Therapy of human papillomavirus-related disease

Peter L. Stern, Sjoerd H. van der Burg, Ian N. Hampson, Thomas R. Broker, Alison Fiander, Charles J. Lacey, Henry C. Kitchener, Mark H. Einstein

Research output: Contribution to journalReview article

93 Scopus citations

Abstract

This chapter reviews the current treatment of chronic and neoplastic human papillomavirus (HPV)-associated conditions and the development of novel therapeutic approaches. Surgical excision of HPVassociated lower genital tract neoplasia is very successful but largely depends on secondary prevention programmes for identification of disease. Only high-risk HPV-driven chronic, pre-neoplastic lesions and some very early cancers cannot be successfully treated by surgical procedures alone. Chemoradiation therapy of cervical cancer contributes to the 66-79% cervical cancer survival at 5 years. Outlook for those patients with persistent or recurrent cervical cancer following treatment is very poor. Topical agents such as imiquimod (immune response modifier), cidofovir (inhibition of viral replication; induction apoptosis) or photodynamic therapy (direct damage of tumour and augmentation of anti-tumour immunity) have all shown some useful efficacy (~50-60%) in treatment of high grade vulvar intraepithelial neoplasia (VIN). Provider administered treatments of genital warts include cryotherapy, trichloracetic acid, or surgical removal which has the highest primary clearance rate. Patient applied therapies include podophyllotoxin and imiquimod. Recurrence after "successful" treatment is 30-40%. Further improvements could derive from a rational combination of current therapy with new drugs targeting molecular pathways mediated by HPV in cancer. Small molecule inhibitors targeting the DNA binding activities of HPV E1/E2 or the antiapoptotic consequences of E6/E7 oncogenes are in preclinical development. Proteasome and histone deacetylase inhibitors, which can enhance apoptosis in HPV positive tumour cells, are being tested in early clinical trials. Chronic high-risk HPV infection/neoplasia is characterised by systemic and/or local immune suppressive regulatory or escape factors. Recently two E6/E7 vaccines have shown some clinical efficacy in high grade VIN patients and this correlated with strong and broad systemic HPV-specific T cell response and modulation of key local immune factors. Treatments that can shift the balance of immune effectors locally in combination with vaccination are now being tested.

Original languageEnglish (US)
Pages (from-to)F71-F82
JournalVaccine
Volume30
Issue numberSUPPL.5
DOIs
StatePublished - Jan 1 2012

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Keywords

  • HPV drug targets
  • HPV-related disease therapy
  • Therapeutic HPV vaccines

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Stern, P. L., van der Burg, S. H., Hampson, I. N., Broker, T. R., Fiander, A., Lacey, C. J., Kitchener, H. C., & Einstein, M. H. (2012). Therapy of human papillomavirus-related disease. Vaccine, 30(SUPPL.5), F71-F82. https://doi.org/10.1016/j.vaccine.2012.05.091