Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6 L2E7 vaccine: infection of external anogenital warts with multiple HPV types and failure of therapeutic vaccination

Background.Cellular immunity is involved in spontaneous clearance of anogenital warts caused, most typically, by human papillomavirus (HPV) type 6 or 11, supporting the concept of therapeutic vaccination. A therapeutic vaccine composed of HPV‐6 L2E7 fusion protein and AS02A adjuvant was evaluated in conjunction with conventional therapies in subjects with anogenital warts. Methods.A total of 457 subjects with anogenital warts were screened, of which 320 with HPV‐6 and/or HPV‐11 infection were enrolled into 2 double‐blind, placebo‐controlled substudies. Three doses of vaccine or placebo were administered along with either ablative therapy or podophyllotoxin. Results.Although a positive trend toward clearance was seen in patients infected with only HPV‐6, in neither substudy did the vaccine significantly increase the efficacy of conventional therapies, despite induction of adequate immune responses. Extensive HPV typing by polymerase chain reaction demonstrated that a majority of screened subjects (73.7%) were infected with HPV‐6 and/or HPV‐11 and that a large proportion (40.1%) were infected with multiple HPV types. HPV types that put subjects at high risk of development of cervical cancer were detected in 39.8% of subjects. Conclusions.Infection with multiple HPV types, including high‐risk types, is common in anogenital wart disease. Therapeutic vaccination failed to increase the efficacy of conventional therapies

Randomised controlled trial and economic evaluation of podophyllotoxin solution, podophyllotoxin cream, and podophyllin in the treatment of genital warts

Objectives: To evaluate the efficacy and cost effectiveness of self applied podophyllotoxin 0.5% solution and podophyllotoxin 0.15% cream, compared to clinic applied 25% podophyllin in the treatment of genital warts over 4 weeks. Methods: We conducted a randomised controlled trial in 358 immunocompetent men and women with genital warts of 3 months’ duration or less. Results: In the principal analysis both podophyllotoxin solution (OR 2.93, 95% CI 1.56 to 5.50) and podophyllotoxin cream (OR 1.97, 95% CI 1.04 to 3.70) were associated with significantly increased odds of remission of all warts compared to podophyllin. We performed two further analyses. When subjects defaulting from follow up were assumed to have been cured odds of remission of all warts were also significantly increased both for podophyllotoxin solution (OR 3.04, 95% CI 1.68 to 5.49) and for podophyllotoxin cream (OR 2.46, 95% CI 1.38 to 4.40). When subjects defaulting from follow up were assumed not to have been cured odds of remission of all warts were significantly increased for podophyllotoxin solution (OR 1.92, 95% CI 1.13 to 3.27), but not for podophyllotoxin cream (OR 1.17, 95% CI 0.69 to 2.00). Local side effects were seen in 24% of subjects, and recurrence of warts within 12 weeks of study entry in 43% of all initially cleared subjects, without statistically significant differences between the treatment groups. Direct, indirect, and total costs were similar across the three treatment groups. Podophyllotoxin solution was the most cost effective treatment, followed by podophyllotoxin cream, with podophyllin treatment being the least cost effective. Conclusions: Self treatment of anogenital warts with podophyllotoxin showed greater efficacy and cost effectiveness than clinic based treatment with podophyllin