VICP Registry Case Source Bundle
Canonical URL: https://vicp-registry.org/case/USCOURTS-cofc-1_15-vv-00734
Package ID: USCOURTS-cofc-1_15-vv-00734
Petitioner: Amy N. Heddens
Filed: 2015-10-05
Decided: 2019-04-30
Vaccine: HPV
Vaccination date: 2012-12-03
Condition: multiple sclerosis
Outcome: denied
Award amount USD: 

AI-assisted case summary:
Amy N. Heddens received her third dose of the HPV vaccine on December 3, 2012. She alleged that this vaccination caused or significantly aggravated multiple sclerosis (MS). Prior to vaccination, on June 30, 2010, she had experienced symptoms including frequent urination, loss of balance, and blurry vision, which one expert opined could have been an initial manifestation of MS. However, the physician's assistant who saw her at that time did not attribute significance to these symptoms. After vaccination, on January 18, 2013, Ms. Heddens experienced double vision and dizziness, leading to an MRI that revealed multiple enhancing lesions in her brain. A neurologist diagnosed her with MS. Both parties' experts agreed on the MS diagnosis, but differed on the timing of the initial manifestation. The court found that Ms. Heddens likely had brain lesions before the vaccination, leading the case to be analyzed as a significant aggravation claim. To succeed, she had to prove that the HPV vaccine could cause an exacerbation of MS. The court found she failed to meet this burden, relying on epidemiological studies that did not support a link between the HPV vaccine and MS, and finding that the proposed theory of molecular mimicry, supported by expert testimony and two articles, lacked sufficient empirical evidence to establish a probability of causation. The Special Master denied compensation, and this decision was affirmed on review by the Court of Federal Claims.

Theory of causation field:
Off-Table

Public staged source text:

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DOCUMENT 1: USCOURTS-cofc-1_15-vv-00734-1
Date issued/filed: 2018-11-01
Pages: 6
Docket text: PUBLIC DECISION (Originally filed: 10/5/2018) regarding 94 DECISION of Special Master. Signed by Special Master Christian J. Moran. (abs) Service on parties made.
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Case 1:15-vv-00734-PEC Document 101 Filed 11/01/18 Page 1 of 6
In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
* * * * * * * * * * * * * * * * * * * * * * * * *
AMY N. HEDDENS, *
* No. 15-734V
Petitioner, * Special Master Christian J. Moran
*
v. *
* Filed: October 5, 2018
SECRETARY OF HEALTH *
AND HUMAN SERVICES, * Entitlement, HPV vaccine,
* multiple sclerosis, bench ruling
Respondent. *
* * * * * * * * * * * * * * * * * * * * * * * * *
Ronald C. Homer & Meredith Daniels, Conway & Homer, P.C., Boston, MA, for petitioner;
Christine Becer, United States Dep’t of Justice, Washington, DC, for respondent.
PUBLISHED DECISION DENYING COMPENSATION1
A hearing was held on October 1, 2018. After the parties submitted all their evidence,
the undersigned issued a bench decision, finding that Ms. Heddens had failed to establish that
she was entitled to compensation. See Doe/17 v. Secʼy of Health & Human Servs., 84 Fed. Cl.
691, 704 n. 18 (2008) (noting “[e]ven a special master’s ruling on entitlement may be delivered
from the bench, with no written opinion”).
The undersigned is issuing this document for two reasons. First, if only a bench decision
was issued, the public would not have access to the transcript containing the bench decision and,
thereby, the reasoning underlying the decision. To allow public access to the reasoning
underlying the decision, this document will become available to the public pursuant to 42 U.S.C.
§ 300aa-12(d)(4).
Second, this document provides an abbreviated recitation for the basis of decision. See
Hebern v. United States, 54 Fed. Cl. 548 (2002) (example of a judge from the United States
Court of Federal Claims formalizing a bench ruling denying a motion for review). As explained
in the bench ruling, the undersigned considered all the evidence, including the medical records,
1 The E-Government Act, 44 U.S.C. § 3501 note (2012) (Federal Management and
Promotion of Electronic Government Services), requires that the Court post this decision on its
website. This posting means that the decision will be available to anyone with the internet.
Pursuant to Vaccine Rule 18(b), the parties have 14 days to file a motion proposing redaction of
medical information or other information described in 42 U.S.C. § 300aa-12(d)(4). Any
redactions ordered by the special master will appear in the document posted on the website.

Case 1:15-vv-00734-PEC Document 101 Filed 11/01/18 Page 2 of 6
expert reports, medical articles, and oral testimony. The undersigned’s consideration of this
evidence began when the evidence was received. See Vaccine Rule 5.
The evidence shows that relatively few events in Ms. Heddens’s medical record hold
significance for determining whether she is entitled to compensation. On June 30, 2010, she
went to a clinic for a “well woman exam,” during which she reported frequent urination, loss of
balance, and blurry vision when she moved her head. She also reported diarrhea and nausea.
Exhibit 5 at 8. The expert whom the Secretary retained, Dr. Sriram, opined that this episode was
an initial manifestation of multiple sclerosis (“MS”). Exhibit M at 2. In contrast, the expert
whom Ms. Heddens retained, Dr. Napoli, disagreed. Exhibit 29 at 2. The person who conducted
the June 30, 2010 examination, a physician’s assistant named Cindy Shuman, seemed not to
attribute any significance to these problems as Ms. Shuman did not suggest any follow up. See
exhibit 5 at 10.
