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Table of Contents
CORRESPONDENCE
Year : 2021  |  Volume : 39  |  Issue : 3  |  Page : 141-142

Recalcitrant giant genital wart treated with the combination of measles–mumps–rubella vaccine and human papillomavirus vaccine


Department of Dermatology, Taipei Medical University-Shuang Ho Hospital, New Taipei, Taiwan

Date of Submission04-Mar-2021
Date of Decision13-Jun-2021
Date of Acceptance17-Jun-2021
Date of Web Publication09-Aug-2021

Correspondence Address:
Dr. Donald Liu
Department of Dermatology, Taipei Medical University-Shuang Ho Hospital, No. 291, Zhongzheng Road, New Taipei 23561
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ds.ds_31_21

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How to cite this article:
Weng TY, Lee WR, Liu D. Recalcitrant giant genital wart treated with the combination of measles–mumps–rubella vaccine and human papillomavirus vaccine. Dermatol Sin 2021;39:141-2

How to cite this URL:
Weng TY, Lee WR, Liu D. Recalcitrant giant genital wart treated with the combination of measles–mumps–rubella vaccine and human papillomavirus vaccine. Dermatol Sin [serial online] 2021 [cited 2021 Nov 28];39:141-2. Available from: https://www.dermsinica.org/text.asp?2021/39/3/141/323520



Dear Editor,

Genital wart (GW) is one of the most frequently encountered sexually transmitted diseases. It is caused by human papillomavirus (HPV) and affects patients' quality of life.[1] Numerous therapeutic approaches, alone or in combination, have been employed to treat GW, each with its pros and cons.[2] Treatment of GWs is often lengthy and of variable efficacy; moreover, poor response with large chronic recalcitrant lesions is frequently observed.

Our patient is a 66-year-old woman with a known history of diabetes mellitus, hyperlipidemia, and hypertensive heart disease. She presented to our outpatient department complaining of relapsing GWs with ulcerations over the vulva after unsuccessful electrocauterization. Pathology finding of skin biopsy was compatible with condyloma acuminatum. HPV DNA test showed detection of HPV genotype 11, 16, and 68.

We initially prescribed her a combination of weekly cryotherapy and thrice-weekly 5% topical imiquimod; however, she could not tolerate the intense local inflammatory reaction. We then switched to alternating cryotherapy with weekly intralesional measles–mumps–rubella (MMR) vaccine injections for 6 weeks [Figure 1]a, but the response was unsatisfactory. Next, we initiated a three-dose schedule of nonavalent HPV vaccine (GARDASIL ® 9, Merck Sharp and Dohme Corp.) at 0, 1, and 6 months[3] along with weekly intralesional MMR vaccine. A 30-gauge insulin needle was used to deliver 0.2–0.3 mL of the MMR vaccine into the largest lesion(s) over the labia majora and posterior labial commissure, with three injections administered per session. Two weeks after the first dose of the HPV vaccine, partial regression of GWs was noted. A substantial improvement followed by complete clearance was observed at 9 and 12 weeks after the first nonavalent HPV vaccine [Figure 1]b and [Figure 1]c, after which intralesional MMR was halted. Follow-up at 6 months after vaccination completion showed no recurrence. Aside from pain at the site of intralesional injection, no discomfort was reported.
Figure 1: (a) Before human papillomavirus vaccination. (b) Nine weeks after the first dose of the nonavalent human papillomavirus vaccine, notable regression of the lesion is observable. (c) Twelve weeks after the first nonavalent human papillomavirus vaccination, complete clearance of the lesion is observed.

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Treatment of anogenital warts can be classified into (1) patient-applied chemical treatment (e.g., podofilox and imiquimod), (2) physician-applied chemical treatment (e.g., podophyllin resin and trichloroacetic acid), (3) physical ablation (e.g., surgery, electrosurgery, and cryotherapy), (4) intralesional injections (e.g., 5-fluorouracil, Candida antigen, and MMR vaccine), and (5) others (e.g., duct tape and cimetidine). However, destructive methods, such as electrocautery, surgical resection, and cryotherapy, may not be suitable for treating extensive lesions as they are prone to disfiguring and prolonged downtime. Topical imiquimod is an effective alternative;[4] however, the HPV-expressed oncoproteins E6 and E7 play a role in immune dysregulation mechanism and contribute to the immune escape of HPV clearance by immune cells.[5]

