The HPV Vaccine and Autoimmunity: Reviewing the Research

Paul A. Offit, MD


September 15, 2016

Editorial Collaboration

Medscape &

What Is Needed to Prove That HPV Vaccines Induce Autoimmunity?

Good medical practice is based on biologic plausibility and scientific evidence. The recent case series and reports (see Chronic Symptoms After HPV Vaccine: Part of Wider Syndrome?) that led to this review do not meet the criteria necessary to prove any relationship between HPV vaccine and autoimmune issues. To make such a connection, the following criteria must be met.

First, investigators must show that one or more of the L1 proteins that comprise HPV4 mimic self-antigens and that self-antigen–specific T or B cells are present in the circulation.

Second, self-antigens must be present in quantities necessary to evoke autoimmune responses. The HPV4 vaccine contains 20 µg, 40 µg, 40 µg, and 20 µg of the L1 proteins from HPV serotypes 6, 11, 16, and 18, respectively. That is not likely to be enough protein to induce autoimmunity.

Another way to look at this would be to note the differences between Lyme disease and Lyme vaccine. Lyme disease causes autoimmune arthritis, but Lyme vaccine doesn't, even though the Lyme vaccine contains a protein that mimics a self-antigen. Lyme bacteria replicate in joints, generating large amounts of self-proteins. The Lyme vaccine (LYMErix™), on the other hand, contained only 30 µg of the outer surface A protein, which—although it mimicked the LFA-1 self-antigen—wasn't enough to induce autoimmunity.[5,6]

Third, costimulatory signals, cytokines, and other activation signals produced by antigen-presenting cells like dendritic cells are necessary to drive autoimmune responses. Although live viruses and bacteria can drive these responses at levels necessary to induce autoimmunity, inactivated viruses or purified proteins don't drive these response nearly as strongly—at least not without a powerful adjuvant, like squalene or oil-in-water emulsions.

Fourth, peripheral tolerance mechanisms, which the body uses to prevent autoimmune responses from the moment of birth, must fail. Again, no evidence for breaking tolerance has been shown for HPV vaccines.

In summary, well-controlled epidemiologic studies have failed to show that autoimmune diseases are associated with HPV vaccination. Given what is known about the immunologic requirements for autoimmunity, the results of these studies were predictable.


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