The next significant event in Ms. Heddens’s medical history was her receipt of the third
dose of the HPV vaccine on December 3, 2012. Between June 30, 2010 and December 2, 2012,
Ms. Heddens did not report having any problems that the experts considered related to multiple
sclerosis. Ms. Heddens alleges that the December 3, 2012 HPV vaccination harmed her.2
On January 18, 2013, Ms. Heddens experienced double vision and dizziness for which
she sought treatment at an urgent care facility. She was referred to an emergency room. Exhibit
9 at 3. The emergency room doctor, in turn, referred her to an ophthalmologist. Exhibit 3 at 5-6.
The ophthalmologist ordered an MRI. Exhibit 10 at 2.
The MRI was conducted on January 29, 2013. It showed multiple enhancing lesions.
Exhibit 3 at 64-65.
When a neurologist, Dr. Ramirez, reviewed the results of the MRI, he diagnosed Ms.
Heddens as suffering from MS. Exhibit 4 at 1-4.3 Both Dr. Napoli and Dr. Sriram agree with
the diagnosis of multiple sclerosis, although they, as mentioned earlier, differ as to whether Ms.
Heddens’s first clinical manifestation of MS was in June 2010 or January 2013. After Dr.
Ramirez’s diagnosis in 2013, Ms. Heddens has received medical care periodically. None of her
treating doctors suggested that the HPV vaccination harmed Ms. Heddens. See Pet’r’s Br. at 46-
48; Resp’t’s Br. at 13. Otherwise, the details of the course of Ms. Heddens’s MS are not relevant
to determining whether the December 3, 2012 HPV vaccination harmed Ms. Heddens.
The analysis begins with a preliminary, but ultimately insignificant, issue — whether Ms.
Heddens’s case should be analyzed either as a claim that the HPV vaccine caused her to suffer an
initial onset of MS or as a claim that the HPV vaccine caused her to suffer an aggravation of pre-
existing MS. The undisputed testimony from the experts indicate that Ms. Heddens, most likely,
2 Initially, Ms. Heddens alleged that the HPV vaccination caused her to suffer multiple
sclerosis. But, as part of her pre-hearing brief, Ms. Heddens presented the alternative claim that
the HPV vaccination significantly aggravated pre-existing multiple sclerosis. Pet’r’s Br. at 2, 25.
3 During this initial consultation, Dr. Ramirez recorded: “She has not been sick or
received immunization recently.” Exhibit 4 at 1.
2

Case 1:15-vv-00734-PEC Document 101 Filed 11/01/18 Page 3 of 6
had lesions in her brain before the HPV vaccination on December 3, 2012. These lesions
appeared on her January 29, 2013 MRI. After Dr. Sriram reviewed the images from this MRI, he
wrote that Ms. Heddens had 10 T2 lesions and 9 active lesions. Exhibit U at 1. At the hearing,
Dr. Napoli agreed with Dr. Sriram’s observations. Further, Dr. Sriram reasoned that number,
size, and location of the lesions suggested that at least some of the lesions had to exist before the
December 3, 2012 vaccination. Exhibit U at 2-3. Dr. Napoli agreed with this conclusion. Dr.
Napoli testified that if Ms. Heddens had undergone an MRI on December 2, 2012, the day before
the vaccination, this hypothetical MRI would have probably shown lesions. Based upon the
agreement between the experts, the undersigned finds that Ms. Heddens most likely had lesions
in her brain before receiving the December 3, 2012 HPV vaccination. This finding is sufficient
to serve as a predicate for analyzing Ms. Heddens’s case as a claim for significant aggravation.4
As a significant aggravation case, Ms. Heddens must establish the elements set forth in
Loving v. Sec’y of Health & Human Servs., 86 Fed. Cl. 135, 144 (2009). Importantly, the last
three elements of the Loving test correspond to the three elements of an initial causation claim
set forth in Althen v. Sec’y of Health & Human Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005).
This decision turns on the outcome of the fourth Loving factor, which is the first Althen factor,
whether the HPV vaccination can cause an exacerbation of MS.
Ms. Heddens has failed to meet her burden of proof on this element. Beyond the opinion
from Dr. Napoli, the evidence falls into two categories: epidemiological and experimental.
The Secretary introduced epidemiological studies to undermine Ms. Heddens’s attempt to
establish that the HPV vaccine can aggravate (or cause) MS. See Bazan v. Sec’y of Health &
Human Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008) (“The government, like any defendant, is
permitted to offer evidence to demonstrate the inadequacy of the petitioner’s evidence on a
requisite element of the petitioner's case-in-chief”). Some epidemiological studies investigated
the precise question in the case at bar: whether the HPV vaccine affects MS. One article was a
meta-study of 11 underlying studies. Exhibit S.5 Another article was a study of nearly four
million women from Denmark and Sweden, countries where MS is most prevalent. Exhibit E.6
A third article, which carried the least weight, analyzed VAERS data. Exhibit F.7 Collectively,
4 Categorizing Ms. Heddens’s case as one involving significant aggravation does not
depend on the June 30, 2010 episode. As discussed during the oral bench ruling, whether the
June 30, 2010 episode represented an unrecognized manifestation of MS, as Dr. Sriram opined,
or was entirely unrelated to MS, as Dr. Napoli opined, is a closer question. But, resolution of
this close question does not affect the outcome of Ms. Heddens’s case.
5 Julie Mouchet et al., Human papillomavirus vaccine and demyelinating diseases — A
systemic review and meta-analysis, 132 Pharmacological Research 108 (2018).
6 Nikolai Madrid Scheller et al., Quadrivalent HPV Vaccination and Risk of Multiple
Sclerosis and Other Demyelinating Diseases of the Central Nervous System, 313 J. Amer. Med.
Ass’n 54 (2015).
7 Paolo Pellegrino, No evidence of a link between multiple sclerosis and the vaccine
against the human papillomavirus, 28 Eur. J. Epidemiol. 705 (2013).
