0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
The Cutting Edge |

Recalcitrant Cutaneous Warts Treated With Recombinant Quadrivalent Human Papillomavirus Vaccine (Types 6, 11, 16, and 18) in a Developmentally Delayed, 31-Year-Old White Man FREE

Supriya S. Venugopal, MBBS, BSc, M Med; Dedee F. Murrell, MA, BM, MD, FAAD
[+] Author Affiliations

Section Editor: Erik J. Stratman, MD
Assistant Section Editor: William D. Aughenbaugh, MD
Assistant Section Editor: Michael P. Heffernan, MD

More Author Information
Arch Dermatol. 2010;146(5):475-477. doi:10.1001/archdermatol.2010.71.
Text Size: A A A
Published online

A 31-year-old white man with developmental delay and a history of epilepsy was seen in February 2008 with multiple warts on his hands that had been present for several years. He had previously been treated with podophyllin, 2 different concentrations of salicylic acid (25% and 40%), and oral cimetidine, and his regular medications included lamotrigine, valproate, topiramate, and levetiracetam. He denied other risk factors for human immunodeficiency virus (HIV) or AIDS and lived at home with his parents. He also denied a history of other autoimmune conditions and allergies and had no relevant family history of other illnesses or dermatologic conditions.

On examination, we found that he had multiple hyperkeratotic warty lesions on the dorsal and palmar aspects of his hands bilaterally (Figure 1). In addition, he had multiple warts on his chin, both knees, and right third metatarsophalangeal joint. In total, he had about 30 warts, the largest of which was on the right thumb.

Place holder to copy figure label and caption
Figure 1.

Prevaccine dorsal aspect of both hands. The right hand shows warts on the thumb periungually and index finger over the proximal interphalangeal joint and periungually. The left hand shows warts on the left thumb and left index finger.

Graphic Jump Location

Several additional treatments were tried, including cryotherapy and 6 weeks of nightly application of imiquimod cream. We considered acitretin therapy, but this was not initiated owing to his neurologists' concerns about potential interactions with his antiepileptic medications.

Owing to the persistence and extensive nature of the warts, we performed a complete blood cell count; tests for electrolyte, urea, creatinine, and fasting glucose levels; liver function tests; thyroid function tests; and an HIV screen, the results of which were all normal. No human papillomavirus (HPV) typing was performed. A genetic underlying immune deficiency was thought to be very unlikely, given his relatively older age at presentation. The patient denied having a sexual partner, and no genital warts were found on examination. The patient and his family also denied a history of genital warts.

Based on anecdotal evidence of treatment of warts with Gardasil (CSL Biotherapies, Melbourne, Australia), a recombinant quadrivalent HPV vaccine, the patient was prescribed the vaccine to be injected into his arm by his family practitioner in 3 doses at 0, 2, and 6 months.

The patient returned for review 4 weeks, 18 weeks, 8 months, and 18 months after his initial examination and pretreatment with the vaccine. Four weeks after the first injection, the warts had improved substantially, particularly on his hands and knees. Ten weeks after his second injection, further substantial remission of several warts was noted. Approximately 4 months after commencement of the vaccine injections, there was more improvement and further regression of his warts. The areas substantially affected by cutaneous warts prior to vaccine administration, such as his hands, showed complete regression at 8 months (Figure 2). By 8 months, the patient showed complete regression of all 30 of his warts, and almost 18 months after the initial treatment with the vaccine, the patient was still free of all warts. No additional treatments were used during the follow-up period, and no warts were present 18 months after his initial treatment with the vaccine.

Place holder to copy figure label and caption
Figure 2.

Eight months after commencing treatment with arm injections of a recombinant quadrivalent human papillomavirus vaccine, the hands were free of all the warts.

Graphic Jump Location

Human papillomavirus is associated with cervical and vulvovaginal cancers, genital warts, and precancerous dysplasia. Several studies have confirmed the role of a prophylactic quadrivalent HPV vaccine (HPV types 6, 11, 16, and 18) in the prevention of HPV-associated precancerous and cancerous lesions.15 The quadrivalent, inactivated HPV vaccine has been shown to be from 95% to 100% effective in the prevention of HPV-6–, -11–, -16–, and -18–related cervical and genital disease in young, HPV-naive women aged between 16 and 26 years. The quadrivalent HPV vaccine had a protective effect against neoplasia in women testing positive for HPV-1 through -3. This vaccine is now routinely recommended for female patients aged between 11 and 26 years. The vaccination schedule involves the administration of 3 injections at baseline, 2 months, and 6 months.

