Myths and fake messages about human papillomavirus (HPV) vaccination: answers from the ESGO Prevention Committee
================================================================================================================

* Nadja Taumberger
* Elmar A Joura
* Marc Arbyn
* Maria Kyrgiou
* Jalid Sehouli
* Murat Gultekin

*   Cervical Cancer
*   Pathology
*   Gynecology

## Introduction

Vaccine hesitancy is a global challenge. This has become even more visible during the COVID-19 pandemic. In most European countries with a sufficient vaccine supply, public programs failed to achieve coverage of more than 80%. There are various reasons for this phenomenon: in addition to political positions and religious beliefs, many would rather rely on opinions than facts. These opinions are nurtured by myths, repeated over social media and the internet. Vaccines preventing infections, disease, and cancer caused by human papillomavirus (HPV) have been available for more than 15 years. After clinical trials provided data from tens of thousands of study participants, we now have the experience and observational data from hundreds of millions of vaccine doses distributed worldwide.1 These vaccines have demonstrated that they prevent not only HPV infections and pre-invasive disease, but also invasive cervical cancer.2–4

We have identified nine myths (summarized in Table 1) that we wish to discuss and dispel in this review article. This article will help support anyone who wants to give the best protection to children, adolescents, and adults by providing facts that can be used in discussions with individuals who might feel insecure after having heard various myths about HPV vaccination.

View this table:
[Table 1](http://ijgc.bmj.com/content/early/2022/07/11/ijgc-2022-003685/T1)

Table 1 
Summary of nine myths and fake messages about human papillomavirus vaccination

### Myth #1: PAP Smears and Annual Check-ups are Effective So There is No Need for Vaccination

The introduction of cervical cancer screening programs using cytology significantly reduced the incidence of cervical cancer, but these programs have limitations and do not make complete elimination feasible. However, screening programs only address cervical cancer and not all HPV-associated diseases. These programs are only a secondary prevention method since their goal is the early detection of pre-cancerous lesions. Primary prevention of cervical cancer—which means avoiding an HPV infection altogether—can be effectively accomplished by HPV vaccination. Furthermore, the implementation of screening programs has been shown to be challenging in low-income countries where, together with middle-income countries, approximately 85% of cervical cancer deaths occur.5

Based on our knowledge of the efficacy of HPV vaccination, the goal should be not only to detect HPV-related pre-cancerous lesions early but to avoid them totally. The elimination of cervical cancer will only be possible with the combination of vaccination and screening, preferably with HPV testing, including self-sampling for some women.6 HPV vaccination may also prevent other HPV-related malignancies that cannot be prevented through the detection and treatment of pre-invasive lesions, such as vaginal, vulvar, anal, penile, or oropharyngeal cancer.7

### Myth #2: HPV Vaccines are New So There are No Safety and Efficacy Data on the Long-Term Side Effects

The vaccines we use today have been thoroughly studied for decades now. The principle of these vaccines was described 30 years ago. The first vaccine trials with a monovalent HPV 16 vaccine—the very same component used in the currently available vaccine—started in 1997 and the results were published in 2002. The first vaccine to be licenced was the quadrivalent HPV 6/11/16/18 vaccine which became available in 2006, followed by the bivalent HPV 16/18 vaccine in 2007. Meanwhile, the second generation of vaccines with the nonavalent HPV vaccine has been available in Europe since 2016.8 To date we have more than 25 years of experience with these vaccines as well as observational data from hundreds of millions of distributed doses worldwide and several tens of thousands of study participants. The possible side effects are well documented and the safety of these vaccines has been confirmed by the World Health Organization (WHO), the US Centers for Disease Control and Prevention, and many other authorities.9 10

### Myth #3: HPV Vaccination Can Cause Ovarian Failure

The concern about ovarian failure is primarily based on different case reports, animal models, and analyses which evaluated pregnancy in populations vaccinated against HPV.11 12 Nevertheless, an evaluation in 2018 of nearly 20 000 women aged 11–34 years found no connection between adolescent vaccination and ovarian failure—only 1 of 46 patients with confirmed primary ovarian failure received an HPV vaccine.7 Furthermore, recent data from Denmark also showed no association between HPV vaccination and primary ovarian insufficiency among more than 950 000 Danish women and girls.13

