Abstract
Background.
While positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (FDG) is most commonly used for imaging malignant tumors, vaccination is known to cause transient inflammation of lymph nodes inducing positive findings on FDG-PET scans. The pattern, magnitude and duration of lymph node activation following vaccination have not been clearly defined. Furthermore, the addition of adjuvants to vaccines can further enhance the immune response. The presented study was designed to define lymph node activation following administration of the Food Drug Administration (FDA) licensed human papillomavirus (HPV) vaccines, Cervarix® and Gardasil®, which contain similar antigens with different adjuvants.
Methods.
Twenty seven women ages 18–25 were randomized to receive either Cervarix® or Gardasil® in the clinical trial VRC 900. Fifteen subjects participated the PET/CT scan portion of the trial and received scans of lymph node activation at pre vaccination and “one week” (8 to 14 days) and “one month” (23 to 36 days) after first or third vaccination.
Results.
PET/CT scans revealed that all vaccine recipients had ipsilateral axillary lymph node activity. Three out of four Cervarix® recipients also showed contralateral lymph node activity one month after first vaccination. For both Cervarix® and Gardasil® the standardized update value (SUV) activity resolved over time, with activity extended up to to day 37 post first and third vaccination.
Conclusions.
Following intramuscular vaccination there were no major differences between duration of uptake and intensity of SUV between Cervarix® and Gardasil® recipients in ipsilateral axillary lymph nodes. Contralateral node activation was detected up to one month post first vaccination in Cervarix® recipients only; possibly reflecting differences in vaccine adjuvant formulation.
Keywords: PET/CT, SUV, FDG, Human Papillomavirus Vaccination
INTRODUCTION
Positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (FDG) is most commonly used for imaging malignant tumors. The combination of FDG PET with in-line computer tomography (CT) systems for tumor localization has made PET/CT very common for detection and follow-up of malignancies. FDG is a glucose analogue which becomes trapped within metabolically active cells. Increased glycolic rate in tumors as compared to physiologic cells is the bases for its use in PET imaging. It has also been shown that FDG can also accumulate in benign conditions such as inflammation and infection, leading to false positive interpretations for malignant tumors in PET/CT scans. 1 Influenza vaccination is known to cause transient inflammation of lymph nodes inducing positive findings on FDG-PET scans. 2–5 Furthermore, adjuvants, used to increase immunogenicity of a vaccine, can enhance antibody response and potentially inflammation. 6
Understanding how benign changes such as lymph node activation following vaccination may affect interpretation of PET scan results is important for prevention of false positive scan results. In the presented work we report the results of FDG-PET scans at baseline and following immunization of healthy volunteers with two Food and Drug Administration (FDA) approved human papillomavirus (HPV) vaccines, Cervarix® (GlaxoSmithKline) and Gardasil® (Merck). Cervarix® and Gardasil® are both virus-like particle (VLP) vaccines that deliver similar antigens but contain different adjuvants. The Gardasil® vaccine is adjuvanted with aluminum salts. The Cervarix® vaccine is formulated with ASO4, which contains aluminum hydroxide salts and a TRL 4 agonist, MPL (3-O-desacyl-4’-monophosphoryl lipid A). The ASO4 Cervarix® adjuvant has been implicated in inducing higher antibody titers and cross protection in non-vaccine HPV subtypes, 7–11 however is unclear if these results can be solely attributed to adjuvant formulation 12.
