Precedence for Locoregional Therapies to treat Cervical Dysplasia
It is well established that cervical cancer is caused by persistent infection with one or more of the oncogenic human papilloma virus (HPV) genotypes for a period longer than 2 years 42,43. HPV infection is common worldwide, with a lifetime cumulative risk of greater than 80% 44. To date only a few drug-based locoregional therapies have been developed for HPV infection which are approved for use in clinical practice, however, none of them are licensed for the management of cervical dysplasia. These therapies target either the molecular virology of HPV infection, the neoplasia itself, or the immune response to the virus (or indeed all three modalities) leading to viral clearance or lesion elimination45. Strategies that target the HPV virus aim to reduce the rate of recurrence by focusing on the cause of the lesions and thereby have an impact on the amount of latent and subclinical HPV DNA rather than just removing the neoplasia 45. There is precedence in the literature for locoregional therapies to treat cervical dysplasia either indirectly by targeting the HPV infection or directly by treating the cancer. Details of treatments so far trialed have been reviewed extensively elsewhere 46. Briefly, topical therapies studied so far have included immune modulators such as imiquimod 47–49, antiproliferative therapies such as 5Fluorouracil (5-FU) 50,51, antivirals such as Cidofovir 52, Lopinavir and Ritonavir, a combination oral HIV protease inhibitor (Lopimune) 53–55, Vidarabine 56,57 and Terameprocol57,58 and hormonal drugs for treatment of CIN 1 such as Dehydroepiandrosterone (DHEA) 59. In addition, other approaches include herbal/non-pharmacologic therapies such as green tea 60, praneem, the seed extract ofAzadirachta indica 61, glycyrrhizinic acid62 and curcuma (turmeric). Of all these, the randomized trials of Imiquimod, 5-FU, and Cidofovir have had the most promising results 46. These will be discussed in more detail in the ensuing review.