### Myth #4: There are Several Vaccinations that Induced Severe Adverse Events Like Autoimmune Diseases and Death

There have been many studies to evaluate the reasons among parents for making the decision to not vaccinate their children against the HPV virus, with one of the most commonly reported reasons being “safety concerns”.14–16 In no small part because of media reports about a few cases of individuals who died shortly after—but without causality from—the HPV vaccination, the population has been sensitized with false and unproven information about the vaccine. To sum up the main safety concerns that have been reported, these involve fear of death after the vaccination, autoimmune disease and neurological syndromes,17 and premature ovarian insufficiency as discussed above.11 12 18–21

Addressing this myth, it must first be stated that numerous clinical trials and post-licensure studies have been published which reported a very good safety profile of the current approved and used HPV vaccines with no associations with serious adverse events. Summarizing the published recommendations of the US Food and Drug Administration and the European Medicines Agency, acute injection site reactions such as pain, swelling, and redness were higher in the vaccination group compared with the placebo recipients in pre-licensure clinical trials. Systematic adverse events such as headache and nausea were similar among both groups as well as autoimmune disease incidence. Concerning the deaths in a temporal context with HPV vaccination, none of these were considered to be vaccine-related according to the existing, published data based on clinical trials that included tens of thousands of participants.8 9 22–25 Furthermore, numerous studies have investigated the potential risk for autoimmune or neurological conditions which, among others, included more than 3 million adult females,26 nearly 1 million adolescent females27 and 600 000 boys,28 as well as a little more than 250 000 girls.29 Although minor risks have been reported for some conditions such as Reynaud’s disease, type 1 diabetes, vitiligo, or narcolepsy,26 28 30 no proven association with any of the conditions according to the investigated HPV vaccine could be made in those studies.26–29 31

### Myth #5: Children are Not Sexually Active So Why Vaccinate Them Against Something That Does Not Concern Them at This Age?

A question that often arises when discussing HPV vaccination at the recommended age of between 9 and 12 years is whether this is too young since sexual intercourse is not an issue at this age. One of the main parental concerns about earlier sexual activity and promiscuity (the final myth considered here), but also the concern about unnecessary vaccination against something that is not happening yet, is often mentioned.

The fact is that adolescents vaccinated under the age of 15 years showed much higher HPV antibody titers than their older peers. They had a better immune response. This, together with the results of clinical trials showing persistent high antibody titers after receiving two doses of HPV vaccination at younger ages, led to the recommendation of two doses in adolescents under the age of 15 years.32 Furthermore, one-dose regimes are currently being evaluated. The available data on the long-term effect shows almost complete effectiveness up to 14 years after vaccination. Also, the possibility of combining HPV vaccination with other recommended vaccines at this age by concomitant administration has been shown to lead to higher vaccine coverage in adolescents.33

Finally, we know that vaccination prior to the onset of sexual activity is most effective and that the age of first sexual contact differs among people, countries, and cultures. Although HPV is the most common sexually transmitted infection, non-sexual ways of contagion such as fomites, shared clothing, and horizontal as well as vertical transmission have been reported.34 35 Vaccination is designed to give long-term protection and, like other vaccines, it should not be administered close to a possible infection. The earlier you vaccinate teenagers the better, starting from the age of 9 years. You can never vaccinate too early but rather, unfortunately, sometimes you can vaccinate too late.

### Myth #6: Boys and Men Do Not Get Cervical Cancer So They Do Not Need a Vaccine

In addition to cervical cancer, HPV is linked to at least five other malignancies: vulvar, vaginal, anal, penile, and oropharyngeal cancer. The last three also occur in males. Thus, national and also many international vaccination regimes nowadays recommend HPV vaccination for girls and boys alike.36 37 As the overall genital HPV infection prevalence among men aged between 18 and 59 years in the United States was reported at approximately 45%, it is crucial to raise awareness about prevention of HPV-related cancers in young boys and men. Furthermore, men act as carriers for the virus and so the goal needs to be herd immunity of at least ideally 80% in girls-only vaccination and 60% in gender-neutral vaccination. Gender-neutral vaccination provides the best protection for all individuals regardless of gender and (future) sexual orientation and is a great opportunity to double the coverage. Also, male in addition to female vaccination will result in achieving cervical cancer elimination earlier.