3

Case 1:15-vv-00734-PEC Document 101 Filed 11/01/18 Page 4 of 6
these studies did not support Ms. Heddens’s argument that the HPV vaccine can aggravate (or
cause) MS.
Another set of epidemiological studies examined whether vaccines other than the HPV
vaccine caused or worsened MS. Exhibits C8 and I.9 They also have not detected a statistically
significant increase in multiple sclerosis after various vaccines. Because these studies are not
about the HPV vaccine, they carry less evidentiary value than the epidemiology directly on point.
But, to the extent these additional studies contribute to the analysis, they tend to show that
vaccinations do not contribute to MS.
However, epidemiology does not conclusively establish that the HPV vaccine cannot
cause MS. A petitioner can argue that if a 12th study were conducted or if a study involved five
million women, then the results might detect something that has evaded detection so far. Thus,
the finding that Ms. Heddens failed to meet her burden of proof regarding Loving prong 4 /
Althen prong 1 does not rest exclusively on the epidemiology.
Ms. Heddens relies upon Dr. Napoli’s opinion that molecular mimicry is a reliable
explanation to connect the HPV vaccination to a worsening of MS. In the pre-trial conference,
the Secretary acknowledged that molecular mimicry is a valid theory to explain why the flu
vaccine can cause Guillain-Barré syndrome.
Nevertheless, a simple invocation of the term “molecular mimicry” does not carry a
petitioner’s burden of proof. As explained by the Court of Federal Claims, “Without any
empirical evidence that the theory actually applies to the influenza vaccine and [the disease in
question], the first prong of Althen would be rendered meaningless.” Caves v. Sec’y of Health
& Human Servs., 100 Fed. Cl. 119, 135 (2011), aff’d without opinion, 463 F. App’x 932 (Fed.
Cir. 2012).
Ms. Heddens has failed to present “empirical evidence” to support Dr. Napoli’s opinion
that the HPV vaccine can aggravate (or cause) MS. At the hearing, Dr. Napoli identified two
articles as the primary support for his opinion: an article by Wucherpfennig and Strominger and
an article by Kanduc.10 But, neither article is supportive.
Wucherpfennig and Strominger.11 These researchers explored whether various foreign
antigens (viruses and bacteria) could inspire the production of T cells that would react with
8 Frank DeStefano et al., Vaccinations and Risk of Central Nervous System
Demyelinating Diseases in Adults, 60 Arch. Neurol. 504 (2003).
9 Christian Confavreux et al., Vaccinations and the Risk of Relapse in Multiple Sclerosis,
344 N. Eng. J. Medicine 319 (2001).
10 Based, in part, on the parties’ pre-hearing briefs, the undersigned had identified those
articles as the main articles on which Ms. Heddens and Dr. Napoli were relying.
11 Kai W. Wucherpfennig and Jack L. Strominger, Molecular mimicry in T cell-mediated
autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein,
80(5) Cell 695 (1995).
4

Case 1:15-vv-00734-PEC Document 101 Filed 11/01/18 Page 5 of 6
myelin basic protein. As a first step, Wucherpfennig and Strominger consulted a database,
looking to see whether the amino acid sequence resembled (or mimicked) an epitope of myelin
basic protein. Exhibit 21, tab C at 696-97. This database query identified more than 600
antigens that had some homology. Of this group, the researchers selected certain proteins for
further testing. Of this group, seven came from types of the human papillomavirus. As a second
step, Wucherpfennig and Strominger then tested whether these homologous antigens caused an
expansion in the number of T cells that were known to react with myelin basic protein. This test
showed that some, but not all, of the homologous antigens produced a strong response. Id. at
698-99, table 1. For example, the herpes simplex virus produced relatively large numbers of T
cells. However, and importantly for this case, the seven types of the human papillomavirus did
not generate a strong response. In addition, a different table, table 2, showed some reactivity to a
part of the human papillomavirus not found in the HPV vaccine.
Dr. Sriram presented this critique in a report. Exhibit O at 2. When Dr. Napoli was
asked to comment during the hearing, he stated that this article shows that there is potentially
cross-reactivity.
Kanduc.12 Unlike the Wucherpfennig experiment, which tested the human
papillomavirus, Kanduc tested a portion of the HPV vaccine. Kanduc identified more than 80
strings composed of seven amino acids, known as heptapeptides, from HPV16 that matched
sequences of amino acids in the human proteome. Based upon the function of the protein,
Kanduc proposed that cross-reactivity could cause various problems. Exhibit 23, tab A at 66.
But, none of those problems resemble the problems that appear in MS.13
When Dr. Napoli was asked about the limitations of Kanduc, he also responded that
Kanduc shows the HPV vaccination could maybe serve as a trigger for an autoimmune reaction.
This is true. Cross-reactivity is possible in theory. But, Ms. Heddens has provided no reliable
basis for elevating this potentiality to a probability.
Requiring Ms. Heddens to present some support for the theory she proposes is consistent
with W.C. v. Secʼy of Health & Human Servs., 704 F.3d 1352, 1360 (Fed. Cir. 2013), in which
the Federal Circuit stated that although molecular mimicry may be well-regarded in some
contexts, the special master “correctly required additional evidence showing that molecular
mimicry can cause the influenza vaccine to significantly aggravated multiple sclerosis.” The
Federal Circuit further examined the special master’s finding that the Wucherpfennig article
showed some peptides were cross-reactive but others were not, and concluded that the special
master’s weighing of this evidence was not arbitrary or capricious. Id. at 1360-61. The support
a petitioner provides does not have to reach a level of reliability that the theory is scientifically
certain. See LaLonde v. Secʼy of Health & Human Servs., 746 F.3d 1334, 1339 (Fed. Cir. 2014)
(“simply identifying a ‘plausible’ theory of causation is insufficient for a petitioner to meet her
12 Darja Kanduc, Quantifying the possible cross-reactivity risk of an HPV16 vaccine, 8 J
Experimental Therapeutics and Oncology 65 (2009).
