Human Papilloma Virus Research - Therapy

Lacey CJ. Hull York Medical School, University of York, Heslington, York YO10 5DD, UK. charles.lacey@hyms.ac.uk

Genital human papillomavirus (HPV) infection is very common, and often sub-clinical and usually resolves without any treatment. Genital warts are caused by HPV 6/11 infection and are one of the commonest clinically recognised disease manifestations of genital HPV. Subjects with genital warts usually perceive them as cosmetically disfiguring, often leading to adverse psychological symptoms, and most subjects with genital warts will present requesting treatment. A wide variety of treatments are available including both provider- and patient-applied therapies. Various individual subject and disease factors mediate appropriate therapy choice. Some of the treatments that are used for genital warts can also be used for some cases of intraepithelial neoplasia caused by high-oncogenic risk HPVs occurring at vulval, anal or penile sites. Specific treatment considerations apply to genital warts in pregnancy and laryngeal papillomatosis and these are also discussed.

Dev Biol (Basel). 2004;116:193-200; discussion 229-36.

CoVal fusions: a therapeutic vaccine platform using heat shock proteins to treat chronic viral infection and cancer.

Neefe JR, Chu NR, Mizzen L. Stressgen Biotechnologies, Collegeville, PA, USA. jneefe@stressgen.com

We have developed an immunization platform which combines heat shock proteins (Hsp) with protein antigens, such as viral or cancer targets, into a single recombinant fusion protein. Pre-clinical data demonstrate the ability of Hsp fusion proteins to induce antigen-specific cytotoxic T lymphocytes, Type 1 cytokines and anti-tumour immunity. One Hsp fusion protein, HspE7, is now in clinical development for therapy of diseases caused by human papillomavirus (HPV). HPV infection is associated with development of proliferative lesions (papillomas or warts) as well as malignant lesions (anogenital dysplasia and cancer). HspE7 has been shown in efficacy trials to be active against genital warts and anal dysplasia, and a trial is underway in another HPV indication, recurrent respiratory papillomatosis. Having observed therapeutic activity for our lead product HspE7 in humans, we are currently developing Hsp fusion proteins as therapeutic vaccines for other chronic viral infections. Potential targets include hepatitis B, herpes simplex, hepatitis C, and human immunodeficiency virus.

Clin Dermatol. 2004 Nov-Dec;22(6):481-6.

Genital warts.

Dupin N. Service de Dermato-Venereologie, Pavillon Tarnier, Hopital Cochin, Universite Rene Descartes, Paris, France. nicolas.dupin@cch.ap-hop-paris.fr

Genital warts are an epidermal manifestation attributed to the epidermotropic human papillomavirus (HPV). Over 100 types of double-stranded HPV have been isolated and completely sequenced thus far. HPV are grouped into low-risk (non-oncogenic) types such as type 6 and type 11, which cause benign anogenital warts (condyloma accuminata), and high-risk (oncogenic) types, such as types 16, 18, 31, and 45, which occasionally lead to cancer.

Publication Types:
• Review

Skin Pharmacol Physiol. 2004 Sep-Oct;17(5):258-66.

Molecular analysis of the effect of topical imiquimod treatment of HPV 2/27/57-induced common warts.

Jacobs S, Grussendorf-Conen EI, Rosener I, Rubben A. Department of Dermatology, University Hospital of the RWTH Aachen, Aachen, Germany.