### Myth #7: After the First Sexual Intercourse the Vaccine Does Not Work Anymore

One persistent and false myth is the missing efficacy and benefit of the HPV vaccination if given after the first sexual contact or intercourse. Randomized trials have demonstrated lower but still substantial and significant protection among young women regardless of prior HPV exposure against cervical pre-cancer compared with HPV-naïve women, in whom protection is excellent. However, in women vaccinated at an older age (>25 years), protection at the population level is low.22 A benefit of vaccinating women after treatment for cervical intraepithelial neoplasia is additional protection against recurrent disease compared with treatment without HPV vaccination.38 Nevertheless, high-level evidence from prospective randomized trials addressing this effect is needed and should be available soon, before a general recommendation for HPV vaccination adjuvant to treatment of pre-cancerous lesions can be given.39

### Myth #8: Natural HPV Infection Already Creates a Protective Antibody Response, So There is No Need for Vaccination

HPV reaches the basement membrane through fissures and infects basal cells. One characteristic of HPV infection is that the virus does not enter into the body’s circulation and does not cause local inflammation. Thus, an antibody response is low to absent. Studies have shown that recurrent, natural HPV infections were seen equally in women after years of follow-up, regardless of the type-specific serological status. In a meta-analysis of 14 eligible studies that included >24 000 individuals from 18 countries that examined HPV natural immunity, the authors observed moderate protection against subsequent infection in female subjects of the order of 30%, but not in male subjects.40 The natural immune response is insufficient to control for new infections and is far lower when compared with the high levels of seroresponse and the high efficacy observed against persistent infections after HPV vaccination.41

### Myth #9: HPV Vaccination Increases Risky Sexual Behavior and Promiscuity

A myth that repeatedly arises in the context of HPV vaccination is possible sexual disinhibition in adolescents. This can lead to lower vaccination rates in earlier years because of parents’ concerns about possible promiscuity and increased risky sexual behavior.42 43 Because of this reported issue, two systematic reviews have been performed that address this issue. These reviews reported an increased need for precise information about HPV-related diseases and HPV vaccination as well as lower rates of sexual intercourse without condoms and without contraception in the cohort of vaccinated adolescents.44 45 Furthermore, the rate of chlamydia was higher in the unvaccinated cohort.45 To date, several studies have addressed this question and found no evidence for an impact on sexual behavior in adolescents after receiving HPV vaccination compared with an unvaccinated cohort.43 46–48

Rysavy et al48 also highlighted the need for early vaccination as their investigated cohort suggested sexual activity at a young age. Real-world experience has clearly demonstrated that early vaccination is more effective than vaccination after the age of 15–17 years.1 3 Finally, the necessity of better information and education of adolescents and their parents regarding HPV-related diseases and HPV vaccination to resolve all doubts is needed.49 The aforementioned findings strongly suggest that there is no evidence that HPV vaccination increases promiscuity and that these concerns should not deter parents from giving consent for their children to be vaccinated at a young age.

## Conclusions

HPV vaccines are highly effective in girls and young women and likely also in boys and young men, in particular among those individuals that are HPV DNA-negative at the time of HPV vaccination. Moreover, licenced HPV vaccines have demonstrated balanced occurrence of severe adverse effects through trials and real-life surveillance activities. There is a need to continue to publicize, clearly communicate, and disseminate these data to further reduce HPV-related pre-invasive and invasive disease.

## Ethics statements

### Patient consent for publication

Not applicable.

### Ethics approval

Not applicable.

## Acknowledgments

We acknowledge the work and effort of all co-authors and participating colleagues.

## Footnotes

*   Twitter @NadjaTaumberger

*   Collaborators ESGO Prevention Committee: NT, EAJ, MA, MK, JS, MG.

*   Contributors All the authors participated in the conception, writing, and reviewing of the final version of this article.

*   Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

*   Competing interests MA and MG were supported by the Horizon 2020 Framework Programme for Research and Innovation of the European Commission through the RISCC Network (Grant No. 847845).

*   Provenance and peer review Not commissioned; internally peer reviewed.

*   Received May 15, 2022.
*   Accepted May 20, 2022.


*   © IGCS and ESGO 2022. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.

