries with full term deliveries and to identify high risk (HR) genotypes (HPV 16 and 18); and ii) To compare the perinatal outcomes of HPV positive with HPV negative pregnant women.


A case control study was carried out on 100 antenatal women with singleton live pregnancies admitted in labor ward of a tertiary care teaching hospital from April 2017 to March 2018. The two study groups were i) spontaneous preterm deliveries between 24 and 36 + 6 weeks (n=50) and ii) full term deliveries ≥37 weeks (n=50). The placental tissue was analysed for HPV DNA and HR HPV genotypes were detected by type specific primers. A comparative analysis of perinatal outcomes between HPV positive and negative women was done.


An overall placental tissue HPV prevalence of 12% (12/100) was observed in study cohort which was not significantly different between preterm and full term deliveries (16 vs. 8%, p=0.218). HPV 16 was significantly associated with preterm births (p=0.04). Both HPV affected and non-affected women were comparable in terms of mode of delivery and neonatal outcomes. However, a statistically significant association of preterm neonatal intensive care admissions with HR HPV 16 genotype was observed (p=0.04).


Spontaneous preterm births can be attributed to placental HPV infection, specifically HR HPV 16 genotype. This association identifies a potentially preventable cause of prematurity and its associated complications, in wake of availability of an effective vaccine.

Corresponding author: Dr. Nisha Malik, Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, Bilaspur, Himachal Pradesh, India, Phone: +91 7056544709, E-mail:


The authors acknowledge the patients who participated in the study.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The research has complied with all the relevant national regulations, institutional policies, and in accordance with the Helsinki declaration and has been approved by the Institutional Ethical Committee.


1. Goldenberg, RL, Culhane, JF, Iams, JD, Romero, R. Epidemiology and causes of preterm birth. Lancet 2008;371:75–84. in Google Scholar

2. Goldenberg, RL, Hauth, JC, Andrews, WW. Intrauterine infection and preterm delivery. N Engl J Med 2000;342:1500–7. in Google Scholar

3. Gibbs, RS, Romero, R, Hillier, SL, Eschenbach, DA, Sweet, RL. A review of premature birth and subclinical infection. Am J Obstet Gynecol 1992;166:1515–28. in Google Scholar

4. Goldenberg, RL, Andrews, WW, Goepfert, AR, Faye-Peterson, O, Cliver, SP, Carlo, WA, et al.. The Alabama Preterm Birth Study: umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants. Am J Obstet Gynecol 2008;198:43.e1–5. in Google Scholar

5. Leitich, H, Bodner-Adler, B, Brunbauer, M, Kaider, A, Egarter, C, Husslein, P. Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis. Am J Obstet Gynecol 2003;189:139–47. in Google Scholar

6. Huang, LW, Chao, SL, Chen, PH, Chou, HP. Multiple HPV genotypes in cervical carcinomas: improved DNA detection and typing in archival tissues. J Clin Virol 2004;29:271–6. in Google Scholar

7. Liu, Y, You, H, Chiriva-Internati, M, Korourian, S, Lowery, CL, Carey, MJ, et al.. Display of complete life cycle of human papillomavirus type 16 in cultured placental trophoblasts. Virology 2001;290:99–105. in Google Scholar

8. You, H, Liu, Y, Agrawal, N, Prasad, CK, Edwards, JL, Osborne, AF, et al.. Multiple human papillomavirus types replicate in 3A trophoblasts. Placenta 2008;29:30–8. in Google Scholar

9. You, H, Liu, Y, Agrawal, N, Prasad, CK, Chiriva-Internati, M, Lowery, CL, et al.. Infection, replication, and cytopathology of human papillomavirus type 31 in trophoblasts. Virology 2003;316:281–9. in Google Scholar

10. Ambuhl, LMM, Baandrup, U, Dypkaer, K, Blaakær, J, Uldbjerg, N, Sørensen, S. Human papilloma virus infection as a possible cause of spontaneous abortion and spontaneous preterm delivery. Infect Dis Obstet Gynecol 2016;2016:3086036. in Google Scholar

11. Gomez, LM, Ma, Y, Ho, C, McGrath, CM, Nelson, DB, Parry, S. Placental infection with human papillomavirus is associated with spontaneous preterm delivery. Hum Reprod 2008;23:709–15. in Google Scholar

12. Zuo, Z, Goel, S, Carter, JE. Association of cervical cytology and HPV DNA status during pregnancy with placental abnormalities and preterm birth. Am J Clin Pathol 2011;136:260–5. in Google Scholar

13. McDonnold, M, Dunn, H, Hester, A, Pacheco, LD, Hankins, GD, Saade, GR, et al.. High risk human papillomavirus at entry to prenatal care and risk of preeclampsia. Am J Obstet Gynecol 2014;210:138.e1–5. in Google Scholar