While many studies have concluded that HPV vaccines are highly efficacious in the prevention of genital HPV infection, there have been no clinical trials done to specifically address whether the HPV-16 vaccines can treat multiple common warts; this has been addressed only peripherally in other trials of the HPV vaccine for genital HPV and/or cervical cancer.15 Recently, Albarran Y Carvajal and colleagues6 published the results of a phase 1 and 2 study investigating MVA E2 recombinant vaccine (modified vaccinia vaccine Ankara expressing the E2 gene of bovine papilloma virus) in the treatment of HPV infections in men with intraurethral flat condyloma. The vaccine was administered directly into the urethra weekly for 4 weeks, and 28 of the 30 men showed complete remission of the condyloma.6

It is important to note that spontaneous regression of warts independent of the vaccine injection can occur. Human papillomavirus vaccines have been shown to provide cross-protection against other strains that are related.710 We report herein a case of complete remission of highly recalcitrant cutaneous warts 8 months after commencing vaccine injections in the usual manner.

Treatments for HPV infection may include salicylic acid, trichloroacetic acid, bichloroacetic acid, cryotherapy, podophyllin resin, podophyllotoxin, imiquimod, carbon dioxide laser, and surgical techniques. A published report has documented remission of genital warts in patients after administration of the MVA E2 vaccine,6 but current guidelines support the use of the vaccine for prevention of infection.15 The present case highlights the potential use of the vaccine for the treatment of extensive common warts. There might be some cross-reactivity of antigenic epitopes in the HPV types covered by the vaccine and other HPV types responsible for common warts. Since patients with multiple warts are often in the preteen or young teenage category, there could be a double benefit in prescribing wart virus vaccines to such patients. Boys given the vaccine prior to sexual activity would reduce their chance of developing genital warts in the first place.

Complete remission of cutaneous warts after recombinant quadrivalent HPV vaccine administration has not been reported previously, to our knowledge, and the present case suggests that a prospective randomized controlled trial of the vaccine would be worthwhile to conduct in otherwise healthy patients with multiple, recalcitrant hand, plantar, or even genital warts. The trials thus far have had as their primary outcome measure cervical cancer, and patients with warts have only incidentally been included. Hence, there have been no placebo-controlled randomized controlled trials of this vaccine for the elimination of warts.Article

Correspondence: Dedee F. Murrell, MA, BM, MD, FAAD, Department of Dermatology, St George Hospital, University of New South Wales, Kogarah, Sydney, New South Wales 2217, Australia (d.murrell@unsw.edu.au).

Accepted for Publication: January 12, 2010.

Author Contributions: Both authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Murrell. Acquisition of data: Venugopal and Murrell. Analysis and interpretation of data: Venugopal. Drafting of the manuscript: Venugopal. Critical revision of the manuscript for important intellectual content: Venugopal and Murrell. Administrative, technical, and material support: Murrell. Study supervision: Murrell.

Financial Disclosure: None reported

Additional Contributions: The patient and his parents assisted with this study.

Submissions

Clinicians, residents, and fellows are invited to submit cases of challenges in management and therapeutics to this section. Cases should follow the established pattern. Manuscripts should be prepared double-spaced with right margins nonjustified. Pages should be numbered consecutively with the title page separated from the text (see Instructions for Authors [http://archderm.ama-assn.org/misc/ifora.dtl] for information about preparation of the title page). Clinical photographs, photomicrographs, and illustrations must be sharply focused and submitted as separate JPG files with each file numbered with the figure number. Material must be accompanied by the required copyright transfer statement (see authorship form [http://archderm.ama-assn.org/misc/auinst_crit.pdf]). Preliminary inquiries regarding submissions for this feature may be submitted to Erik J. Stratman, MD (stratman.erik@marshfieldclinic.org). Manuscripts should be submitted via our online manuscript submission and review system (http://manuscripts.archdermatol.com).