[http://creativecommons.org/licenses/by-nc/4.0/](http://creativecommons.org/licenses/by-nc/4.0/)
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non-commercial. See: [http://creativecommons.org/licenses/by-nc/4.0/](http://creativecommons.org/licenses/by-nc/4.0/).

## References

1.  Drolet M, Bénard Élodie, Pérez N, et al. Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis. Lancet 2019;394:497–509.[doi:10.1016/S0140-6736(19)30298-3](http://dx.doi.org/10.1016/S0140-6736(19)30298-3)pmid:http://www.ncbi.nlm.nih.gov/pubmed/31255301
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1016/S0140-6736(19)30298-3&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=31255301&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

2.  Falcaro M, Castañon A, Ndlela B, et al. The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study. Lancet 2021;398:2084–92.[doi:10.1016/S0140-6736(21)02178-4](http://dx.doi.org/10.1016/S0140-6736(21)02178-4)pmid:http://www.ncbi.nlm.nih.gov/pubmed/34741816
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1016/S0140-6736(21)02178-4&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

3.  Lei J, Ploner A, Elfström KM, et al. HPV vaccination and the risk of invasive cervical cancer. N Engl J Med 2020;383:1340–8.[doi:10.1056/NEJMoa1917338](http://dx.doi.org/10.1056/NEJMoa1917338)pmid:http://www.ncbi.nlm.nih.gov/pubmed/32997908
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1056/NEJMoa1917338&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

4.  Kjaer SK, Dehlendorff C, Belmonte F, et al. Real-world effectiveness of human papillomavirus vaccination against cervical cancer. J Natl Cancer Inst 2021;113:1329–35.[doi:10.1093/jnci/djab080](http://dx.doi.org/10.1093/jnci/djab080)pmid:http://www.ncbi.nlm.nih.gov/pubmed/33876216
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

5.  Arbyn M, Weiderpass E, Bruni L, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health 2020;8:e191–203.[doi:10.1016/S2214-109X(19)30482-6](http://dx.doi.org/10.1016/S2214-109X(19)30482-6)pmid:http://www.ncbi.nlm.nih.gov/pubmed/31812369
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1016/S2214-109X(19)30482-6&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

6.  Petry K-U, Bollaerts K, Bonanni P, et al. Estimation of the individual residual risk of cervical cancer after vaccination with the nonavalent HPV vaccine. Hum Vaccin Immunother 2018;14:1800–6.[doi:10.1080/21645515.2018.1450125](http://dx.doi.org/10.1080/21645515.2018.1450125)pmid:http://www.ncbi.nlm.nih.gov/pubmed/29553886
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

7.  Bednarczyk RA. Addressing HPV vaccine myths: practical information for healthcare providers. Hum Vaccin Immunother 2019;15:1628–38.[doi:10.1080/21645515.2019.1565267](http://dx.doi.org/10.1080/21645515.2019.1565267)pmid:http://www.ncbi.nlm.nih.gov/pubmed/30676241
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

8.  Joura EA, Giuliano AR, Iversen O-E, et al. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med 2015;372:711–23.[doi:10.1056/NEJMoa1405044](http://dx.doi.org/10.1056/NEJMoa1405044)pmid:http://www.ncbi.nlm.nih.gov/pubmed/25693011
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1056/NEJMoa1405044&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=25693011&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

9.  Moreira ED, Block SL, Ferris D, et al. Safety profile of the 9-valent HPV vaccine: a combined analysis of 7 phase III clinical trials. Pediatrics 2016;138:e20154387.[doi:10.1542/peds.2015-4387](http://dx.doi.org/10.1542/peds.2015-4387)pmid:http://www.ncbi.nlm.nih.gov/pubmed/27422279
    
    [Abstract/FREE Full Text](http://ijgc.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTA6InBlZGlhdHJpY3MiO3M6NToicmVzaWQiO3M6MTU6IjEzOC8yL2UyMDE1NDM4NyI7czo0OiJhdG9tIjtzOjQ0OiIvaWpnYy9lYXJseS8yMDIyLzA3LzExL2lqZ2MtMjAyMi0wMDM2ODUuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

10. Centers for Disease Control and Prevention (CDC). HPV vaccine safety and effectiveness data, 2021. Available: [https://www.cdc.gov/hpv/hcp/vaccine-safety-data.html](https://www.cdc.gov/hpv/hcp/vaccine-safety-data.html)
    
    