In the present study, manufacturer instructions were followed for each vaccine in a series of threeimmunizations, Cervarix® or Gardasil® (months 0, 1, 6 or months 0, 2, 6, respectively). Each subject received three PET/CT scans surrounding either their first or third vaccination in the series: pre-vaccine, ‘one week’ (8–14 days) post-vaccine, and ‘three weeks’ (23 to 36 days) post-vaccine. There are limited reports of other studies that have scanned patients at various time points post influenza vaccination 4, 5, 13. This is the first immunization study to follow the same individual pre-vaccination and at two distinct time points post vaccination. The presented work is also the first study to report on lymph node activation duration following HPV immunization. Lymph node activation is measured semi-quantitatively by FDG uptake reported with standardized uptake values (SUV). There is currently a lack of clarity regarding the expected magnitude of SUVs following vaccination in activated lymph nodes. Here we provide reference SUV values and duration of response following HPV vaccination. The presented study was designed to identify the duration and magnitude of lymph node activation in response to a commonly administered vaccine to aid in evaluation of potential false positive PET scans and provide understanding of the immune response. This work should aid in the interpretation of PET scan results from recent vaccination that have the potential to lead to unnecessary biopsies, additional PET scans, and altered treatment. This lymph node activation data can also be used to correlate with immune response measurements and inform future vaccine design.
SUBJECTS AND METHODS
Study Design and Participants.
Women were enrolled into a National Institute of Allergy and Infectious Diseases (NIAID), Vaccine Research Center (VRC) clinical trial, VRC 900, at the National Institutes of Health (NIH) Clinical Center, Bethesda, Maryland, USA (ClinicalTrials.gov #NCT01132859). The study was reviewed and approved by the NIAID Institutional Review Board. The study team followed human experimental guidelines for conducting clinical research from the US Department of Health and Human Services.
Twenty-seven women ages 18 years to 25 were enrolled in VRC 900 and randomized in a 1:1 ratio to receive either the Cervarix® or Gardasil® 3 injection regimen (months 0, 1, 6 or months 0, 2, 6, respectively) as per package insert (open label) recommendations for vaccination. Subjects underwent a pre-vaccination assessment of general health, blood draw, and pregnancy test for baseline assessment. Additional trial design details, including Consolidated Standards of Reporting Trials (CONSORT) diagram and subject demographics, have been previously published. 11
PET/CT Scans.
Of the 27 subjects enrolled in the VRC 900 trial, 15 participated in PET scans portion of the trial. These 15 subjects received scans surrounding either first or third vaccinations. Metabolic activity was assessed pre and post first (Cervarix® n=4, Gardasil® n=4) or third vaccination (Cervarix® n=4, Gardasil® n=3). Post vaccination PET/CT scans were performed at “one week” (8 to 14 days) and “one month” (23 to 36 days) post vaccination. A sequence of three PET/CT scans were performed in each patient: prior to first or third vaccine administration; 8 to 14 days following first or third vaccine administration; and 23 to 36 days after first or third vaccine administration. The majority of scans were conducted on a hybrid PET/CT scanner Siemens mCT (64 slices) and a GE Discovery PET Advanced scanner (16 slices) was used in select cases when the PET/CT scanner was unavailable. The CT was performed using a tube current of only 35 mA intending a low radiation dose to the patient and used for attenuation correction and image localization. Patients fasted for at least 6 hours prior to scanning. Blood glucose levels were lower than 150 mg/dl in all patients. According to the protocol, 60 min after intravenous administration of 18F-FDG (Cardinal Health) PET/CT images were acquired in 3D mode with the Siemens PET/CT (3 min/bed position) and 2D mode (5 min/bed position) with the GE PET/CT, covering the base and the skull, neck, thorax, abdomen and pelvis, with arms raised above the head. The images were reconstructed using OSEM algorithm (4 iterations/30 subsets) for the GE PET/CT and iterative reconstruction (3 iterations/24 subsets) for the Siemens PET/CT. PET images, CT images, and fused PET/CT images were reviewed on a dedicated workstation and interpreted by a board certified nuclear medicine physician. Maximum standard uptake value (SUVmax), as a ratio of the tissue radioactivity concentration to the total injected activity per patient’s body weight, was reported for lymph nodes with perceptible metabolic activity. The number of activated lymph nodes was also recorded.
RESULTS
Both Cervarix® and Gardasil® are highly immunogenic vaccines, and all subjects in this trial had high antibody titers to both delivered vaccines. 11
Metabolic Activity at Lymph Nodes by PET/CT.
