Human Papilloma Virus Genotypes and Treatment Outcomes of Intralesional Immunotherapy of Anogenital Warts

Human papillomavirus (HPV), a member of the Papillomaviridae family, is a small, icosahedral, non-enveloped virus with a circular double-stranded DNA genome. Sexually transmitted HPV, which mainly infects mucosal and keratinized epithelium, has a cytopathic effect on the epithelium. Genital mucosal HPV infection is persistent and multifocal and can be subclinical (Alacam \& Bakir, 2021). Infection with HPV causes a large proportion of cervical, vaginal, vulvar, anal, and penile cancers, as well as genital warts (Choi, 2019).

Anogenital warts are common benign dermatological conditions caused by different HPV genotypes, with serotypes 6, 11, 16, and 18 being the most causative types (Santos-López et al., 2015). Their prevalence varies according to geographical locations. Data is not yet available on the HPV burden in the general population of Egypt (Elazab et al., 2021). In October 2014, a very important multicenter observational study in Egypt concluded that the prevalence of HPV among Egyptian women aged 18 years or more is about 10.4%, with the highest prevalence of HPV infection being observed among women aged 45-54 years (Shaltout et al., 2014).

Different modalities are available for the treatment of warts, such as topical podophyllin, imiquimod, podophyllotoxin, or trichloroacetic acid, surgical excision, electrosurgery, cryosurgery, laser surgery, and intralesional immunotherapy (Gill, 2021; Nofal et al., 2022). Available treatments are time-consuming, painful, and can leave scars or hypopigmentation. Furthermore, recurrence rates after any treatment range from 6% to 100% (Ciccarese et al., 2019). As a result, there has been a demand for safer modalities to treat recalcitrant warts. Immunotherapy presents an alternative approach to the management of warts as it provides ease of application, but even distant lesions get resolved with application to a single lesion. Immunotherapy has been performed with imiquimod, BCG vaccine, HPV vaccines, and auto implantation therapy (Gill, 2021).

Three HPV vaccines are licensed as protective measures against the development of genital warts, cervical cancer, and other anogenital cancers. They include the bivalent vaccine targeting serotypes 16/18 (Cervarix), the quadrivalent vaccine targeting serotypes 6/11/16/18 (Gardasil), and the nonavalent vaccine targeting serotypes 6/11/16/18/31/33/45/52/58 (Gardasil-9) (Vaccine Information Statement | HPV | VIS | CDC, 2021). There is a strong immune response against the HPV vaccine that not only causes the clearance of local wart lesions but also causes the clearance of distant lesions. The vaccine is designed to elicit neutralizing antibody responses which prevent initial infection with HPV, but in warts it mainly acts by mounting cell-mediated and humoral responses which help in the clearance of warts. The quadrivalent HPV vaccine contains inactive L1 proteins from four different strains: 6, 11, 16, and 18; synthesized in the yeast Saccharomyces cerevisiae (Gill, 2021).