13 Ms. Heddens elicited testimony that one homologous protein, GALC, contributes to the
production of myelin. However, according to Kanduc, the consequences of deficiencies in
GALC appear before an individual is six months old. See exhibit 23, tab A at 72-73.
5

Case 1:15-vv-00734-PEC Document 101 Filed 11/01/18 Page 6 of 6
burden of proof”). But, even at the more-likely-than-not level of proof, Ms. Heddens has not
overcome this hurdle.
A persuasive showing that the HPV vaccine can worsen (or cause) MS is, as explained
above, part of Ms. Heddens’s case under either the Loving or Althen framework. She has failed
to meet the required showing. Thus, regardless of whether her claim is one for significant
aggravation (based upon the uncontroverted assertion that she most likely had lesions in her
brain before the vaccination) or whether her claim is a new onset claim, she is not entitled to
compensation.
The undersigned directs the Clerk’s Office to enter judgment based upon the decision in
this case if a motion for review is not filed. When the time for filing a motion for review (see
Vaccine Rule 23) begins to run is for an appellate tribunal to decide.
IT IS SO ORDERED.
s/Christian J. Moran
Christian J. Moran
Special Master
6

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DOCUMENT 2: USCOURTS-cofc-1_15-vv-00734-2
Date issued/filed: 2019-04-30
Pages: 11
Docket text: JUDGE VACCINE REPORTED OPINION: Pursuant to Rule 18(b) of the Vaccine Rules of this court, this opinion was initially filed under seal on 3/12/2019, see 106 Opinion on Motion for Review. Pursuant to paragraph 4 of the ordering language, the parties were to propose redactions of the information contained therein on or before 3/26/2019. No proposed redactions were submitted to the court. Signed by Judge Patricia E. Campbell-Smith. (TQ) Service on parties made.
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Case 1:15-vv-00734-PEC Document 108 Filed 04/30/19 Page 1 of 11
In the United States Court of Federal Claims
No. 15-734V
(E-Filed: April 30, 2019)1
____________________________________
)
AMY N. HEDDENS, )
Vaccine (human papillomavirus);
)
National Childhood Vaccine
Petitioner, )
Injury Act of 1986, 42 U.S.C. §§
)
300aa-1 to -34 (2012); Deferential
v. )
Review of the Special Master’s
)
Fact Finding and Weighing of the
SECRETARY OF HEALTH AND )
Evidence.
HUMAN SERVICES, )
)
Respondent. )
____________________________________)
Ronald C. Homer, Boston, MA, for petitioner.
Christine M. Becer, Trial Attorney, with whom were Joseph H. Hunt, Assistant Attorney
General, C. Salvatore D’Alessio, Acting Director, Catharine E. Reeves, Deputy Director,
Gabrielle M. Fielding, Assistant Director, Torts Branch, Civil Division, United States
Department of Justice, Washington, DC, for respondent.
OPINION AND ORDER
CAMPBELL-SMITH, Judge.
On October 5, 2018, the special master issued his decision denying compensation
in this vaccine case. See ECF No. 94. On October 31, 2018, petitioner filed: (1) a
motion for review of the special master’s decision, ECF No. 97; and (2) the memorandum
in support of the motion for review, ECF No. 99. Respondent filed its response brief on
1 Pursuant to Rule 18(b) of the Vaccine Rules of the United States Court of Federal
Claims (Appendix B to the Rules of the United States Court of Federal Claims), this
opinion was initially filed under seal on March 12, 2019. Pursuant to ¶ 4 of the ordering
language, the parties were to propose redactions of the information contained therein on
or before March 26, 2019. No proposed redactions were submitted to the court.

Case 1:15-vv-00734-PEC Document 108 Filed 04/30/19 Page 2 of 11
November 30, 2018. See ECF No. 102. Petitioner’s motion is fully briefed and ripe for
decision.
The special master denied petitioner compensation under the National Childhood
Vaccine Injury Act of 1986, 42 U.S.C. §§ 300aa-1 to -34 (2012) (the Vaccine Act). As
explained below, the special master’s entitlement decision survives this court’s review.
Accordingly, the court must DENY petitioner’s motion for review.
I. Background
On June 30, 2010, petitioner visited a clinic for a “well woman exam.” There, she
reported “frequent urination, loss of balance, and blurry vision when she moved her
head,” as well as diarrhea, a late period, and nausea. ECF No. 94 at 2; see also ECF No.
96 at 19-21 (transcript of the evidentiary hearing held on October 1, 2018).
On December 3, 2012, petitioner received her third dose of the human
papillomavirus (HPV) vaccine. ECF No. 94 at 2. On January 18, 2013, petitioner
experienced “double vision and dizziness.” Id. She went to an urgent care facility for
evaluation. Id. The urgent care doctor referred petitioner to an emergency room, from
which she was referred to an ophthalmologist. Id. On January 29, 2013, petitioner
received a magnetic resonance imaging scan (MRI) that showed “multiple enhancing
lesions” throughout her brain. Id. Thereafter, a neurologist diagnosed petitioner with
multiple sclerosis (MS). Id. On July 16, 2015, petitioner requested Vaccine Act
compensation on the theory that her MS “was caused-in-fact” by the HPV vaccine. ECF
No. 1 (petition). In her memorandum in support of her motion for review, petitioner
characterizes her claim as alleging “that her HPV vaccination caused a significant
aggravation of an underlying, subclinical MS.” ECF No. 99 at 6.
On October 1, 2018, the special master held an evidentiary hearing. See ECF No.
