In my first blog post on connections between cervical cancer risk and systemic lupus erythematosus, I suggested that, since high-risk strains of sexually-transmitted human papillomavirus (HPV) cause most cases of cervical cancer, young women with SLE should ask their gynecologists about the advisability of getting the HPV vaccine.
Since there have been concerns about vaccines causing autoimmunity this raises a legitimate question: Could the HPV vaccines Gardasil, Gardasil 9, or Cervarix trigger another autoimmune disease?
A number of recent studies, including a large population study from Sweden published online July 31 in the Journal of Internal Medicine, provide some reassurance.
The study examined medical records for all 70,265 girls and women ages 10 to 30 in Sweden diagnosed with at least one of 49 autoimmune diseases between 2006 and 2010, 16% of whom had received at least one dose of HPV vaccine. The researchers found no increase in new-onset autoimmune disease in the six months after immunization.1 In fact, there was a slightly reduced risk among those who got the HPV vaccine, compared to those who were not vaccinated.1
Safe -- So Far
The scientific debate over vaccines and autoimmunity has been going on for years. Some experts contend that specific adjuvants, compounds added to vaccines to enhance immune responses, can induce autoimmune disease (notably SLE), in genetically vulnerable people.2
Studies looking at the effects of two novel adjuvants in HPV vaccines found a slight, but statistically insignificant risk of autoimmunity among women immunized in randomized clinical trials compared with controls.2
Since the first HPV vaccine, Gardasil, was licensed in 2006, the Centers for Disease Control and Prevention (CDC) has tracked adverse side effects, including autoimmune diseases such as Guillain-Barré syndrome (GBS)) and multiple sclerosis.3
GBS is a rare disorder in which immune cells damage the protective myelin sheathe around nerve cells (axons), causing muscle weakness and sometimes paralysis. GBS has been linked to viral infections (most recently to Zika virus) and, in sporadic cases, immunizations.4
Speculation is that certain proteins (peptides) in viruses and bacteria may be the same, or be similar in structure to myelin, so that antibodies the immune system produces to neutralize those threats could trigger an attack on myelin.4 As we pointed out in “The Autoimmune Connection,” such reactions could be a case of molecular mimicry and may lead to different autoimmune diseases.5
Damage in GBS is limited to peripheral axons, nerve cells outside the central nervous system in the brain and spinal cord (areas affected by MS). While most people fully recover from GBS, some do experience long-term nerve damage.4
The CDC’s Vaccine Safety Datalink has monitored adverse events after HPV immunization between August 2006 and February 2012. During that period, just over 1.4 million doses of Gardasil were administered to girls and women ages 9 to 26 years old. So far, the CDC has found no cases of GBS.3
Does HPV vaccine pose any risk?
A 2013 review of data from multiple studies by the World Health Organization’s Global Advisory Committee on Vaccine Safety concludes there has been “no increase in the risk of autoimmune diseases among girls who have received HPV vaccine compared to those who have not.” Even women who were vaccinated before they knew they were pregnant suffered no more adverse outcomes compared with those who were not vaccinated, the WHO reports.6
The largest of those studies, a register-based cohort study from Sweden and Finland, included almost 1 million girls ages 10 to 17 years, around a third of whom were vaccinated against HPV. No evidence was seen of any links between HPV vaccine and autoimmune, neurological, and venous thromboembolic events (clotting in a vein).7
An observational study in the U.S. involving almost 200,000 girls and young women who had received at least 1 dose of HPV vaccine also found no increased incidence of autoimmune diseases in the vaccinated group compared those who had not been immunized.8 The incidence of MS was not significantly higher in the vaccinated group, the study showed.