Intralesional immunotherapy using different antigens has a lower recurrence rate than destructive methods. Both treated and distant untreated warts can be eradicated through intralesional immunotherapy in immunocompetent patients. The exact mechanism of action remains unclear, but intralesional immunotherapy may induce a cellular immune reaction, with an increase in the ability of the body to recognize and eliminate HPV-infected cells.[6] Intralesional immunotherapy induces a powerful functional nonspecific inflammatory response with enhanced proliferation of peripheral blood mononuclear cells,[7] demonstrating promising efficacy of intralesional MMR in common and anogenital warts.[6] It is generally well tolerated. Common adverse effects include injection pain and flu-like symptoms that subside soon after injection.

The nonavalent HPV vaccine is effective in preventing HPV group virus infection and reducing the risk of subsequent GW development.[8] Taken together, a possible explanation of the unsatisfactory response of our patient after MMR vaccine injections may be attributable to a weakened immune system due to aging,[7] chronic hyperglycemia, diffuse extent of viral infection, and the absence of relevant HPV antibodies. The HPV vaccine was administered based on the premise that after the provocation of the immune response through repeated intralesional MMR, the ability of antigen presentation cells in targeting the disease-specific antigens within the nonavalent HPV vaccine will be enhanced, ensuring successful viral eradication. The nonavalent HPV vaccine covered the main HPV genotypes of our patient (11 and 16); the viral major capsid protein L1 could be precisely targeted under immune response provocation.

To the best of our knowledge, this is the first report of extensive recalcitrant GWs exhibiting resistance to intralesional MMR vaccine injection but being successfully treated when it was combined with three scheduled courses of the nonavalent HPV vaccine. Another case report indicated the regression of massive coalescing condyloma after one dose of nonavalent HPV vaccine; however, that patient had a lengthy remission period, leaving the causal relationship uncertain.[9] A large randomized controlled trial is warranted to standardize our treatment recommendations and verify the role of the nonavalent HPV vaccine in the treatment of GWs, especially inoperable or intractable lesions.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

Prof. Woan-Ruoh Lee, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.



 
  References Top

1.
Mortensen GL, Larsen HK. The quality of life of patients with genital warts: A qualitative study. BMC Public Health 2010;10:113.  Back to cited text no. 1
    
2.
Gilson R, Nugent D, Werner RN, Ballesteros J, Ross J. 2019 IUSTI-Europe guideline for the management of anogenital warts. J Eur Acad Dermatol Venereol 2020;34:1644-53.  Back to cited text no. 2
    
3.
World Health Organization. “Human papillomavirus vaccines: WHO position paper, May 2017–Recommendations.: Vaccine 2017;35:5753-5.  Back to cited text no. 3
    
4.
Jung JM, Jung CJ, Lee WJ, Won CH, Lee MW, Choi JH, et al. Topically applied treatments for external genital warts in nonimmunocompromised patients: A systematic review and network meta-analysis. Br J Dermatol 2020;183:24-36.  Back to cited text no. 4
    
5.
Westrich JA, Warren CJ, Pyeon D. Evasion of host immune defenses by human papillomavirus. Virus Res 2017;231:21-33.  Back to cited text no. 5
    
6.
Aldahan AS, Mlacker S, Shah VV, Kamath P, Alsaidan M, Samarkandy S, et al. Efficacy of intralesional immunotherapy for the treatment of warts: A review of the literature. Dermatol Ther 2016;29:197-207.  Back to cited text no. 6
    
7.
Horn TD, Johnson SM, Helm RM, Roberson PK. Intralesional immunotherapy of warts with mumps, Candida, and Trichophyton skin test antigens: A single-blinded, randomized, and controlled trial. Arch Dermatol 2005;141:589-94.  Back to cited text no. 7
    
8.
Joura EA, Giuliano AR, Iversen OE, Bouchard C, Mao C, Mehlsen J, et al. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med 2015;372:711-23.  Back to cited text no. 8
    
9.
Kazlouskaya M, Fiadorchanka N. Regression of giant condyloma acuminata after one dose of 9-valent human papillomavirus (HPV) vaccine. Int J Dermatol 2019;58:e245-7.  Back to cited text no. 9
    


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