96. During the hearing, the special master heard testimony from both petitioner’s expert,
Dr. Salvatore Napoli, and respondent’s expert, Dr. Subramaniam Sriram. See id. At the
close of the hearing, the special master issued a ruling from the bench and denied
petitioner’s request for compensation. See id. at 229-53. In issuing his ruling, the special
master explained: “[W]hat I look at first is the epidemiology, and that does not seem to
support the theory that HPV vaccine causes or affects multiple sclerosis. I realize that
[Althen v. Sec’y of Health & Human Servs., 418 F.3d 1274 (Fed. Cir. 2005),] says that
epidemiology is not required, but epidemiology remains a relevant factor.” Id. at 239.
He also stated:
I tend to give the epidemiology great weight. That’s how I tend to view the
evidence. I think [Whitecotton v. Sec’y of Health & Human Servs., 81 F.3d
1099 (Fed. Cir. 1996),] says that how much weight Special Masters give to
evidence is a discretionary function of a Special Master. So I think some
2

Case 1:15-vv-00734-PEC Document 108 Filed 04/30/19 Page 3 of 11
Special Masters may weigh epidemiology different[ly] than I do, but I tend
to give it more weight.
Id. at 242.
The bench ruling was later memorialized in a written decision issued four days
later, on October 5, 2018. See ECF No. 94. As an initial matter, the special master
explained that: “the undersigned considered all the evidence, including the medical
records, expert reports, medical articles, and oral testimony.” Id. at 1-2. The special
master reiterated his conclusion that petitioner had failed to carry her burden of
demonstrating that “the HPV vaccine can worsen (or cause) MS,” and concluded that
“regardless of whether her claim is one for significant aggravation . . . or whether her
claim is a new onset claim, she is not entitled to compensation.” Id. at 6.
The special master’s decision noted that the “undisputed testimony from the
experts indicate[s] the [petitioner], most likely, had lesions in her brain before the HPV
vaccination on December 3, 2012.” Id. at 2-3. For this reason, the special master
analyzed petitioner’s case “as a claim for significant aggravation,” and applied the factors
set forth in this court’s opinion in Loving v. Sec’y of Health & Human Servs., 86 Fed. Cl.
135, 144 (2009). The special master noted that “[t]his decision turns on the outcome of
the fourth Loving factor . . . whether the HPV vaccination can cause an exacerbation of
MS.” Id.
From there, the special master proceeded to evaluate expert testimony, along with
epidemiological and experimental evidence. The epidemiological evidence included a
variety of studies that had been submitted by respondent in an effort to undermine
petitioner’s claim—some, but not all of which, addressed the connection between the
HPV vaccine and MS. See id.; see also id. at 3-4 (describing and citing to the studies
presented by respondent). The special master assigned “less evidentiary value” to the
studies that did not specifically involve the HPV vaccine. Id. at 4. He concluded that the
studies did not tend to support petitioner’s case but also observed that “epidemiology
does not conclusively establish that the HPV vaccine cannot cause MS.” Id. As such, the
conclusion that petitioner failed to carry her burden under the fourth Loving factor “does
not rest exclusively on the epidemiology.” Id.
Petitioner’s expert posited a theory that molecular mimicry explains the
connection between the HPV vaccine and MS, and offered two articles as support. Id. at
4-5. The first article, by Kai W. Wucherpfennig and Jack L. Strominger,2 “explored
2 Kai W. Wucherpfennig & Jack L. Strominger, Molecular mimicry in T cell-
mediated autoimmunity: viral peptides activate human T cell clones specific for myelin
basic protein, 80(5) Cell 695 (1995). See ECF No. 94 at 4 n.11.
3

Case 1:15-vv-00734-PEC Document 108 Filed 04/30/19 Page 4 of 11
whether various foreign antigens (viruses and bacteria) could inspire the production of T
cells that would react with myelin basic protein.” Id. A review of relevant data revealed
that “the human papillomavirus did not generate a strong response” in this context. Id. at
5. The second article, by Darja Kanduc,3 addressed the HPV vaccine, and proposed that
cross-reactivity with certain proteins could cause complications. See id. “But, none of
those problems resemble the problems that appear in MS.” Id. The special master
acknowledged that these articles presented possible theories, but concluded that they
were not persuasive enough to carry petitioner’s burden. Id. at 5-6.
II. Legal Standards
This court has jurisdiction to review the decision of a special master in a Vaccine
Act case. 42 U.S.C. § 300aa-12(e)(2). “Under the Vaccine Act, the Court of Federal
Claims reviews the decision of the special master to determine if it is ‘arbitrary,
capricious, an abuse of discretion, or otherwise not in accordance with law[.]’” de Bazan
v. Sec’y of Health & Human Servs., 539 F.3d 1347, 1350 (Fed. Cir. 2008) (quoting 42
U.S.C. § 300aa-12(e)(2)(B) and citing Althen, 418 F.3d at 1277) (alteration in original).
This court uses three distinct standards of review in Vaccine Act cases, depending
upon which aspect of a special master’s judgment is under scrutiny.
These standards vary in application as well as degree of deference. Each
standard applies to a different aspect of the judgment. Fact findings are
reviewed . . . under the arbitrary and capricious standard; legal questions
under the “not in accordance with law” standard; and discretionary rulings
under the abuse of discretion standard.
Munn v. Sec’y of Dep’t of Health & Human Servs., 970 F.2d 863, 870 n.10 (Fed. Cir.
1992).
The third standard of review, abuse of discretion, is applicable when the special
master excludes evidence or otherwise limits the record upon which he or she relies. See
id. at 870. As this court has stated, the third standard applies to the special master’s
evidentiary rulings. Stillwell v. Sec’y of Health & Human Servs., 118 Fed. Cl. 47, 55
(2014) (citation omitted), aff’d, 607 F. App’x 997 (Fed. Cir. 2015). Determinations
subject to review for abuse of discretion must be sustained unless “manifestly erroneous.”
