Related Experiment Videos
Chapter 17: Genital human papillomavirus infections--current and prospective therapies
1Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1Q0, UK. mas@mole.bio.cam.ac.uk
Abstract:
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.
Insights
Current human papillomavirus (HPV) treatments remove lesions but don't target the infection. Future therapies may include immunotherapies and antiviral agents to combat HPV disease and prevent recurrence.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Current treatments for human papillomavirus (HPV)-associated diseases, like external genital warts, focus on lesion removal rather than targeting the underlying viral infection.
- While excisional therapies are effective for localized cervical intraepithelial neoplasia (CIN), regional infections (e.g., VIN, AIN) often have high recurrence rates with existing treatments.
Purpose of the Study:
- To review current therapeutic limitations for HPV-associated diseases and explore potential future antiviral and immunotherapeutic strategies.
- To assess the likely timeline and efficacy of emerging treatments, including vaccines and chemotherapeutic agents.
Main Methods:
- Literature review of existing and proposed therapies for HPV-associated diseases.
- Analysis of the potential mechanisms of action for future treatments, including direct antiviral targeting and immune system enhancement.
- Evaluation of the predicted clinical utility of immunotherapies and chemotherapies for various grades and locations of HPV disease.
Main Results:
- Future therapies are expected to be directly or indirectly antiviral, targeting HPV proteins or boosting the immune response.
- Immunotherapies, particularly vaccines targeting E1/E2 proteins with immunomodulators, are anticipated for short-to-medium term clinical use, especially for low-grade disease and adjunct therapy.
- While vaccines may not fully clear high-grade lesions, they could aid in preventing CIN recurrence and managing multifocal VIN/AIN.
- Anti-HPV chemotherapies targeting viral protein functions are less likely in the medium term, though agents like indole-3-carbinol show promise in early trials.
Conclusions:
- Short-to-medium term advancements in HPV treatment will likely involve immunotherapies for low-grade lesions and as adjuncts to prevent recurrence.
- Vaccine-based strategies hold potential for managing multifocal VIN and AIN by reducing lesion size for subsequent therapies.
- Further research and large-scale trials are needed to validate the efficacy of agents like indole-3-carbinol for clinical application against HPV infections.