Chapter 17: Genital human papillomavirus infections--current and prospective therapies.

Many therapies are available for the treatment of human papillomavirus (HPV)-associated disease, particularly external genital warts. However, at present, these therapies aim to remove the lesion rather than specifically target HPV infection. When disease and infection are local, as in cervical intraepithelial neoplasia (CIN), excisional therapies removing lesion and transformation-susceptible cells are highly effective. However, when infection is regional, as is usually the case for the anogenital warts, vulval intraepithelial neoplasia (VIN), anal intraepithelial neoplasia (AIN), penile intraepithelial neoplasia, and vaginal intraepithelial neoplasia, then current treatments are generally inadequate, with high recurrence rates. Future therapies will be directly or indirectly antiviral, targeting HPV protein functions or enhancing the ability of the immune system to resolve infection or inducing apoptosis indirectly in HPV-infected cells. In the short to the medium term, immunotherapies for low-grade disease are the most likely to be in the clinic. Vaccines targeting the E1 and E2 early proteins combined with immunomodulators or conventional adjuvants that induce a strong cell-mediated HPV antigen-specific response and good immune memory would be the predicted combination. Vaccines designed to target high-grade intraepithelial disease, even when used in combination with immunomodulators, are unlikely to effect lesion clearance in more than a fraction of the cases. However, they may have a role as adjunct therapy after cervical conization to prevent the recurrence of CIN or HPV reinfection. They certainly appear to have a role in multifocal disease, such as VIN and AIN, where partial clearance may be effected and lesion size reduced enough for effective ablative or excisional therapy. It seems unlikely that anti-HPV chemotherapies specifically targeting HPV protein functions will be in the clinic in the medium term. However, agents such as indole-3-carbinol have shown efficacy in small clinical trials, and if these effects are confirmed in larger, randomized, placebo-controlled trials, they could be clinically useful.