Lymph node activity was measured by standard uptake value (SUV). SUV should represent inflammation, antigen processing, and cell proliferation/apoptosis. PET/CT scans were conducted pre and post vaccination at “one week” and “one month” at either first or third vaccination. All subjects showed ipsilateral node uptake of FDG in the axillary draining lymph node (DLN) node one week post first and third vaccinations.
PET/CT Patterns Surrounding First Vaccination.
Based on site of vaccination, at “one week” the range of SUV for Cervarix® (n=4) was 2.7 to 5.4 with 1 to 6 nodes activated (Table 1) and the range of SUV for Gardasil® (n=4) was 2.5 to 8.7 with 1 to 2 nodes activated (Table 2). At “one month” 3 of 4 Cervarix® (SUV 2.5 to 3.7, 3 to 5 nodes, Table 1) and 2 of 4 Gardasil® recipients (SUV 4.4 to 8.8, 2 to 4 nodes, Table 2) showed metabolic activity in the ipsilateral axillary node. Vaccination with Cervarix® not only produced localized and ipsilateral lymph activity, but three subjects also showed contralateral activity. One subject showed contralateral activity at “one week,” however it was consistent with this subject’s baseline reference SUV value and location (Table 1). At “one month” two subjects showed contralateral axillary lymph node activity (SUV 2.1 to 2.6, 1 to 4 nodes) and the third subject demonstrated contralateral head and neck lymph node activation (SUV 4.1, 1 node) (Figure 1, Table 1). There was no contralateral head/neck or axillary nodal activity in recipients of Gardasil® at either time point following first vaccination (Figure 2, Table 2).
Table 1:
Lymph Node activation surrounding first vaccination with Cervarix®
| Cervarix® 1st Series ‘One Week’ Post 1st Vaccination | |||||||
|---|---|---|---|---|---|---|---|
| Subject ID | Vaccination Site | Days After Vaccination | Axilla | Head/Neck SUV and Location | Ipsilateral SUV, Location, Number of Nodes | Contralateral SUV, Location, Number of Nodes | Reference SUV, Location, Number of Nodes |
| 002 | L | 10 | L only | - | 2.7*, L axilla, 3 | - | - |
| 019 | L | 8 | L only | 1 L & 4.8 R | 5.4*, L axilla, 6 | - | - |
| 023 | R | 9 | R only | - | 3.7*, R axilla, 1 | - | - |
| 026 | R | 14 | L & R | - | 4.6*, R axilla, 3 | 1.6, L axilla, 2 | 1.6, L axilla, 3 |
Denotes SUVmax value
Table 2:
Lymph Node activation surrounding first vaccination with Gardasil®
| Gardasil® 1st Series ‘One Week’ Post 1st Vaccination | ||||||
|---|---|---|---|---|---|---|
| Subject ID | Vaccination Site | Days After Vaccination | Axilla | Ipsilateral SUV, Location, Number | Contralateral Axilla SUV | Reference SUV, Location, Number of Nodes |
| 003 | L | 9 | L only | 2.5*, L axilla, 1 | - | - |
| 008 | L | 9 | L only | 2.8*, L axilla, 1 | - | - |
| 012 | L | 8 | L only | 5.1*, L axilla, 2 | - | 1.4, L axilla, 1 |
| 029 | L | 14 | L only | 8.7*, L axilla, 2 | - | - |
Denotes SUVmax value
Figure 1.
PET/CT scan of subject 019 (Cervarix®) ‘one month’ post first vaccination with contralateral head/neck node activation SUVmax 4.1 (arrow). Image is attenuation corrected (AC) and was acquired in a 5 minute frame 60 minutes post injection.
Figure 2.
PET/CT scan of subject 029 (Gardasil®) ‘one month’ posted first vaccination with ipsilateral axilla node activation SUVmax 8.8 (arrow). Image is attenuation corrected (AC) and was acquired in a 5 minute frame 60 minutes post injection.