Piscopo v. Sec’y of Health & Human Servs., 66 Fed. Cl. 49, 53 (2005) (citations
omitted); see also Milmark Servs., Inc. v. United States, 731 F.2d 855, 860 (Fed. Cir.
1984) (holding that decisions within the trial court’s discretion are to be sustained unless
“manifestly erroneous”) (citation omitted).
3 Darja Kanduc, Quantifying the possible cross-reactivity risk of an HPV16 vaccine,
8 J. Experimental Therapeutics & Oncology 65 (2009). See ECF No. 94 at 5 n.12.
4

Case 1:15-vv-00734-PEC Document 108 Filed 04/30/19 Page 5 of 11
A petitioner may obtain compensation if she “sustained, or had significantly
aggravated, any illness, disability, injury, or condition not set forth in the Vaccine Injury
Table but which was caused by” certain vaccines, including the HPV vaccine. 42 U.S.C.
§ 300aa-11(c)(1)(C)(ii). A case for significant aggravation of an off-Table claim requires
proof, by a preponderance of the evidence of:
(1) the person’s condition prior to administration of the vaccine, (2) the
person’s current condition (or the condition following the vaccination if that
is also pertinent), (3) whether the person’s current condition constitutes a
“significant aggravation” of the person’s condition prior to vaccination, (4)
a medical theory causally connecting such a significantly worsened condition
to the vaccination, (5) a logical sequence of cause and effect showing that
the vaccination was the reason for the significant aggravation, and (6) a
showing of a proximate temporal relationship between the vaccination and
the significant aggravation.
Loving, 86 Fed. Cl. at 144; see also W.C. v. Sec’y of Health & Human Servs., 704 F.3d
1352, 1360 (Fed. Cir. 2013) (referring to the Loving test as “the correct law”).
III. Analysis
In her memorandum in support of her motion for review, petitioner raises four
objections to the special master’s decision. First, petitioner objects to the special
master’s reliance on epidemiological studies that do not address the HPV vaccine. See
ECF No. 99 at 15-16. Second, petitioner objects to the special master’s reliance on an
article by Nikolai Madrid Scheller.4 Id. at 17-19. Third, petitioner objects more
generally to the special master’s reliance on epidemiology. Id. at 19-25. And fourth,
petitioner objects to the special master’s determination that she failed to meet her burden
under Loving factor four by presenting a theory of molecular mimicry. Id. at 25-31. The
court will address each argument in turn.
A. The Special Master Did Not Abuse His Discretion in Considering Studies
that Did Not Involve the HPV Vaccine
Regarding her first objection, petitioner argues that the special master “gave
substantial weight to epidemiologic studies that did not examine the HPV vaccination and
MS.” ECF No. 99 at 15. Petitioner asserts that the special master’s “reliance on these
studies in any capacity is not in accordance with the law.” Id. at 16. In particular,
petitioner argues that such consideration violates the standard observed in Moberly v.
4 Nikolai Madrid Scheller et al., Quadrivalent HPV Vaccination and Risk of
Multiple Sclerosis and Other Demyelinating Diseases of the Central Nervous System,
313 J. Amer. Med. Ass’n 54 (2015). See ECF No. 94 at 3 n.6.
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Secretary of Health & Human Services, 592 F.3d 1315 (Fed. Cir. 2010), that “[a]s a
general matter, epidemiological studies are designed to reveal statistical trends only for a
carefully constructed test group. Such studies provide no evidence pertinent to persons
not within the parameters of the test group.” Id. (quoting Moberly, 592 F.3d at 1324).
Petitioner is correct that some of the studies cited by the special master do not
involve the HPV vaccine.5 The special master, however, acknowledged as much, and
weighted the evidence accordingly. See ECF No. 94 at 4. He stated: “Because these
studies are not about the HPV vaccine, they carry less evidentiary value than the
epidemiology directly on point. But, to the extent these additional studies contribute to
the analysis, they tend to show that vaccinations do not contribute to MS.” Id. In vaccine
cases, a special master “must consider all relevant and reliable evidence governed by
principles of fundamental fairness to both parties.” Rule 8(b)(1) of the Vaccine Rules of
the United States Court of Federal Claims, Appendix B to the Rules of the United States
Court of Federal Claims. And as the United States Court of Appeals for the Federal
Circuit has held, “epidemiological studies are probative medical evidence relevant to
causation.” Grant v. Sec’y of Dep’t of Health & Human Servs., 956 F.2d 1144, 1149
(Fed. Cir. 1992). See also Andreu ex rel. Andreu v. Sec’y of Dep’t of Health & Human
Servs., 569 F.3d 1367, 1379 (Fed. Cir. 2009) (stating that although a “claimant need not
produce medical literature of epidemiological evidence to establish causation under the
Vaccine Act, where such evidence is submitted, the special master can consider it in
reaching an informed judgment as to whether a particular vaccination likely caused a
particular injury”).
Neither party has cited, nor is the court aware of, any precedent requiring a special
master to wholly reject consideration of epidemiological evidence if such evidence is not
directly applicable to the facts of the case at bar. See, e.g., D’Tiole v. Sec’y of Health &
Human Servs., 726 F. App’x 809, 811 (Fed. Cir. 2018) (“Nothing in Althen or
[Capizzano v. Sec’y of Health & Human Servs., 440 F.3d 1317 (Fed. Cir. 2006)] requires
the Special Master to ignore probative epidemiological evidence that undermines
petitioner’s theory.”); Grant, 956 F.2d at 1148-49 (considering negative epidemiological
evidence). Moreover, the special master explicitly stated that the “epidemiology does
not conclusively establish that the HPV vaccine cannot cause MS.” ECF No. 94 at 4.
