Human papillomavirus: burden of illness and treatment cost considerations.

The monetary and personal costs to society of human papillomavirus (HPV) infection are enormous. In order to make a comparison of different treatment methods we reviewed the entire literature on HPV treatment from January 1966 to December 2003 using MEDLINE, with particular reference to published meta-analyses, randomized controlled and comparative studies. Patient-applied therapies offer patients the possibility of convenient and, on the whole, pain-free treatment. Podofilox (podophyllotoxin) and salicylic acid for genital and extragenital warts, respectively, have the additional advantage of being the most cost-effective treatments and, on this basis, they are to be commended as appropriate first-line agents. The second-line treatment of choice for common warts is cryotherapy. For recalcitrant common warts possible options include inosine pranobex with cryotherapy or electrosurgery, imiquimod with paring and occlusion, intralesional bleomycin, or diphencyprone. Alternative first-line and second-line treatments for genital warts would be either some form of surgical removal or imiquimod. The first option may be the cheapest but this has to be balanced against a degree of post-operative morbidity. Limited data from comparative studies do not show any clear difference in efficacy between cryotherapy, trichloroacetic acid, scissor excision, electrosurgery, and laser surgery in the treatment of genital warts, and the cost effectiveness of these therapies is probably similar to that of imiquimod. Cryotherapy and trichloroacetic acid are relatively expensive and inconvenient for patients and should be reserved as third-line treatments with certain exceptions, such as cryotherapy for meatal warts. The duration of treatment is significantly related to the number of warts present, the area covered by the warts, and the length of time the warts have been present. For recalcitrant anogenital warts third-line treatment options that show promise include surgery in combination with imiquimod or cidofovir cream. For squamous intraepithelial lesions that cannot easily be excised or physically ablated current treatment options include imiquimod and fluorouracil cream. The latter is an inexpensive option but causes the greatest morbidity. It is hoped that cidofovir may be added to this list if it becomes commercially available, and that protective and therapeutic HPV vaccines will transform the management of HPV in the future.

Treatment options for anal intraepithelial neoplasia and evidence for their effectiveness.

There is a growing range of treatment options for anal intraepithelial neoplasia (AIN). In HIV-positive patients, sustained treatment is often required to achieve clearance. The treatments considered are topically applied fluorouracil, imiquimod, cidofovir and trichloroacetic acid, the potential treatments of topical lopinavir and photodynamic therapy with aminolevulenic acid, and the surgical methods of electrosurgery, infrared coagulation and laser. Destructive treatment methods, possibly including TCA, are more effective than self applied topical treatments. Combining or alternating different treatments should be considered.

A double-blind, randomized controlled trial of the use of imiquimod cream for the treatment of anal canal high-grade anal intraepithelial neoplasia in HIV-positive MSM on HAART, with long-term follow-up data including the use of open-label imiquimod.

OBJECTIVE: To determine whether imiquimod was more effective than placebo for the treatment of high-grade anal canal intraepithelial neoplasia (HG-ACIN). DESIGN: Double-blind, randomized placebo-controlled clinical trial. METHODS: Sixty-four HIV-positive patients were randomized to self-application of imiquimod cream or matched placebo into the anal canal three times a week for 4 months. Response was assessed by cytology, high-resolution anoscopy and biopsy 2 months after therapy. All patients who failed to resolve were offered treatment with open-label imiquimod for a further 4 months. RESULTS: Fifty-three patients completed the study, of which 28 patients were on active drug and 25 patients on placebo. In the imiquimod group, four patients resolved and eight patients downgraded to low-grade squamous intraepithelial lesion (LSIL) with a median follow-up of 33 months. In the placebo group, one patient resolved. Imiquimod was significantly associated with a positive outcome (P = 0.003). Only one patient discontinued owing to side effects. Twenty-one patients entered a second open-label phase of treatment. Five of these patients cleared their anal canal intraepithelial neoplasia (ACIN) and four patients downgraded to LSIL. The overall mean duration of follow-up was 36 months. During this extended follow-up period, 61% have exhibited sustained absence of high-grade squamous intraepithelial lesion (HSIL). CONCLUSION: This study demonstrates the effectiveness of imiquimod for the treatment of ACIN, and the benefit of prolonged or repeated treatments. This form of therapy is likely to be especially valuable for patients with widespread multifocal ACIN who are otherwise difficult to treat, and should be considered as an adjunct to ablative therapy.

Human papillomavirus and anal intraepithelial neoplasia.

PURPOSE OF REVIEW: A review of recent developments in the understanding of the natural history of anal squamous carcinoma arising from areas of high-grade anal intraepithelial neoplasia. RECENT FINDINGS: Anal intraepithelial neoplasia is a consequence of chronic human papillomavirus infection in the anal canal and appears to be driven by high viral loads of human papillomavirus. In men who have sex with men with multiple sexual partners prevalent human papillomavirus infection does not decline with age, in contrast to heterosexual patients. Anal intraepithelial neoplasia is equally prevalent in different age groups of men who have sex with men, but in other respects what is known of its natural history resembles that of cervical intraepithelial neoplasia. Low-grade lesions frequently resolve, but high-grade lesions are much more stable. HIV-positives who practise receptive anal intercourse are at highest risk of anal intraepithelial neoplasia. Screening is easy to perform using cytology; the limitations of anal cytology being similar to those of cervical cytology. Patients with any grade of cytological abnormality require further investigation, ideally with high-resolution anoscopy, every 6 months. Successful treatments for individual small to medium-sized high-grade lesions include trichloroacetic acid, infra-red coagulation and laser. In HIV-positive patients the development of new lesions elsewhere is very likely. Topical agents for multifocal disease include imiquimod and cidofovir. SUMMARY: There is a need for large prospective cohort studies in men who have sex with men and HIV-positive patients to further our understanding of this disease and to evaluate treatment strategies.