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      Nonavalent human papillomavirus vaccination as a treatment for warts in an immunosuppressed adult

      case-report
      , MD a , , , MD b
      JAAD Case Reports
      Elsevier
      human papillomavirus, immunosuppressed, vaccine, wart, HPV, Human papillomavirus

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          Abstract

          Introduction Common cutaneous warts caused by human papillomavirus (HPV) strains 1, 2, and 4, can be challenging to treat. Immunosuppressed patients are especially vulnerable to this infection, and the warts may cause physical and psychologic distress. There are currently 3 commercially available vaccines in the United States that target HPV strains commonly associated with the development of anogenital warts, cervical dysplasia, and cervical, vulvar, vaginal, and anal cancers. We report a case of an immunosuppressed adult with eruptive cutaneous warts who responded well to treatment with the nonavalent HPV vaccine (targeted against HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58). 1 Case report A 77 year-old white man with a long-term history of immunosuppression presented with a 6-month history of pruritic and eruptive white papules on the trunk and extremities. His medical history was significant for ulcerative colitis treated with long-term 6-mercaptopurine, 75 mg daily, and mesalamine, up to 800 mg 3 times daily, and a history of occasional cutaneous warts, totaling less than 7 at any time at previous dermatologic visits in the preceding 5 years. His warts had been treated with liquid nitrogen and salicylic acid and occasionally shave removal. The patient had no risk factors for HIV. On examination recently, the patient had more than 70 inflamed thick, scaly white plaques ranging in size from 2 to 20 mm on the trunk and extremities clinically consistent with warts (Fig 1, A and B). Initial management included shave removal of 6 larger, more cumbersome lesions and freezing of more than 20 smaller areas with liquid nitrogen. Pathology findings for each sample were consistent with verruca. HPV typing was not performed because of cost. Fig 1 A and B, Lower legs at baseline highlighting many inflamed warts. At follow-up 2 weeks later, the patient complained of continuing to develop new itchy white bumps. Different alternative treatments were discussed including the possibility of administering the HPV vaccine, based on several case reports of successful treatment of recalcitrant cutaneous warts.2, 3, 4, 5 The patient elected to try the nonavalent HPV vaccine and it was given at baseline and 2 and 6 months later. No additional treatments were performed during the vaccine period. The patient noticed a decrease in his warts and his level of pruritus within the first 3 weeks. Photos were obtained with the patient's permission at baseline and 6 months. The number of cutaneous warts dramatically decreased from the time of the initial vaccine administration to the 6-month time point (Fig 2, A and B). The warts did not fully clear, but the number of warts decreased over time without a change in his immunosuppressive medications, down to a low of 3 warts 15 months after the initial vaccine dose. Fig 2 A and B, Lower legs 6 months after the HPV vaccine series was initiated (seen at his appointment for the third and final vaccine administration). Discussion Routine vaccination against HPV has been available in most industrialized countries since 2006. First available as bivalent and quadrivalent vaccines, the nonavalent vaccine has been available since 2015. 6 It is targeted against HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 and for those older than 15 years, the recommended dosing schedule is at zero, 2, and 6 months. 6 It has been shown to produce a robust immune response with seroconversion rates approaching 100%. 1 Studies on HPV vaccine administration in immunosuppressed populations are sparse, but a multicenter trial did show adequate immunogenic response to quadrivalent vaccine administration in immunosuppressed children regardless of age or cause of immunosuppression. 7 Recalcitrant common warts, especially in the immunosuppressed population, can prove to be difficult to treat. Although many therapeutic options for warts exist, there is no definitive cure. Several case reports have described the successful use of quadrivalent HPV vaccine in treating recalcitrant warts.2, 3, 4, 5 Within the body of literature surrounding HPV vaccines, there is some indication for a cross-protection effect against HPV strains other than those targeted by the individual vaccine administered.8, 9, 10 Although the HPV strains that cause common warts may be less genetically related to those implicated in cervical, vulvar, and anal cancer, the possibility of cross-over effects with vaccines has been postulated previously.2, 3, 4 Interestingly, one case series reported success in treating children less than 14 years old with the quadrivalent vaccine, but less improvement was noted in teenagers (3 of 6 patients cleared) and in adults (1 of 4 patients cleared), perhaps indicating a more robust response to the vaccine in children. 4 Our patient quickly experienced both a decrease in the number of warts and decreased irritation by the warts after the initial administration of the nonavalent HPV vaccine. His warts did not fully clear by 6 months, as has been reported when previously describing good responses to HPV vaccine.2, 3, 4, 5 This finding may indicate a cross-protection effect for certain but not all of his HPV strains. We did not perform HPV typing in this case because of patient cost; however, HPV status has been previously examined in a case report showing clearance of cutaneous warts negative for HPV 6, 11, 16, and 18 but positive for a general probe for HPV. 3 Warts can spontaneously regress, and we cannot be certain that the vaccine played a role in the clearance of our patient's warts or in the previously reported cases. However, our patient saw a dramatic improvement in quality of life after administration of this vaccine. HPV vaccine administration should be considered a potential treatment alternative for recalcitrant warts in the immunosuppressed population. More specifically, our case provides evidence that the nonavalent vaccine may help decrease the morbidity associated with recalcitrant warts in this population.