For this reason, his conclusion “does not rest exclusively on the epidemiology.” Id.
It is clear to the court that the special master considered the epidemiological
evidence presented by respondent, but did not treat that evidence as weighing heavily
5 The articles included in this section of the special master’s decision are: Frank
DeStefano et al., Vaccinations and Risk of Central Nervous System Demyelinating
Diseases in Adults, 60 Arch. Neurol. 504 (2003) and Christian Confavreux et al.,
Vaccinations and the Risk of Relapse in Multiple Sclerosis, 344 N. Eng. J. Medicine 319
(2001). See ECF No. 94 at 4 nn.8-9.
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against petitioner, much less determinative of the issue at bar. The court, therefore,
cannot agree that the special master abused his discretion by citing to the studies that
respondent submitted in reaching his decision.
B. The Special Master Did Not Abuse His Discretion by Failing to Address
Every Flaw in the Scheller Study
In her second objection, petitioner alleges that the special master failed to account
for various flaws in the Scheller study—another study offered into evidence by
respondent. ECF No. 99 at 19. “[P]etitioner agrees that the overall conclusion of the
Scheller study did not find a statistically significant increased risk of demyelinating
disease following the HPV vaccination,” id. at 17, but claims that the special master’s
“heavy reliance on the Scheller study, without acknowledgment of the flaws of the study,
concessions of respondent’s expert, and importantly, a showing of higher crude incidence
rate of MS in the vaccinated population aged 30-44, constitutes an abuse of discretion,”
id. at 19.
The special master cited the Scheller study as one of several epidemiological
studies in his written decision, before stating that “[c]ollectively, these studies did not
support [petitioner’s] argument that the HPV vaccine can aggravate (or cause) MS.” ECF
No. 94 at 3-4. Put another way, the special master concluded that the studies presented
by respondent did not support petitioner’s case. Nor does petitioner claim that had the
special master accounted for the flaws she alleges, the study would have assisted her in
carrying the burden of proof. And in any event, as the court noted with respect to
petitioner’s first objection, the special master explicitly stated that his conclusion “does
not rest exclusively on the epidemiology.” ECF No. 94 at 4.
Moreover, as instructed by the Federal Circuit, the court “generally presume[s]
that a special master considered the relevant record evidence even though he does not
explicitly reference such evidence in his decision.” Moriarty v. Sec’y of Health &
Human Servs., 844 F.3d 1322, 1328 (Fed. Cir. 2016). See also ECF No. 96 at 232 (the
special master stating “I think I have considered all of the evidence even though I may
not mention everything”). Petitioner’s own brief outlines the testimony elicited at the
evidentiary hearing from respondent’s expert addressing a number of the alleged
weaknesses in the Scheller study. See ECF No. 99 at 17-18. As such, the court will not
presume—as petitioner asserts—that the special master failed to consider various ways in
which the Scheller study may not directly apply to petitioner’s case.
For these reasons, it was not an abuse of discretion to cite the Scheller study
without also reciting all of petitioner’s objections to that study.
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C. The Special Master Did Not Abuse His Discretion in Considering
Epidemiology and Did Not Elevate Petitioner’s Burden of Proof
Petitioner’s third objection is that the special master erred in placing “great
weight” on epidemiology in his analysis, which allegedly had the effect of elevating
petitioner’s burden. ECF No. 99 at 24 (“To value epidemiology with such fervor, and
specifically state that it is given ‘great weight’ compared to other special masters is an
abuse of discretion, and not in accordance with law.”); id at 25 (arguing that “[t]he
weight with which the Special Master relied on epidemiology is an abuse of discretion,
which heightened petitioner’s burden”).
As the court has noted several times in the course of this short opinion, the special
master explicitly stated that the “epidemiology does not conclusively establish that the
HPV vaccine cannot cause MS,” and for this reason, his conclusion “does not rest
exclusively on the epidemiology.” ECF No. 94 at 4. The special master also
acknowledged from the bench that “there’s a limit to epidemiology,” that petitioner “is
not required to submit epidemiology to prove [her] case,” and that “epidemiology cannot
prove a negative no matter how large the study.” ECF No. 96 at 242-43. And because
the special master “consider[ed] the record as a whole,” the decision did not rest
entirely—or even primarily—on his view of the epidemiology. Id. at 231.
There is simply no indication in the special master’s decision that he regarded the
epidemiological evidence with what petitioner calls “fervor,” even if he expressed a
preference, that may or may not differ from other special masters, for considering such
evidence.
And as to petitioner’s claim that the weight given to epidemiological studies had
the effect of heightening petitioner’s burden, the court does not agree. Petitioner’s brief
does not explain this contention in any detail. The court understands it, however, to be an
argument that because the special master allegedly over-valued epidemiological evidence
submitted by respondent, that consideration became an additional obstacle to petitioner
proving her case. The special master, however, did not inappropriately value the
epidemiological evidence submitted by respondent. And he did not conclude that the
evidence disproved—or even weighed against—petitioner’s theory. He simply stated
that “[c]ollectively, these studies did not support [petitioner’s] argument that the HPV
vaccine can aggravate (or cause) MS.” ECF No. 94 at 4. The court fails to see how this
impacts, much less heightens, petitioner’s burden.
D. The Special Master Did Not Abuse His Discretion in Analyzing Petitioner’s
Proof of Causation
Petitioner’s fourth objection challenges the special master’s ruling on Loving
factor four. Petitioner’s position is that molecular mimicry between the HPV vaccine and
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myelin basic protein “activates T cells that are cross-reactive with self-antigens,” thereby
triggering an immune reaction. ECF No. 99 at 26. The special master determined that
the molecular mimicry theory was insufficient to carry petitioner’s burden, because she
did not present persuasive empirical evidence to support the notion that the HPV vaccine
can aggravate MS. See ECF No. 94 at 4.