11. Geier DA, Geier MR. Quadrivalent human papillomavirus vaccine and autoimmune adverse events: a case-control assessment of the vaccine adverse event reporting system (VAERS) database. Immunol Res 2017;65:46–54.[doi:10.1007/s12026-016-8815-9](http://dx.doi.org/10.1007/s12026-016-8815-9)pmid:http://www.ncbi.nlm.nih.gov/pubmed/27406735
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

12. Pellegrino P, Carnovale C, Perrone V, et al. On the association between human papillomavirus vaccine and primary ovarian failure. Am J Reprod Immunol 2014;71:293–4.[doi:10.1111/aji.12190](http://dx.doi.org/10.1111/aji.12190)pmid:http://www.ncbi.nlm.nih.gov/pubmed/24372880
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

13. Hviid A, Myrup Thiesson E. Association between human papillomavirus vaccination and primary ovarian insufficiency in a nationwide cohort. JAMA Netw Open 2021;4:e2120391.[doi:10.1001/jamanetworkopen.2021.20391](http://dx.doi.org/10.1001/jamanetworkopen.2021.20391)pmid:http://www.ncbi.nlm.nih.gov/pubmed/34436612
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

14. Sonawane K, Zhu Y, Montealegre JR, et al. Parental intent to initiate and complete the human papillomavirus vaccine series in the USA: a nationwide, cross-sectional survey. Lancet Public Health 2020;5:e484–92.[doi:10.1016/S2468-2667(20)30139-0](http://dx.doi.org/10.1016/S2468-2667(20)30139-0)pmid:http://www.ncbi.nlm.nih.gov/pubmed/32707126
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

15. Thompson EL, Rosen BL, Vamos CA, et al. Human papillomavirus vaccination: what are the reasons for nonvaccination among U.S. adolescents? J Adolesc Health 2017;61:288–93.[doi:10.1016/j.jadohealth.2017.05.015](http://dx.doi.org/10.1016/j.jadohealth.2017.05.015)
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1016/j.jadohealth.2017.05.015&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

16. Chido-Amajuoyi OG, Talluri R, Shete SS, et al. Safety concerns or adverse effects as the main reason for human papillomavirus vaccine refusal: National Immunization Survey–Teen, 2008 to 2019. JAMA Pediatr 2021;175:1074-1076.[doi:10.1001/jamapediatrics.2021.1585](http://dx.doi.org/10.1001/jamapediatrics.2021.1585)pmid:http://www.ncbi.nlm.nih.gov/pubmed/34180965
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

17. Segal Y, Dahan S, Calabrò M, et al. HPV and systemic lupus erythematosus: a mosaic of potential crossreactions. Immunol Res 2017;65:564–71.[doi:10.1007/s12026-016-8890-y](http://dx.doi.org/10.1007/s12026-016-8890-y)pmid:http://www.ncbi.nlm.nih.gov/pubmed/28111707
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

18. Gruber N, Shoenfeld Y. A link between human papilloma virus vaccination and primary ovarian insufficiency: current analysis. Curr Opin Obstet Gynecol 2015;27:265–70.[doi:10.1097/GCO.0000000000000183](http://dx.doi.org/10.1097/GCO.0000000000000183)pmid:http://www.ncbi.nlm.nih.gov/pubmed/26125978
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=26125978&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

19. Little DT, Ward HRG. Premature ovarian failure 3 years after menarche in a 16-year-old girl following human papillomavirus vaccination. BMJ Case Rep 2012;2012. doi:[doi:10.1136/bcr-2012-006879](http://dx.doi.org/10.1136/bcr-2012-006879). [Epub ahead of print: 30 Sep 2012].pmid:http://www.ncbi.nlm.nih.gov/pubmed/23035167
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

20. Little DT, Ward HRG. Adolescent premature ovarian insufficiency following human papillomavirus vaccination: a case series seen in general practice. J Investig Med High Impact Case Rep 2014;2.[doi:10.1177/2324709614556129](http://dx.doi.org/10.1177/2324709614556129)pmid:http://www.ncbi.nlm.nih.gov/pubmed/26425627
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