In Cervarix® recipients the total number of activated nodes ranged from 1–6 at “one week” and 1–5 at “one month” following first vaccination (table 1). In Gardasil® recipients the total number of activated nodes ranged from 1–2 at “one week” and 2–4 at “one month” following first vaccination (table 2).
Both vaccines show durability of node activation over time. In Cervarix® recipients 4 out of 4 subjects continue to show node activation 23–37 days post vaccination (SUV range 2.1 – 4.1, 1–5 nodes). Of these subjects, 2 out of 4 subjects had contralateral axillary nodes showing uptake in final PET scan (Figure 3, Table 1). Following a single dose of Gardasil, 2 out of 4 subjects showed ispilateral node activation 30–31 days post vaccination (SUV range 1.4 – 8.8, 2–4 nodes) (Figure 3, Table 2).
Figure 3.
Node activation over time following first and third vaccinations of Cervarix® and Gardasil®. A) SUV ipsilateral nodes, B) SUV contralateral nodes and C) SUVmax.
PET/CT Patterns Surrounding Third Vaccination.
All subjects received two vaccinations in one arm, either the first two or the first and last vaccination (i.e R, L, R or R, R, L, etc.). The reported node orientations are based on the site of the third vaccination. At “one week” Cervarix® recipients (n=4) showed ipsilateral lymph node activation with an SUV range from 1.3 to 3.9 and 1 to 2 activated nodes (Table 3). Gardasil® recipients (n=3) had ipsilateral SUV range of 1.4 to 12 with 1 to 6 activated nodes (Table 4). By “one month” 33% of Cervarix® subjects and 66% of Gardasil® recipients showed ipsilateral activity (Figure 4,5 & Table 3, 4). No major differences were observed in ipsilateral node activation of the two vaccine groups following third vaccination.
Table 3:
Lymph Node activation surrounding third vaccination with Cervarix®
| Cervarix® 2nd Series ‘One Week’ Post 3rd Vaccination | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subject ID | Vaccination (Vax) Site | Axilla | Days Between 1st and 2nd Vax | Days Between 2nd and 3rd Vax | Days Post 3rd Vax | Reference SUV Pre-3rd Vaccination, Location, Number of Nodes | Head/ Neck SUV, Location, Number of Nodes | Ipsilateral SUV, Location, Number of Nodes | Contralateral SUV, Location, Number of Nodes |
| 030 | L R L | L & R | 29 | 130 | 8 | - | - | 2.1*, L axilla, 2 | 1.3, R axilla, 1 |
| 034 | R R L | L & R | 28 | 140 | 8 | 1.8, R axilla, 4 | - | 2.2*, L axilla, 2 | 1.8, R axilla, 2 |
| 035 | R L L | L only | 37 | 131 | 8 | - | 1, L, 1 | 3.5*, L axilla, 2 | - |
| 037 | L L R | R only | 28 | 140 | 7 | - | - | 3.9*, R axilla, 2 | - |
Denotes SUVmax value
Table 4:
Lymph Node activation surrounding third vaccination with Gardasil®
| Subject ID | Vaccination (vax) Site | Axilla | Days Between 1st and 2nd Vax | Days Between 2nd and 3rd Vax | Days Post 3rd Vax | Reference SUV Pre-3rd Vaccination, Location, Number of Nodes | Ipsilateral SUV, Location, Number of Nodes | Contralateral SUV, Location, Number of Nodes |
|---|---|---|---|---|---|---|---|---|
| 017 | L R L | L only | 50 | 119 | 8 | - | 1.4*, L axilla, 1 | - |
| 027 | L L R | L & R | 58 | 110 | 7 | 2.1, L axilla, 1 | 1.9, R axilla, 1 | 2.1*, L axilla, 1 |
| 031 | R R L | L & R | 56 | 112 | 8 | 2.3, L axilla,1 3.5, R axilla, 4 |
12*, L axilla, 6 | 3, R axilla, 1 |
Denotes SUVmax value
Figure 4.
