Human papillomavirus (HPV) vaccine is used to prevent sexually transmitted HPV infections and cervical cancers. People who are not vaccinated and contract HPV may experience future fertility problems associated with the infection. The vaccine currently approved by the FDA has been extensively tested and demonstrated to be both safe and effective with limited side effects. However, a recent research study has reignited historical public concern regarding HPV vaccination and the risk of primary ovarian insufficiency and infertility in women.
Human Papillomavirus - Illustration Credit: Liya Graphics / Shutterstock
What is HPV?
There are more than 100 HPV types that are transmitted sexually or via any skin-to-skin contact in the genital area. Low-risk HPVs mainly cause wart formation on the genitals, anus, mouth, and throat, whereas high-risk HPVs, especially HPV 16 and HPV 18, are associated with HPV-related cancers. These viruses mainly affect the squamous cells that form the inner surface of various genital organs, causing a variety of HPV-related cancers, such as cervical cancer, anal cancer, penile cancer, vaginal cancer, and vulvar cancer.
Cervical Cancer. Carcinoma is Malignant neoplasm arising from cells in the cervix uteri. Close-up of Human papillomavirus infection (HPV). cut-away view of the uterus and cervix that viewed from below. Image Credit: Designua / Shutterstock
How effective is HPV vaccination?
There is one HPV vaccine, Gardasil 9, which is currently approved for use in the United States and licenced in 2014. Previously an earlier version of Gardasil was licenced and another vaccine called Cervarix. Presently, FDA-approved HPV vaccination provides protection against infections caused by 2 low-risk and 7 high-risk HPVs. The vaccine consists of 2 shots that are given 6 to 12 months apart. According to the Centres for Disease Control and Prevention, HPV vaccine should be given to both boys and girls at the age of 11 or 12 years; however, the vaccine can also be given at the age of 9 years. The vaccine is most effective if it is given to someone before they become sexually active, whereas the vaccine may not be effective if given after getting the infection.
Pregnant women or people with moderate-to severe illness or severe allergies should not take the vaccine. The most common side-effects of HPV vaccination are pain, redness, or swelling at the injection site, nausea, headache, and dizziness.
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Does HPV vaccination cause infertility?
After the initial approval of HPV vaccine in 2006 by FDA, there was public concern regarding the safety of the vaccine with particular focus on whether it could cause primary ovarian insufficiency or premature menopause. Too add to this concern, in 2014 a medical case report from Australia was published reporting three cases of unexplained premature ovarian failure in adolescent girls where an adverse reaction to Gardasil (HPV4) vaccination was hypothesised as a possible explanation.
The author of a recent study analysing the National Health and Nutrition Examination Survey data on 8 million American women reported a correlation between women who had not had the vaccine and pregnancy. At least 60% of women who did not receive HPV vaccine becoming pregnant at least once during the survey period (2007 – 2014), whereas only 35% of women who received the vaccine became pregnant. While the authors concluded that in an age group of 25 – 29 years, HPV vaccinated women are less likely to become pregnant than women who are not vaccinated they have been roundly criticised for not taking into account the vaccine coverage in the respective age groups during the study period. Critics of the research have also pointed out that if the vaccine does affect fertility then a similar correlation would have been observed in other countries with good HPV vaccine coverage like Australia and the United Kingdom.
According to the data collected by the Vaccine Adverse Event Reporting System database, there were three reports of primary ovarian insufficiency out of 29 million doses of the Gardasil 9 HPV vaccine distributed in the United states between December 2014 and December 2017. All three were determined to be hearsay reports, meaning there was not enough information to confirm a medical diagnosis of primary ovarian insufficiency.
The authors of recent study looking at 200,000 young women who received various adolescent vaccines including HPV vaccine found no correlation between HPV vaccination and increased risk of primary ovarian insufficiency. The researchers calculated that among 58,871 young women who received HPV vaccine, only one woman showed the symptoms of primary ovarian insufficiency, suggesting that HPV vaccine is unlikely to affect fertility in young women.
Infection with HPV affects reproductive health and fertility in both men and women. Particularly in men, HPV negatively affects various sperm parameters, including motility. The virus can also increase trophoblastic cell death and decrease the implantation of trophoblastic cells in the uterus. These factors can potentially increase the risk of miscarriage, premature membrane rupture, or spontaneous premature delivery.
In women undergoing intrauterine insemination, infection with HPV is associated with a lower pregnancy rate. In these circumstances it can be considered that a vaccine designed to prevent HPV infection should improve someone’s chances of having a successful pregnancy.