21. Colafrancesco S, Perricone C, Tomljenovic L, et al. Human papilloma virus vaccine and primary ovarian failure: another facet of the autoimmune/inflammatory syndrome induced by adjuvants. Am J Reprod Immunol 2013;70:309–16.[doi:10.1111/aji.12151](http://dx.doi.org/10.1111/aji.12151)pmid:http://www.ncbi.nlm.nih.gov/pubmed/23902317
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1111/aji.12151&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=23902317&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

22. Arbyn M, Xu L, Simoens C, et al. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev 2018;5:CD009069.[doi:10.1002/14651858.CD009069.pub3](http://dx.doi.org/10.1002/14651858.CD009069.pub3)pmid:http://www.ncbi.nlm.nih.gov/pubmed/29740819
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1002/14651858.CD009069.pub3&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=29740819&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

23. Huh WK, Joura EA, Giuliano AR, et al. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16–26 years: a randomised, double-blind trial.Lancet 2017;390:2143–59.[doi:10.1016/S0140-6736(17)31821-4](http://dx.doi.org/10.1016/S0140-6736(17)31821-4)
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1016/S0140-6736(17)31821-4&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=28886907&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

24. Vorsters A, Arbyn M, Baay M, et al. Overcoming barriers in HPV vaccination and screening programs. Papillomavirus Res 2017;4:45–53.[doi:10.1016/j.pvr.2017.07.001](http://dx.doi.org/10.1016/j.pvr.2017.07.001)pmid:http://www.ncbi.nlm.nih.gov/pubmed/29179869
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

25. McCarthy NL, Gee J, Sukumaran L, et al. Vaccination and 30-day mortality risk in children, adolescents, and young adults. Pediatrics 2016;137:e20152970 [https://pediatrics.aappublications.org/content/137/3/e20152970](https://pediatrics.aappublications.org/content/137/3/e20152970)[doi:https://doi.org/10.1542/peds.2015-2970](http://dx.doi.org/https://doi.org/10.1542/peds.2015-2970)
    
    

26. Hviid A, Svanström H, Scheller NM, et al. Human papillomavirus vaccination of adult women and risk of autoimmune and neurological diseases. J Intern Med 2018;283:154–65.[doi:10.1111/joim.12694](http://dx.doi.org/10.1111/joim.12694)pmid:http://www.ncbi.nlm.nih.gov/pubmed/29044769
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1111/joim.12694&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=29044769&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

27. Arnheim-Dahlström L, Pasternak B, Svanström H, et al. 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:10.1136/bmj.f5906](http://dx.doi.org/10.1136/bmj.f5906)pmid:http://www.ncbi.nlm.nih.gov/pubmed/24108159
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

28. Frisch M, Besson A, Clemmensen KKB, et al. Quadrivalent human papillomavirus vaccination in boys and risk of autoimmune diseases, neurological diseases and venous thromboembolism. Int J Epidemiol 2018;47:634–41.[doi:10.1093/ije/dyx273](http://dx.doi.org/10.1093/ije/dyx273)pmid:http://www.ncbi.nlm.nih.gov/pubmed/29425361
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

29. Liu EY, Smith LM, Ellis AK, et al. Quadrivalent human papillomavirus vaccination in girls and the risk of autoimmune disorders: the Ontario Grade 8 HPV Vaccine Cohort Study. Can Med Assoc J 2018;190:E648–55.[doi:10.1503/cmaj.170871](http://dx.doi.org/10.1503/cmaj.170871)pmid:http://www.ncbi.nlm.nih.gov/pubmed/29807937
    
    [Abstract/FREE Full Text](http://ijgc.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czoxMToiMTkwLzIxL0U2NDgiO3M6NDoiYXRvbSI7czo0NDoiL2lqZ2MvZWFybHkvMjAyMi8wNy8xMS9pamdjLTIwMjItMDAzNjg1LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

30. Klein NP, Goddard K, Lewis E, et al. Long term risk of developing type 1 diabetes after HPV vaccination in males and females. Vaccine 2019;37:1938–44.[doi:10.1016/j.vaccine.2019.02.051](http://dx.doi.org/10.1016/j.vaccine.2019.02.051)pmid:http://www.ncbi.nlm.nih.gov/pubmed/30827738
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

31. Chao C, Klein NP, Velicer CM, et al. Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med 2012;271:193–203.[doi:10.1111/j.1365-2796.2011.02467.x](http://dx.doi.org/10.1111/j.1365-2796.2011.02467.x)pmid:http://www.ncbi.nlm.nih.gov/pubmed/21973261
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1111/j.1365-2796.2011.02467.x&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=21973261&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

32. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination — updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2016;65:1405–8.[doi:10.15585/mmwr.mm6549a5](http://dx.doi.org/10.15585/mmwr.mm6549a5)
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.15585/mmwr.mm6549a5&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=27977643&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

33. Stokley S, Jeyarajah J, Yankey D, et al. Human papillomavirus vaccination coverage among adolescents, 2007-2013, and postlicensure vaccine safety monitoring, 2006-2014--United States. MMWR Morb Mortal Wkly Rep 2014;63:620–4.pmid:http://www.ncbi.nlm.nih.gov/pubmed/25055185
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=25055185&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

34. Liu Z, Rashid T, Nyitray AG. Penises not required: a systematic review of the potential for human papillomavirus horizontal transmission that is non-sexual or does not include penile penetration. Sex Health 2016;13:10–21.[doi:10.1071/SH15089](http://dx.doi.org/10.1071/SH15089)
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=26433493&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

35. Petca A, Borislavschi A, Zvanca M. Non-sexual HPV transmission and role of vaccination for a better future (Review). Exp Ther Med 2020;20:1.[doi:10.3892/etm.2020.9316](http://dx.doi.org/10.3892/etm.2020.9316)
    
    

36. European Centre for Disease Prevention and Control. Guidance on HPV vaccination in EU countries: focus on boys, people living with HIV and 9 valent HPV vaccine introduction. [Internet]. LU: Publications Office, 2021. Available: [https://data.europa.eu/doi/10.2900/71487](https://data.europa.eu/doi/10.2900/71487)
    
    

37. Bonanni P, Faivre P, Lopalco PL, et al. The status of human papillomavirus vaccination recommendation, funding, and coverage in WHO Europe countries (2018–2019). Expert Rev Vaccines 2020;19:1073–83.[doi:10.1080/14760584.2020.1858057](http://dx.doi.org/10.1080/14760584.2020.1858057)pmid:http://www.ncbi.nlm.nih.gov/pubmed/33267673
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

38. Jentschke M, Kampers J, Becker J, et al. Prophylactic HPV vaccination after conization: a systematic review and meta-analysis. Vaccine 2020;38:6402–9.[doi:10.1016/j.vaccine.2020.07.055](http://dx.doi.org/10.1016/j.vaccine.2020.07.055)pmid:http://www.ncbi.nlm.nih.gov/pubmed/32762871
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

39. Ralf van de Laar.. Trial NL7938: VACCIN Study: Adjuvant VACcination against HPV in surgical treatment of CIN lesions, a randomised controlled trial [Internet]. Netherlands Trial Register. 2019 [cited 2022 Mar 16]. Available: [https://www.trialregister.nl/trial/7938](https://www.trialregister.nl/trial/7938)
    
    

40. Beachler DC, Jenkins G, Safaeian M, et al. Natural acquired immunity against subsequent genital human papillomavirus infection: a systematic review and meta-analysis. J Infect Dis 2016;213:1444–54.[doi:10.1093/infdis/jiv753](http://dx.doi.org/10.1093/infdis/jiv753)pmid:http://www.ncbi.nlm.nih.gov/pubmed/26690341
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1093/infdis/jiv753&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=26690341&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

41. de Sanjosé S, Brotons M, Pavón MA. The natural history of human papillomavirus infection. Best Pract Res Clin Obstet Gynaecol 2018;47:2–13.[doi:10.1016/j.bpobgyn.2017.08.015](http://dx.doi.org/10.1016/j.bpobgyn.2017.08.015)pmid:http://www.ncbi.nlm.nih.gov/pubmed/28964706
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1016/j.bpobgyn.2017.08.015&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

42. Hilton S, Hunt K, Langan M, et al. Newsprint media representations of the introduction of the HPV vaccination programme for cervical cancer prevention in the UK (2005–2008). Soc Sci Med 2010;70:942–50.[doi:10.1016/j.socscimed.2009.11.027](http://dx.doi.org/10.1016/j.socscimed.2009.11.027)pmid:http://www.ncbi.nlm.nih.gov/pubmed/20064682
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1016/j.socscimed.2009.11.027&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=20064682&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