To satisfy Loving factor four, a petitioner “must provide a reputable medical or
scientific explanation that pertains specifically to the petitioner’s case, although the
explanation need only be ‘legally probable, not medically or scientifically certain.’”
Moberly, 592 F.3d at 1322 (quoting Knudsen v. Sec’y of Health & Human Servs., 35
F.3d 543, 548-49 (Fed. Cir. 1994)). For a theory to be “probable,” it must be more than
merely “plausible” or “possible.” Id.; see also LaLonde v. Sec’y of Health & Human
Servs., 746 F.3d 1334, 1339 (Fed. Cir. 2014) (“simply identifying a ‘plausible’ theory of
causation is insufficient for a petitioner to meet her burden of proof”) (citing Moberly,
592 F.3d at 1322).
Petitioner challenges the way the special master analyzed petitioner’s molecular
mimicry theory. The special master discounted the Wucherpfennig article because, in his
view, that study did not find that HPV produced a “strong response” in terms of T-cell
count. ECF No. 94 at 5; see also ECF No. 96 at 156 (respondent’s expert indicating that
“the HPV sequences [did not] stimulate the T cell clones”). Petitioner does not seriously
contest that finding. Instead, petitioner focuses on the special master’s treatment of the
Kanduc article. ECF No. 99 at 27-28.
The special master discounted the Kanduc article. In his view, the “various
problems” identified by Kanduc as resulting from cross-reactivity do not “resemble the
problems that appear in MS.” ECF No. 94 at 5. According to petitioner, Kanduc
described “82 perfect overlaps between HPV16 and the human proteome, any of which
could trigger autoimmunity in a predisposed individual.” ECF No. 99 at 28. The special
master treated these overlaps as “possible” scenarios for cross-reactivity, but not as a
“reliable basis for elevating this potentiality to a probability.” ECF No. 94 at 5.
Before reaching this conclusion, the special master heard testimony on petitioner’s
theory from her expert during the evidentiary hearing. See ECF No. 96 at 57-60
(discussing molecular mimicry in the context of MS and discussing the Wucherpfennig
and Kanduc articles). Petitioner’s expert testified at several points during the hearing that
that the HPV vaccine has the potential to trigger MS. See, e.g., id. at 97 (stating that the
HPV vaccine “can potentially” trigger MS, but also stating that he advises his MS
patients to get vaccines); id. at 99 (noting, with regard to the Wucherpfennig article, that
“one of the things that I kind of garner from the article is that there is the potential that
activated T cell clones can autoreact against proteins on HPV”); id. at 99-100 (“[O]ne of
the important points I thought about . . . Wucherpfennig is that it may not have the most
robust response, . . . but there is the potential that it could.”); id. at 129 (acknowledging
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that the Kanduc article does not state “that the HP[V] vaccine can cause MS”); id. at 131-
32 (petitioner’s expert stating that he has not “been able to provide any studies that
demonstrate a causal relationship between the HPV vaccine and MS,” but has offered
studies that “it can create an autoimmune response”).
After explaining at considerable length the framework of his analysis, the special
master concluded that petitioner’s evidence of an exacerbated injury due to molecular
mimicry was insufficient. In reference to petitioner’s expert’s testimony, the special
master explained at the October 1, 2018 evidentiary hearing, as follows:
[O]n some level you can’t say that to say there is potential reaction is
erroneous because you could always say there is a potential for a reaction,
but . . . I think the . . . potentiality is not the same thing as meeting a
preponderance of the evidence.
Id. at 245. In his written decision, the special master held that petitioner “has provided
no reliable basis for elevating the potentiality [of molecular mimicry] to a probability.”
ECF No. 94 at 5.
In the court’s view, the special master did not err in his consideration of the
molecular mimicry theory. Petitioner’s objection to his analysis is more a disagreement
with his exercise of discretion than the identification of legal error. Petitioner argues that
the special master “discount[ed] the evidence supporting her theory and, instead,
require[d] direct proof of petitioner’s proffered mechanism.” ECF No. 99 at 30. The
record does not support this position. The special master conducted a lengthy colloquy
with petitioner’s expert, reviewed the articles petitioner’s expert presented on the subject,
and specifically stated that he considered all of the evidence presented before reaching
his decision. The court cannot accept petitioner’s invitation to reweigh the evidence. See
Porter v. Sec’y of Health & Human Servs., 663 F.3d 1242, 1249 (Fed. Cir. 2011) (stating
that the reviewing court does not “reweigh the factual evidence, assess whether the
special master correctly evaluated the evidence, or examine the probative value of the
evidence or the credibility of the witnesses—these are all matters within the purview of
the fact finder”) (citations omitted).
For these reasons, petitioner’s motion for review must be denied, and the special
master’s decision denying compensation must be affirmed.
IV. Conclusion
For the above-stated reasons, the court sustains the entitlement decision of the
special master. Accordingly, it is hereby ORDERED that:
(1) Petitioner’s motion for review, ECF No. 97, is DENIED;
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(2) The decision of the special master, filed October 5, 2018, is SUSTAINED;
(3) The clerk’s office is directed to ENTER final judgment in accordance with
the special master’s decision of October 5, 2018; and
(4) The parties shall separately FILE any proposed redactions to this opinion,
with the text to be redacted clearly blacked out, on or before March 26,
2019.
IT IS SO ORDERED.
s/Patricia E. Campbell-Smith
PATRICIA E. CAMPBELL-SMITH
Judge
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