PET/CT scan of subject 035 (Cervarix®) ‘one month’ post third vaccination with ipsilateral node activation SUVmax 1.7 (arrow). Image is attenuation corrected (AC) and was acquired in a 5 minute frame 60 minutes post injection
Figure 5.
PET/CT scan of subject 031 (Gardasil®) ‘one month’ posted third vaccination with ipsilateral axilla node activation SUVmax 4.7 (arrow). Image is attenuation corrected (AC) and was acquired in a 5 minute frame 60 minutes post injection.
Recipients of Cervarix® and Gardasil® also displayed comparable ipsilateral and contralateral responses following third vaccination. Two of four recipients of Cervarix® and two of three recipients of Gardasil® showed SUV activity in contralateral lymph nodes ‘one week’ after third vaccination (Table 3,4). ‘One month’ following third vaccination one Gardasil® recipient continued to show contralateral node activation.
In Cervarix® recipients the total number of activated nodes ranged from 1–4 at “one week” and 1 at “one month” following third vaccination (Table 1). In Gardasil® recipients the total number of activated nodes ranged from 1–6 at “one week” and 1–3 at “one month” following third vaccination (Table 4).
Both vaccines showed some durability of node activation over time following third vaccination. In Cervarix® recipients 1 out of 4 showed ipsilateral node activation at ‘one month’ (37 days) post vaccination (SUV 1.7, 1 node) (Figure 3, Table 3). Following the third vaccination of Gardasil®, 2 out of 3 subjects showed ispilateral node activation ‘one month’ (35–37) days post vaccination (SUV range 13.7 – 4.7, 1–3 nodes) (Figure 3, Table 4).
DISCUSSION
Metabolic activity in the draining lymph nodes (DLN) is consistent with development of an immune response post vaccination 3, 5, 14, 15. There have been attempts to describe the effect of vaccination on lymph nodes by PET scan and small case studies of lymph node activation post injection of the influenza vaccine have been reported.3, 5, 16 Normally, the contralateral node is used as a baseline value and administration of a single dose vaccine in the deltoid muscle will produce localized and ipsilateral axillary SUV activity that peaks after vaccination and resolves with time. 2, 13, 16–19. However, there have been no prospective studies that examined lymph node activity pre and post vaccination with positron emission tomography/computerized tomography (PET/CT) to aid in identification of node activation time and location. We investigated PET/CT activity at pre vaccination, post vaccination at “one week” (8 to 14 days) and “one month” (23 to 36 days) after first or third vaccination with the FDA licensed HPV vaccines Cervarix® and Gardasil®.
Cervarix® and Gardasil® are both highly immunogenic and effective and contain similar antigenic content but with different adjuvants (AS04 and aluminum salts, respectively) and we designed a prospective assessment of lymph node activity by PET/CT comparing these two vaccines. Both vaccines were highly immunogenic in all subjects and the response was significant even after the initial vaccination in each regimen. 11 Overall, there was no major difference between duration of uptake and intensity of SUV between Cervarix® and Gardasil® recipients. For either Cervarix® or Gardasil® the SUV activity extended to day 36 of first vaccination and day 37 post third vaccination. One possible difference observed between vaccines was related to location of lymph node activity: only recipients of Cervarix® had contralateral SUV activity at both “one week” and “one month” following first vaccination, where Gardasil® recipients showed only ispilateral node activation. The same distinction was not observed following third vaccination, however, it should be noted that by third vaccination all recipients had received vaccine administration in both left and right arms.
