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.