Resolution of Novel Human Papillomavirus–induced Warts after HPV Vaccination

Steffi Silling

, Ulrike Wieland, Marko Werner, Herbert Pfister, Anja Potthoff, and Alexander Kreuter

Author affiliations: University of Cologne, Cologne, Germany (S. Silling, U. Wieland, M. Werner, H. Pfister); Ruhr University, Bochum, Germany (A. Potthoff, A. Kreuter); Helios St. Elisabeth Hospital, Oberhausen, Germany (A. Kreuter)

Abstract

Human papillomavirus (HPV) XS2 was isolated from warts on an immunosuppressed patient. After HPV vaccination, the warts resolved. HPVXS2 was also found in warts and normal skin of HIV-positive patients and rarely in HIV-negative controls. Further studies should elucidate the mechanisms that lead to wart clearance.

Human papillomaviruses (HPVs), small, double-stranded DNA viruses with a circular genome of ≈8,000 bp, are assigned to different genera and species on the basis of their major capsid protein gene (L1) nucleotide sequence, which reflects their tropism (cutaneous or mucosal) and potential to induce tumors. Most HPVs belong to genera alpha (e.g., genital and wart-associated types), beta, or gamma (cutaneous types) (1). HPV infections are common, and the prevalence of cutaneous viral warts is 3%–5% in children (2). Warts, benign HPV-induced lesions, usually regress spontaneously within several months. Immunodeficiency predisposes to persistent HPV infections and the development of generalized verrucosis (2,3).

We report the remission of cutaneous warts of prolonged duration in an immunosuppressed patient after HPV vaccination. The study was performed according to the declaration of Helsinki; written informed consent was obtained from the patient.

The Patient

In 1979, a 41-year-old, White woman received a diagnosis of B cell chronic lymphocytic leukemia and was treated with chlorambucil and prednisolone, followed by radiation therapy and splenectomy, resulting in a durable, complete remission of the leukemia. In October 2002, breast cancer was detected in the patient; the breast was surgically removed, and lymph node dissection was performed. Six cycles of chemotherapy were administered during November 2002–March 2003. In February 2010, after a 12-year history of slowly progressing cutaneous warts, the patient sought medical care for numerous, flat, erythematous warts that were coalescing into large plaques on her forearms, backs of hands, and fingers (Technical Appendix

[PDF - 50 KB - 1 page] Figure). Immunophenotyping revealed a markedly decreased CD4/CD8 ratio (Table). During October 2005–December 2009, the patient received topical and ablative treatments for the warts (salicylic acid, podophyllotoxin, 5-fluoruracil cream, imiquimod 5% cream, cryosurgery, surgical curettage, electrocautery, and CO₂ laser therapy), but clinical improvement was not sustained.

Complete regression of cutaneous warts has been reported in persons after HPV vaccination (4,5); thus, we vaccinated the patient with the quadrivalent HPV (qHPV) vaccine (Gardasil, Sanofi Pasteur MSD SNC, Lyon, France), which contains L1 proteins of HPV types 6, 11, 16, and 18 as virus-like particles. Three doses were given during July 2010–January 2011. The patient’s pre- and postvaccination CD4/CD8 counts did not differ substantially (Table). In April 2011, three months after the third injection, all skin lesions had resolved (Technical Appendix

[PDF - 50 KB - 1 page]Figure, panel B), and in July 2011 and March 2012, the patient was still in complete remission.