14. Cho, G, Min, KJ, Hong, HR, Kim, S, Hong, JH, Lee, JK, et al.. High-risk human papillomavirus infection is associated with premature rupture of membranes. BMC Pregnancy Childbirth 2013;13:173. in Google Scholar

15. Conde-Ferráez, L, Chan May Ade, A, Carillo-Martinez, JR, Ayora-Talavera, G, González-Losa Mdel, R. Human papillomavirus infection and spontaneous abortion: a case-control study performed in Mexico. Eur J Obstet Gynecol Reprod Biol 2013;170:468–73.10.1016/j.ejogrb.2013.07.002Search in Google Scholar PubMed

16. Trottier, H, Burchell, AN. Epidemiology of mucosal HPV infection and associated diseases. Public Health Genom 2009;12:291–307. in Google Scholar

17. Pandey, D, Solleti, V, Jain, G, Das, A, Prasada, KS, Acharya, S, et al.. Human papillomavirus (HPV) infection in early pregnancy: prevalence and implications. Infect Dis Obstet Gynecol 2019;2019:4376902. in Google Scholar

18. Amb€uhl, LMM, Leonhard, AK, Zakhary, CW, Jørgensen, A, Blaakær, J, Dybkær, K, et al.. Human papillomavirus infects placental trophoblast and hofbauer cells, but appears not to play a causal role in miscarriage and preterm labor. Acta Obstet Gynecol Scand 2017;96:1188–96.10.1111/aogs.13190Search in Google Scholar PubMed

19. Sarkola, ME, Grenman, SE, Rintala, MM, Syrj€anen, KJ, Syrj€anen, SM. Human papillomavirus in the placenta and umbilical cord blood. Acta Obstet Gynecol Scand 2008;87:1181–8. in Google Scholar

20. Kwon, J-Y, Romero, R, Mor, G. New insights into the relationship between viral infection and pregnancy complications. Am J Reprod Immunol 2014;71:387–90. in Google Scholar

21. Slatter, TL, Hung, NG, Clow, WM, Royds, JA, Devenish, CJ, Hung, NA. A clinicopathological study of episomal papillomavirus infection of the human placenta and pregnancy complications. Mod Pathol 2015;28:1369–82. in Google Scholar

22. Weyn, C, Thomas, D, Jani, J, Guizani, M, Donner, C, Van Rysselberge, M, et al.. Evidence of human papillomavirus in the placenta. J Infect Dis 2011;203:341–3. in Google Scholar

23. Huang, QT, Zhong, M, Gao, YF, Huang, LP, Huang, Q, Wang, W, et al.. Can HPV vaccine have other health benefits more than cancer prevention? A systematic review of association between cervical HPV infection and preterm birth. J Clin Virol 2014;61:321–8. in Google Scholar

24. Kaur, H, Schmidt, D, Remmenga, SW, Chen, B, Islam, KM, Watanabe-Galloway, S. Does papilloma virus affect pregnancy outcomes? Analysis of hospital data. Int J Women’s Health Wellness 2015;1:006. in Google Scholar

25. Hong, Y, Li, SQ, Hu, YL, Wang, ZQ. Survey of human papillomavirus types and their vertical transmission in pregnant women. BMC Infect Dis 2013;13:109. in Google Scholar

26. Koskimaa, HM, Waterboer, T, Pawlita, M, Grénman, S, Syrjänen, K, Syrjänen, S. Human papillomavirus genotypes present in the oral mucosa of newborns and their concordance with maternal cervical human papillomavirus genotypes. J Pediatr 2012;160:837–43. in Google Scholar

27. Lee, SM, Park, JS, Norwitz, ER, Koo, JN, Oh, IH, Park, JW, et al.. Risk of vertical transmission of human papillomavirus throughout pregnancy: a prospective study. PLoS One 2016;8:e66368. in Google Scholar

28. Rombaldi, RL, Serafini, EP, Mandelli, J, Zimmermann, E, Losquiavo, KP. Transplacental transmission of human papillomavirus. Virol J 2008;5:106. in Google Scholar

29. Lacour, D. Human pappilomavirus in infants: transmission, prevalence & persistence. J Pediatr Adolesc Gynecol 2012;25:93–7. in Google Scholar

30. Bonde, U, Joergensen, JS, Mogensen, O, Lamont, RF. The potential role of HPV vaccination in the prevention of infectious complications of pregnancy. Expert Rev Vaccines 2014;13:1307–16. in Google Scholar

Received: 2021-08-14
Accepted: 2021-12-18
Published Online: 2022-01-13
Published in Print: 2022-05-25

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 28.3.2023 from
Scroll Up Arrow