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Review
. 2012 Nov 20;30 Suppl 5(0 5):F71-82.
doi: 10.1016/j.vaccine.2012.05.091.

"V体育ios版" Therapy of human papillomavirus-related disease

Affiliations
Review

Therapy of human papillomavirus-related disease

Peter L Stern et al. Vaccine. .

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 HPV-associated 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 VSports手机版. 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 anti-apoptotic 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. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. .

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V体育ios版 - Conflict of interest statement

INH: no conflicts of interest.

Figures

Figure 1
Figure 1
Natural immune control of HPV infection. APC: Antigen-presenting cell. Taken with permission from: The Immunobiology of Human Papillomavirus Associated Oncogenesis; Stern PL, Einstein MH. In: HPV and Cervical Cancer: Achievements in Prevention and Future Prospects. Borrutto F, De Ridder M, editors. Dordrecht: Springer Science+Business Media B.V; 2012. See also Box 1.
Figure 2
Figure 2
Loss of immune control and escape in HPV-associated neoplasia. APC: Antigen-presenting cell; CTL: Cytotoxic T lymphocyte; HLA: Human leukocyte antigen; IFN: Interferon; IL-10: Interleukin 10; T reg: Regulatory T cell; TGF: Transforming growth factor. Taken with permission from: The Immunobiology of Human Papillomavirus Associated Oncogenesis; Stern PL, Einstein MH. In: HPV and Cervical Cancer: Achievements in Prevention and Future Prospects. Borrutto F, De Ridder M, editors. Dordrecht: Springer Science+Business Media B.V; 2012. See also Box 2.
Figure 3
Figure 3
Key HPV E6/E7 functions to control cell proliferation and survival. Strategies for drug targeting of HPV oncoproteins are shown. See also Box 3.

References

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