Imiquimod is effective in the treatment of genital warts and clinical studies suggest activity against common warts as well. We have analyzed the effect of topical imiquimod on gene expression and virus load in human papilloma virus (HPV) 2/27/57-induced common warts. mRNA was extracted from keratinocyte culture, from normal skin, from three untreated common warts and from three common warts treated topically with 5% imiquimod cream twice daily. Differential gene expression was demonstrated by RT-PCR and by cDNA microarray hybridization. We further analyzed viral DNA content in scales from three superficially pared imiquimod-treated warts by real-time PCR. Comparison of normal skin with wart tissue revealed that HPV 2/27/57 infection led to an induction of IL-6, IL-10 and interferon-gamma inducible protein (IP10) and to an up-regulation of TGF-beta. We could further detect expression of PCTAIRE-3, WNT2B, frizzled-3, notch-2, notch-4 and BRCA2 in normal skin and common warts. Analysis of imiquimod-treated warts demonstrated that imiquimod enhanced IL-6 expression and induced IL-8, GM-CSF, MRP-8 and MRP-14. It could also be shown that imiquimod led to an infiltration of wart tissue with macrophages and to a strong decrease of viral copy number in warts within 3 months of treatment. Our data thus provide molecular proof of principle for imiquimod treatment of cutaneous common warts. 2004 S. Karger AG, Basel

Gynecol Oncol. 2004 Sep;94(3):803-10.

Comparative analysis of characteristics of women with cervical cancer in high- versus low-incidence regions.

Liu J, Rose B, Huang X, Liao G, Carter J, Wu X, Thompson C. Department of Infectious Diseases and Immunology, University of Sydney, Sydney, Australia.

OBJECTIVE: To identify particular characteristics that might help explain the markedly higher rate of invasive cervical cancer in southern China as compared with Australia. METHODS: One hundred eighty-five women with cervical cancer were recruited between 1999 and 2001: 106 from Guangzhou and Changsha (southern China), and 79 from Sydney (southeast Australia). Demographic and risk factor information was obtained by questionnaire; clinicopathologic data were extracted from hospital records. The human papillomavirus (HPV) status of cancer biopsies was ascertained by consensus PCR assays, direct sequencing and/or Amplicor trade mark hybridisation. RESULTS: The mean age of the Chinese was significantly lower than the Australians (44 versus 53 years), although mean age at first sexual intercourse was similar. Australian women were more likely to smoke, to report multiple sexual partners and to have a history of sexually transmitted diseases (but not of genital warts). However, they were better educated, were more frequent users of barrier contraception and were far more likely to report regular Pap smears before diagnosis. The HPV positivity rate of Chinese cancers (83%) was less than Australian tumours (90%); but HPV 16 and 18 were the most common genotypes in both populations (59% and 77%), and predominated in cancers from younger women. HPV types 58 or 59 were amplified from 12 (14%) of the Chinese but from only one Australian cancer. CONCLUSIONS: Cervical cancer is not only more common in China but also develops at a younger age than in Australia. While significant differences in some risk factors were observed, the much lower participation in cervical screening in southern China is likely to be of greatest consequence.

Eur J Gynaecol Oncol. 2004;25(4):475-7.

A second Pap smear during colposcopy: is it really worth it?

Kourounis GS, Michail GD, Ravazoula P. Patras University, Greece.

The aim of this study was to determine whether the clinical value of a second Pap smear during colposcopy outweighed its cost-effectiveness and reliability parameters. We studied retrospectively 569 cases focusing on A) The initial Pap smear, B) The smear performed during colposcopy, C) The colposcopic findings, and D) The histopathological reports of the cases where biopsy sampling was performed. In 380 patients (67%), the second Pap smear corresponded to the first one. In 13% of the patients, the cytological lesions were worse (particularly in 2% of the patients staging increased from HPV-associated reactive cellular changes to CIN II, or from CIN I to CIN III), and in 20% slighter than the initial. In 79% of the cases revealing more serious lesions in the second smear, the histological result of the biopsy corresponded to that of the initial smear. Conclusively, only 2% seem to benefit from a second repeat Pap smear during referral colposcopy.

Human Papilloma Virus Research - Therapy for HPV Links

How to Prevent and treat HPV - Describes what the latest research has to say about the prevention and treatment of HPV, dysplasia, and cervical cancer.

Research on Diagnostics and Treatments for Cervical Cancer - Explains the importance of participating in cervical cancer clinical trials and how even participants who take placebos contribute and benefit from volunteering.