A third study cited by the WHO analyzed data from 11 clinical trials involving nearly 30,000 participants 10 years and older and also found no increased risk for autoimmune diseases with Cervarix compared with controls.9
Benefits vs. Risks
This is good news, since women with autoimmune disease are especially vulnerable to vaccine-preventable infections, says Lisen Arnheim Dahlström, PhD, of the Karolinska Institute in Stockholm, senior author of the HPV vaccine study published in July.1
Patients with rheumatoid arthritis, lupus, and other autoimmune diseases have at least 2-fold greater risk of infections compared to healthy individuals, Dahlström and her co-authors note. This may not only be due to autoimmunity but also to the immunosuppressive therapies needed to control disease activity.10
For example, there have been suggestions that therapies such as methotrexate and rituximab (Rituxan) may reduce or impair responses to common vaccines, including flu shots, while tumor necrosis factor alpha (TNF-α) drugs do not.11
Some research has found “mildly impaired” immune responses to vaccines among patients on long-term immunosuppressive therapy, but a 2008 German study concluded that “postvaccination antibody titers are usually sufficient to provide protection for the majority of immunized individuals.”8 The authors of that study contend that “the accumulated data on the safety and effectiveness of vaccines warrant immunization with the majority of vaccines for patients with chronic autoimmune or rheumatic diseases.”
The CDC stresses that studies of the HPV vaccines “have followed vaccinated individuals for ten years, and show that there is no evidence of weakened protection over time.”12
The CDC recommends HPV vaccination for 11 and 12 year-old girls, and girls and women ages 13 through 26, ideally before they become sexually active,13 a guideline supported by the American College of Rheumatology.
The WHO says it “remains reassured by the safety profile of the vaccine,” but stresses the importance of continued monitoring.
As for the risk-benefit profile, the WHO concludes “allegations of harm due to vaccination based on incomplete information may lead to unnecessary harm when effective vaccines are not used.”
Issues to discuss with your doctor for sure.
1 Grönlund O, Herweijer E, K. Sundström K, and Arnheim-Dahlström L. Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study. Journ Int Med. Early View Online, July 31, 2016. DOI: 10.1111/joim.12535
2 Orbach H, Agmon-Levin N, Zandman-Goddard G. Vaccines and autoimmune diseases of the adult. J Intern Med. 2012 Feb;271(2):193-203. doi: 10.1111/j.1365-2796.2011.02467.x.
3 Centers for Disease Control and Prevention (CDC): Frequently Asked Questions about HPV Vaccine Safety. http://www.cdc.gov/vaccinesafety/vaccines/hpv/hpv-safety-faqs.html#A6b
4 National Institute for Neurological Diseases and Stroke (NINDS). Guillain Barré Syndrome Fact Sheet. http://www.ninds.nih.gov/disorders/gbs/detail_gbs.htm
5 Baron-Faust R, Buyon JP. “The Autoimmune Connection, 2nd Edition,” 2016, McGraw-Hill, NY. Pp. 8, 26, 290, 395.
6 World Health Organization (WHO), Global Advisory Committee on Vaccine Safety, 11–12 December 2013, Geneva, Switzerland. WHO Weekly Epidemiological Record.> 2014;7(89):53–60. Online 14 February 2014. http://www.who.int/wer, retrieved August 1, 2016.
7 Arnheim-Dahlström L, 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 9; 347.doi: http://dx.doi.org/10.1136/bmj.f5906
8 Chao C et al. Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med. 2012 Feb;271(2):193-203. doi: 10.1111/j.1365-2796.2011.02467.x.
9 Descamps D, et al. Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Hum Vaccin. 2009;5(5):332-40. Epub 2009 May 20.
10 Glück T and Müller-Ladner U. Vaccination in Patients with Chronic Rheumatic or Autoimmune Diseases. Clin Infect Dis. 2008; 46(9): 1459-1465.doi: 10.1086/587063
11 Hua C, Barnetche T, Combe B, Morel J. Effect of Methotrexate, Anti–Tumor Necrosis Factor α, and Rituximab on the Immune Response to Influenza and Pneumococcal Vaccines in Patients With Rheumatoid Arthritis: A Systematic Review and MetaAnalysis. Arthritis Care & Research. 2014;66:1016–1026. doi: 10.1002/acr.22246.
12 CDC, HPV Vaccine Information for Young Women. http://www.cdc.gov/std/hpv/stdfact-hpv-vaccine-young-women.htm.
13 Kim DK, Bridges CB, Harriman KH, et al., CDC Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older — United States, 2016. Morbidity and Mortality Weekly Report (MMWR). February 5, 2016 / 65(4);88–90.
14 Singh JA, Saag KG, Bridges SL, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2015. doi:10.1002/acr.22783.ch02.