Villa  LLCosta  RLPetta  CA  et al.  High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer 2006;95 (11) 1459- 1466
PubMed
FUTURE II Study Group, Prophylactic efficacy of a quadrivalent human papillomavirus (HPV) vaccine in women with virological evidence of HPV infection. J Infect Dis 2007;196 (10) 1438- 1446
PubMed
Markowitz  LEDunne  EFSaraiya  M  et al. Advisory Committee on Immunization Practices (ACIP), Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007;56 (RR-2) 1- 24
PubMed
Schiller  JTCastellsagué  XVilla  LLHildesheim  A An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Vaccine 2008;26 ((suppl 10)) K53- K61
PubMed
Rivera  ATyring  SK Therapy of cutaneous human papillomavirus infections. Dermatol Ther 2004;17 (6) 441- 448
PubMed
Albarran Y Carvajal  Ade la Garza  ACruz Quiroz  BJ  et al.  MVA E2 recombinant vaccine in the treatment of human papillomavirus infection in men presenting intraurethral flat condyloma: a phase I/II study. BioDrugs 2007;21 (1) 47- 59
PubMed
Ault  KA Human papillomavirus vaccines and the potential for cross-protection between related HPV types. Gynecol Oncol 2007;107 (2) ((suppl 1)) S31- S33
PubMed
Slupetzky  KGambhira  RCulp  TD  et al.  A papillomavirus-like particle (VLP) vaccine displaying HPV16L2 epitopes induce cross-neutralizing antibodies to HPV11. Vaccine 2007;25 (11) 2001- 2010
PubMed
Pinto  LAViscidi  RHarro  CD  et al.  Cellular immune responses to HPV-18,-31, and -53 in healthy volunteers immunized with recombinant HPV-16 L1 virus like particles. Virology 2006;353 (2) 451- 462
PubMed
Harper  DMFranco  ELWheeler  CM  et al. HPV Vaccine Study group, Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow up from randomised control trial. Lancet 2006;367 (9518) 1247- 1255
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Prevaccine dorsal aspect of both hands. The right hand shows warts on the thumb periungually and index finger over the proximal interphalangeal joint and periungually. The left hand shows warts on the left thumb and left index finger.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Eight months after commencing treatment with arm injections of a recombinant quadrivalent human papillomavirus vaccine, the hands were free of all the warts.

Graphic Jump Location

Tables

References

Villa  LLCosta  RLPetta  CA  et al.  High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer 2006;95 (11) 1459- 1466
PubMed
FUTURE II Study Group, Prophylactic efficacy of a quadrivalent human papillomavirus (HPV) vaccine in women with virological evidence of HPV infection. J Infect Dis 2007;196 (10) 1438- 1446
PubMed
Markowitz  LEDunne  EFSaraiya  M  et al. Advisory Committee on Immunization Practices (ACIP), Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007;56 (RR-2) 1- 24
PubMed
Schiller  JTCastellsagué  XVilla  LLHildesheim  A An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Vaccine 2008;26 ((suppl 10)) K53- K61
PubMed
Rivera  ATyring  SK Therapy of cutaneous human papillomavirus infections. Dermatol Ther 2004;17 (6) 441- 448
PubMed
Albarran Y Carvajal  Ade la Garza  ACruz Quiroz  BJ  et al.  MVA E2 recombinant vaccine in the treatment of human papillomavirus infection in men presenting intraurethral flat condyloma: a phase I/II study. BioDrugs 2007;21 (1) 47- 59
PubMed
Ault  KA Human papillomavirus vaccines and the potential for cross-protection between related HPV types. Gynecol Oncol 2007;107 (2) ((suppl 1)) S31- S33
PubMed
Slupetzky  KGambhira  RCulp  TD  et al.  A papillomavirus-like particle (VLP) vaccine displaying HPV16L2 epitopes induce cross-neutralizing antibodies to HPV11. Vaccine 2007;25 (11) 2001- 2010
PubMed
Pinto  LAViscidi  RHarro  CD  et al.  Cellular immune responses to HPV-18,-31, and -53 in healthy volunteers immunized with recombinant HPV-16 L1 virus like particles. Virology 2006;353 (2) 451- 462
PubMed
Harper  DMFranco  ELWheeler  CM  et al. HPV Vaccine Study group, Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow up from randomised control trial. Lancet 2006;367 (9518) 1247- 1255
PubMed

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics
PubMed Articles