We demonstrate here that axillary nodes remain activated and detectable by PET/CT scan up to 37 days post vaccine administration. We also show that contralateral node activation can be detected up to one month post vaccination and therefore may not be suitable as a baseline control during vaccine administration. Importantly we did not observe vaccination induced lymph node activity proximal or distal to the axillary lymph nodes and thus provide evidence that lymph node activation beyond one month or outside of the axillary region should not be contributed to vaccination without consideration and evaluation for other causes.
| Cervarix® 1st Series ‘One Month’ Post 1st Vaccination | |||||
|---|---|---|---|---|---|
| Subject ID | Axilla | Days After Vaccination | Ipsilateral SUV, Location, Number of Nodes | Contralateral SUV, Location, Number of Nodes | Percent Change Max. SUV Week One to Week Three |
| 002 | L & R | 30 | 2.5*, L axilla, 5 | 2.1, R axilla, 4 | 7.4% decrease |
| 019 | - | 23 | - | 4.1*, R head/neck, 1 | 14.6% decrease |
| 023 | R | 37 | 3.7*, R axilla, 3 | no change | |
| 026 | L & R | 28 | 2.7*, R axilla, 3 | 2.6, L axilla, 1 | 41.3% decrease R axilla 62.5% increase L axilla |
Denotes SUVmax value
| Gardasil® 1st Series ‘One Month’ Post 1st Vaccination | |||||
|---|---|---|---|---|---|
| Subject ID | Axilla | Days After Vaccination | Ipsilateral SUV, Location, Number of Nodes | Contralateral SUV, Location, Number of Nodes | Percent Change Max. SUV Week One to Week Three |
| 003 | - | 31 | - | - | - |
| 008 | - | 36 | - | - | - |
| 012 | L | 30 | 4.4*, L axilla, 4 | - | 13.725% decrease |
| 029 | L | 31 | 8.8*, L axilla, 2 | - | 1.2% increase |
Denotes SUVmax value
| Cervarix® 2nd Series ‘One Month’ Post 3rd Vaccination | |||||
|---|---|---|---|---|---|
| Subject ID | Axilla | Days Post 3rd Vax | Ispilateral SUV, Location, Number of Nodes | Contralateral Axilla SUV | Percent Change From Max SUV at One Week |
| 030 | |||||
| 034 | - | 36 | - | ||
| 035 | L | 37 | 1.7*, L axilla, 1 | - | 56.4% decrease |
| 037 | - | 36 | - | - | |
Denotes SUVmax value
| Gardasil 2nd Series ‘One Month’ Post 3rd Vaccination | |||||
|---|---|---|---|---|---|
| Subject ID | Axilla | Days Post 3rd Vax | Ispilateral SUV, Location, Number of Nodes | Contralateral Axilla SUV, Number of Nodes | Percent Change From Max SUV at One Week |
| 017 | L | 35 | 3.7*, L axilla, 3 | - | 264% increase |
| 027 | - | 56 | - | - | - |
| 031 | L & R | 37 | 4.7*, L axilla, 1 | 2.1 R, 1 | 60% decrease L axilla, |
Denotes SUVmax value
Acknowledgements.
The authors thank the vaccine trial volunteers for their contribution and commitment to vaccine research. We also acknowledge the contributions of our NIH Clinical Center and NIAID colleagues, NIAID Institutional Review Board, the EMMES Corporation, and colleagues at the NIAID Vaccine Research Center and the National Cancer Institute. The findings and conclusions in this report are those of the authors and do not necessarily reflect the views of the funding agency or collaborators.
The VRC 902 Study Team includes Mary E Enama, Ingelise Gordon, Sarah Plummer, Cynthia Starr Hendel, Laura Novik, Kathy Zephir, Floreliz Mendoza, Jamie Saunders, Nina Berkowitz, Brandon Wilson, Tanya Clarke, Sandra Sitar, Brenda Larkin, Joseph Casazza, Sheryl Young, Leejah Chang, Olga Vasilenko, Iris Pittman, Hope Decederfelt, LaChonne Stanford, and Robert T. Bailer.
Funding.
This study was funded by the National Institutes of Health, National Institutes Intramural Research Program. ClinicalTrials.gov #NCT01132859
Footnotes
Conflicts of Interest. The authors declare that we have no conflicts of interest.