43. Forster AS, Marlow LAV, Stephenson J, et al. Human papillomavirus vaccination and sexual behaviour: cross-sectional and longitudinal surveys conducted in England. Vaccine 2012;30:4939–44.[doi:10.1016/j.vaccine.2012.05.053](http://dx.doi.org/10.1016/j.vaccine.2012.05.053)pmid:http://www.ncbi.nlm.nih.gov/pubmed/22664223
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1016/j.vaccine.2012.05.053&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=22664223&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 
    
    [Web of Science](http://ijgc.bmj.com/lookup/external-ref?access_num=000306621900006&link_type=ISI) 

44. Coles VAH, Patel AS, Allen FL, et al. The association of human papillomavirus vaccination with sexual behaviours and human papillomavirus knowledge: a systematic review. Int J STD AIDS 2015;26:777–88 [https://journals-1sagepub-1com-10013b5t307e1.han.medunigraz.at/doi/10.1177/0956462414554629](https://journals-1sagepub-1com-10013b5t307e1.han.medunigraz.at/doi/10.1177/0956462414554629)[doi:10.1177/0956462414554629](http://dx.doi.org/10.1177/0956462414554629)
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1177/0956462414554629&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=25300588&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

45. Kasting ML, Shapiro GK, Rosberger Z, et al. Tempest in a teapot: a systematic review of HPV vaccination and risk compensation research. Hum Vaccin Immunother 2016;12:1435–50.[doi:10.1080/21645515.2016.1141158](http://dx.doi.org/10.1080/21645515.2016.1141158)pmid:http://www.ncbi.nlm.nih.gov/pubmed/26864126
    
    [CrossRef](http://ijgc.bmj.com/lookup/external-ref?access_num=10.1080/21645515.2016.1141158&link_type=DOI) 
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=26864126&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

46. Smith LM, Kaufman JS, Strumpf EC, et al. Effect of human papillomavirus (HPV) vaccination on clinical indicators of sexual behaviour among adolescent girls: the Ontario Grade 8 HPV Vaccine Cohort Study. Can Med Assoc J 2015;187:E74–81.[doi:10.1503/cmaj.140900](http://dx.doi.org/10.1503/cmaj.140900)
    
    [Abstract/FREE Full Text](http://ijgc.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo5OiIxODcvMi9FNzQiO3M6NDoiYXRvbSI7czo0NDoiL2lqZ2MvZWFybHkvMjAyMi8wNy8xMS9pamdjLTIwMjItMDAzNjg1LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

47. Bednarczyk RA, Davis R, Ault K, et al. Sexual activity-related outcomes after human papillomavirus vaccination of 11- to 12-year-olds. Pediatrics 2012;130:798–805.[doi:10.1542/peds.2012-1516](http://dx.doi.org/10.1542/peds.2012-1516)pmid:http://www.ncbi.nlm.nih.gov/pubmed/23071201
    
    [Abstract/FREE Full Text](http://ijgc.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTA6InBlZGlhdHJpY3MiO3M6NToicmVzaWQiO3M6OToiMTMwLzUvNzk4IjtzOjQ6ImF0b20iO3M6NDQ6Ii9pamdjL2Vhcmx5LzIwMjIvMDcvMTEvaWpnYy0yMDIyLTAwMzY4NS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

48. Rysavy MB, Kresowik JDK, Liu D, et al. Human papillomavirus vaccination and sexual behavior in young women. J Pediatr Adolesc Gynecol 2014;27:67–71.[doi:10.1016/j.jpag.2013.08.009](http://dx.doi.org/10.1016/j.jpag.2013.08.009)pmid:http://www.ncbi.nlm.nih.gov/pubmed/24405635
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom) 

49. Mullins TLK, Zimet GD, Rosenthal SL, et al. Adolescent perceptions of risk and need for safer sexual behaviors after first human papillomavirus vaccination. Arch Pediatr Adolesc Med 2012;166.[doi:10.1001/archpediatrics.2011.186](http://dx.doi.org/10.1001/archpediatrics.2011.186)pmid:http://www.ncbi.nlm.nih.gov/pubmed/22213755
    
    [PubMed](http://ijgc.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fijgc%2Fearly%2F2022%2F07%2F11%2Fijgc-2022-003685.atom)