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          Most cited references8

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          The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in sexually active women aged 16-26 years.

          We evaluated the impact of a quadrivalent human papillomavirus (HPV) vaccine on infection and cervical disease related to 10 nonvaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) associated with >20% of cervical cancers. The population evaluated included HPV-naive women and women with preexisting HPV infection and/or HPV-related disease at enrollment. Phase 3 efficacy studies enrolled 17,622 women aged 16-26 years. Subjects underwent cervicovaginal sampling and Pap testing on day 1 and then at 6-12-month intervals for up to 4 years. HPV typing was performed on samples from enrollment and follow-up visits, including samples obtained for diagnosis or treatment of HPV-related disease. All subjects who received 1 dose and returned for follow-up were included. Vaccination reduced the rate of HPV-31/33/45/52/58 infection by 17.7% (95% confidence interval [CI], 5.1% to 28.7%) and of cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS) by 18.8% (95% CI, 7.4% to 28.9%). Vaccination also reduced the rate of HPV-31/58/59-related CIN1-3/AIS by 26.0% (95% CI, 6.7% to 41.4%), 28.1% (95% CI, 5.3% to 45.6%), and 37.6% (95% CI, 6.0% to 59.1%), respectively. Although a modest reduction in HPV-31/33/45/52/58-related CIN2 or worse was observed, the estimated reduction was not statistically significant. These cross-protection results complement the vaccine's prophylactic efficacy against disease associated with HPV-6, -11, -16, and -18. Long-term monitoring of vaccinated populations are needed to fully ascertain the population-based impact and public health significance of these findings. ClinicalTrials.gov identifiers: NCT00092521 , NCT00092534 , and NCT00092482.
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            Human papillomavirus vaccines and the potential for cross-protection between related HPV types.

            The majority of human papillomavirus (HPV) belong to the genus alpha-papillomavirus, which can be further subdivided into species and then strains. Approximately 200 strains of HPV have been identified, and the whole genomes of approximately 100 strains have been (discovered) and completely sequenced. Between 13 and 18 HPV strains have been characterized as conferring a high oncogenic risk, with 12 of these strains belonging to the HPV species 7 (HPV-18, -39, -45, -59, -68) and species 9 (HPV-16, -31, -33, -35, -52, -58, -67). While strains belonging to the same species are phylogenetically related, they may differ biologically. The available data on whether natural HPV infection infers cross protection against other related strains from the same species are equivocal. There are data to indicate that following HPV infection, there appears to be a reduced risk of contracting the same strain of HPV. However, there is also evidence to indicate that natural infection with HPV does not confer group-specific immune protection or general protection from reinfection with genital HPV mucosal types. Recent studies conducted with HPV vaccines show data on cross-protection against related HPV strains. In vitro experiments with serum from recipients of the quadrivalent HPV vaccine (HPV-6/8/16/18) show neutralization of HPV 45 pseudovirions. Cross-protection following vaccination of women (n=776) with three doses of bivalent HPV vaccine (HPV-16/18) demonstrated that, over a period of up to 4.5 years, long-term vaccine efficacy was observed for HPV-16 and -18, and vaccine efficacy was also observed against incident infection with HPV-31 and -45. These findings are supported by the results of a large study (n=18,644) in women aged 15 to 25 years vaccinated with the adjuvant bivalent HPV vaccine (HPV-16/18). Over a period of 6 months, cross-protection was observed against persistent infections with HPV-45, -31 and -52, and at 12 months, modest protection was demonstrated against persistent infections with 12 combined oncogenic HPV types.
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              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.

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                Author and article information

                Contributors
                Journal
                JAAD Case Rep
                JAAD Case Rep
                JAAD Case Reports
                Elsevier
                2352-5126
                26 July 2017
                July 2017
                26 July 2017
                : 3
                : 4
                : 367-369
                Affiliations
                [a ]Penn State Hershey Medical Group, State College, Pennsylvania
                [b ]Dermatology Associates of Highland Park, Highland Park, Illinois
                Author notes
                []Correspondence to: Sara B. Ferguson, MD, Penn State Hershey Medical Group Dermatology, 32 Colonnade Way, State College, PA 16803.Penn State Hershey Medical Group Dermatology32 Colonnade WayState CollegePA16803 sferguson1@ 123456pennstatehealth.psu.edu
                Article
                S2352-5126(17)30110-8
                10.1016/j.jdcr.2017.05.007
                5537385
                28795126
                a6f43860-041b-4b3a-9a0b-f7580d3aa9b7
                © 2017 by the American Academy of Dermatology, Inc. Published by Elsevier, Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
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                Case Report

                human papillomavirus,immunosuppressed,vaccine,wart,hpv, human papillomavirus

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