References
- 1.Stumpe KD, Dazzi H, Schaffner A, et al. Infection imaging using whole-body FDG-PET. Eur J Nucl Med. 2000;27:822–832. [DOI] [PubMed] [Google Scholar]
- 2.Williams G, Joyce RM, Parker JA. False-positive axillary lymph node on FDG-PET/CT scan resulting from immunization. Clinical Nuclear Medicine. 2006;31:731–732. [DOI] [PubMed] [Google Scholar]
- 3.Panagiotidis E, Exarhos D, Housianakou I, et al. FDG uptake in axillary lymph nodes after vaccination against pandemic (H1N1). European Radiology. 2010;20:1251–1253. [DOI] [PubMed] [Google Scholar]
- 4.Thomassen A, Lerberg Nielsen A, Gerke O, et al. Duration of 18F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination. Eur J Nucl Med Mol Imaging. 2011;38:894–898. [DOI] [PubMed] [Google Scholar]
- 5.Burger IA, Husmann L, Hany TF, et al. Incidence and Intensity of F-18 FDG Uptake After Vaccination With H1N1 Vaccine. Clinical Nuclear Medicine. 2011;36:848–853. [DOI] [PubMed] [Google Scholar]
- 6.Brown LE. The role of adjuvants in vaccines for seasonal and pandemic influenza. Vaccine. 2010;28:8043–8045. [DOI] [PubMed] [Google Scholar]
- 7.Einstein MH, Baron M, Levin MJ, et al. Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18–45 years. Hum Vaccin. 2009;5:705–719. [DOI] [PubMed] [Google Scholar]
- 8.Draper E, Bissett SL, Howell-Jones R, et al. A Randomized, Observer-Blinded Immunogenicity Trial of Cervarix (R) and Gardasil (R) Human Papillomavirus Vaccines in 12–15 Year Old Girls. Plos One. 2013;8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Malagon T, Drolet M, Boily MC, et al. Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infectious Diseases. 2012;12:781–789. [DOI] [PubMed] [Google Scholar]
- 10.Giannini SL, Hanon E, Moris P, et al. Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine. 2006;24:5937–5949. [DOI] [PubMed] [Google Scholar]
- 11.Herrin DM, Coates EE, Costner PJ, et al. Comparison of adaptive and innate immune responses induced by licensed vaccines for Human Papillomavirus. Hum Vaccin Immunother. 2014;10:3446–3454. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Schiller JT, Castellsague X, Garland SM. A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines. Vaccine. 2012;30:F123–F138. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Shirone N, Shinkai T, Yamane T, et al. Axillary lymph node accumulation on FDG-PET/CT after influenza vaccination. Annals of Nuclear Medicine. 2012;26:248–252. [DOI] [PubMed] [Google Scholar]
- 14.Iyengar S, Chin B, Margolick JB, et al. Anatomical loci of HIV-associated immune activation and association with viraemia. Lancet. 2003;362:945–950. [DOI] [PubMed] [Google Scholar]
- 15.Kline RM. PET scan hypermetabolism induced by influenza vaccination in a patient with non-Hodgkin lymphoma. Pediatric Blood & Cancer. 2006;46:389–389. [DOI] [PubMed] [Google Scholar]
- 16.Thomassen A, Nielsen AL, Gerke O, et al. Duration of F-18-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination. European Journal of Nuclear Medicine and Molecular Imaging. 2011;38:894–898. [DOI] [PubMed] [Google Scholar]
- 17.Jones RL, Cunningham D, Cook G, et al. Tumour vaccine associated lymphadenopathy and false positive positron emission tomography scan changes. British Journal of Radiology. 2004;77:74–75. [DOI] [PubMed] [Google Scholar]
- 18.Focosi D, Caracciolo F, Galimberti S, et al. False positive PET scanning caused by inactivated influenza virus vaccination during complete remission from anaplastic T-cell lymphoma. Annals of Hematology. 2008;87:343–344. [DOI] [PubMed] [Google Scholar]
- 19.Sheehy N, Drubach L. F-18-Fdg Uptake at Vaccination Site. Pediatric Radiology. 2008;38:246–246. [DOI] [PubMed] [Google Scholar]