A 2017 study, published in the journal Paediatric and Perinatal Epidemiology, showed little overall association between HPV vaccination and the chances of conceiving for men and women -- except among women with a history of sexually transmitted infections (STIs). STIs are associated with lower fertility, but vaccinated women with an STI history had about the same chance of becoming pregnant as unvaccinated women who had never had an STI.
"Our study found no adverse effects of HPV vaccination on fertility and indicated that it may, in fact, protect fertility among individuals who have had other STIs," says BUSPH doctoral student Kathryn McInerney, the study's lead author. "Our study should reassure those who are hesitant to vaccinate due to fertility concerns."
Researchers at Karolinska Institutet in Sweden and their Danish colleagues monitored HPV-vaccinated girls via patient data registries in order to examine the incidence of a wide range of diseases and thus determine if there were any serious adverse effects of the vaccine. Their results showed no significant increase of the examined diseases in the vaccinated girls relative to their unvaccinated peers. The 2103 study, published in the BMJ, included almost a million Swedish and Danish girls born between 1988 and 2000, and compared roughly 300,000 girls who had been HPV vaccinated with 700,000 who had not.
"You could see our study as part of a societal alarm system, and as such it did not alert us to any signs that HPV vaccination carries a risk of serious adverse events," says Dr Lisen Arnheim-Dahlström, associate professor at Karolinska Institutet's Department of Medical Epidemiology and Biostatistics.
There is currently no reliable evidence that links current or previous HPV vaccines with fertility-related problems. However, given the questions raised by the case reports and recent academic controversy around the way large systematic reviews of HPV vaccine safety are conducted, it is clear that further research is needed to conclusively establish whether there are any grounds to associate HPV vaccination with any reduction in male or female fertility.
It is important to remember that a lot of studies on vaccine outcome reported that HPV vaccine is both safe and highly effective in preventing cancer-causing infections.
Things that are important to remember about HPV vaccine
- Since its approval, HPV vaccine has significantly reduced the number of infections and HPV precancers.
- A rigorous safety testing before the approval of the vaccine, as well as close monitoring of more than 270 doses of HPV vaccine given globally since 2006 clearly indicate that the vaccine is very safe.
- HPV vaccine does not have any toxic/harmful ingredients. Although it contains aluminium, the amount is well within the safety level.
- Antibodies generated by HPV vaccine provide robust and long-lasting protection.
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- HPV Vaccine Facts. 2018. www.cancer.org/.../hpv-vaccine-facts-and-fears.html
- DeLong G. A lowered probability of pregnancy in females in the USA aged 25–29 who received a human papillomavirus vaccine injection. 2018. Journal of Toxicology and Environmental Health. https://www.tandfonline.com/doi/abs/10.1080/15287394.2018.1477640
- Naleway AL. Primary Ovarian Insufficiency and Adolescent Vaccination. 2018. Pediatrics. https://pediatrics.aappublications.org/content/142/3/e20180943
- Pereira N. Human Papillomavirus Infection, Infertility, and Assisted Reproductive Outcomes. 2015. Journal of Pathogens. https://www.ncbi.nlm.nih.gov/pubmed/26609434
- Little DT, Ward HRG Premature ovarian failure 3 years after menarche in a 16-year-old girl following human papillomavirus vaccination Case Reports 2012;2012:bcr2012006879. https://casereports.bmj.com/content/2012/bcr-2012-006879
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- Little DT, Ward HR. Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination: A Case Series Seen in General Practice. J Investig Med High Impact Case Rep. 2014;2(4):2324709614556129. Published 2014 Oct 28. doi:10.1177/2324709614556129, https://journals.sagepub.com/doi/10.1177/2324709614556129
- McInerney, K. A., Hatch, E. E., Wesselink, A. K., Mikkelsen, E. M., Rothman, K. J., Perkins, R. B. and Wise, L. A. (2017), The Effect of Vaccination Against Human Papillomavirus on Fecundability. Paediatr. Perinat. Epidemiol., 31: 531-536. doi:10.1111/ppe.12408, https://onlinelibrary.wiley.com/doi/10.1111/ppe.12408
- Autoimmune, neurological, and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark and Sweden: cohort study
BMJ 2013; 347 doi: https://doi.org/10.1136/bmj.f5906 (Published 09 October 2013), BMJ 2013;347:f5906, https://www.bmj.com/content/347/bmj.f5906