Utility of the Human Papillomavirus Vaccination in Management of HPV-associated Cutaneous Lesions

Jane Gay, BA; Nathan Johnson, MD; Varun Kavuru, BA; Mariana Phillips, MD


Skin Therapy Letter. 2021;26(2):6-8. 

In This Article

Abstract and Introduction


Human papillomavirus (HPV)-induced cutaneous disease is a common complaint for patients presenting for dermatology evaluation. Infection by HPV is the major etiologic factor in the development of cutaneous warts, epidermodysplasia verruciformis, and possibly a subset of cutaneous squamous cell carcinoma. Carcinoma of the genitourinary tract, most notably cervical carcinoma, is the most severe manifestation of infection with specific serotypes of HPV. For this reason, the HPV immunization (Gardasil) was developed in 2006 and upgraded in 2018 to a nonavalent formulation that includes serotypes 6, 11, 16, 18, 31, 33, 45, 52, 58. While immunization is highly effective at preventing infection with serotypes included in the formulation, it is less clear if the immunization can aid in managing active HPV infection. This review examines the available literature regarding the role of HPV immunization in managing common warts, genital warts, keratinocyte carcinoma, and epidermodysplasia verruciformis.


Human papilloma virus (HPV) is a non-enveloped, double-stranded circular DNA virus. Transmission usually occurs through skin-to-skin contact, but the virus can also be transmitted vertically and via fomites, such as transvaginal ultrasounds and colposcopes.[1] Over 100 HPV strains exist. HPV types 1, 2, 4, 7, 27, 57, and 65 frequently cause common, plantar, and flat warts,[2] while types 6 and 11 are the usual agents behind genital warts and recurrent respiratory papillomatosis.[3,4] The high-risk HPV types, 16 and 18, are responsible for the majority of HPV-induced carcinomas of the cervix, vagina, vulva, anus, rectum, penis, and oropharynx, with a minority caused by the less prevalent high-risk types (31, 33, 35, 45, 52, 58).[4–6] Other dermatologic conditions associated with HPV infection include keratinocyte carcinomas of the skin[7,8] and epidermodysplasia verruciformis (EV), which is caused by mutations that increase susceptibility to β-genus HPV strains.[9]

The first formulation of the HPV vaccine (quadrivalent Gardasil®), US FDA approved in 2006, covered types 6, 11, 16, and 18. The vaccine was designed mainly to aid in the prevention of cervical carcinomas, as reflected in its initial target population of female patients aged 9–26 years. Like other non-living vaccines, the immunization employed an adjuvant (aluminum hydroxide, 225 mg) that served to amplify the immune response. In 2009, a bivalent formulation (Cervarix®) that covered just serotypes 16 and 18 was approved by the FDA. Cervarix contains a proprietary adjuvant (3-O-desacyl-4 monophosphoryl lipid A [AS04]) that has increased potencycompared to aluminum hydroxide.[10] Also in 2009, FDA approval was extended to include males between 9–26 years of age. Most recently, Gardasil upgraded to a nonavalent formulation that includes 9 serotypes (6, 11, 16, 18, 31, 33, 45, 52, 58) as well as an increase in adjuvant dose to 500 mg of aluminum hydroxide.[11] Additionally, approved coverage was expanded by the FDA in 2018 to include all individuals (from 9 years of age), male and female, up to 45 years old.

The effectiveness of HPV immunization in preventing HPV infection in naive individuals and subsequent cervical dysplasia and carcinoma is excellent and well-documented.[5,12] An interesting question that has arisen since widespread acceptance of the HPV immunization is what role does immunization play, if any, in the management of active HPV infection. Anecdotal reports and case series have described improvement or resolution of common and genital warts with administration of HPV vaccination, but conflicting reports documenting little to no benefit have also been published. This article provides a brief review of the literature exploring the potential utility of the HPV immunization in treating HPV-related dermatologic conditions.