It is estimated that 10-30% of the adult population in Canada is infected with human papilloma virus (HPV). While high-risk strains of HPV cause various types of cancer, low-risk strains can cause condyloma acuminate, also known as external anogenital warts (EGWs). EGWs are highly contagious and are, therefore, one of the most common forms of sexually transmitted infections.
The prevalence of EGWs in Canada is an estimated 1.8%, with an annual incidence rate of 154/100,000 for males and 120/100,000 for females. Patients with EGWs present with one or several cauliflower-like growths on the genitals and/or anal regions and clinical appearance is often sufficient for a diagnosis. EGWs are associated with a significant burden of illness and considerable impairment of patients’ emotional and sexual well-being. Although up to 50% of untreated cases spontaneously regress at 6 months, it is impossible to predict which lesions will regress, remain unchanged, or proliferate; therefore it is recommended that treatment be offered to all patients with EGWs.
EGW treatment includes provider-assisted and patient-applied therapies or a combination of these modalities. Treatment can be categorised as ablative, anti-proliferative, or immunomodulatory. CO2 laser, trichloroacetic acid, excision, cryotherapy, and electrocautery are ablative therapies that necessitate the assistance of a trained healthcare professional. Until recently, patient-applied therapies were either anti-proliferative or immunomodulatory in nature.
Podophyllin 10-25% and podophyllotoxin 0.5% are patient-applied anti-proliferative agents, while imiquimod is an immunomodulatory agent that is available in both 5% and 3.75% formulations. Podophyllotoxin and imiquimod are considered the first choice among patient-applied treatment options; however, despite the greater ease and autonomy offered by patient-applied therapy, clearance rates with these treatments are lower than those achieved with physician-assisted options. Furthermore, lesion reappearance is common regardless of treatment choice as there is no way to eradicate the underlying viral infection.
Sinecatechins ointment 10%, a new patient-applied treatment formulated from green tea (Camellia sinensis) extracts, has recently been licensed in Canada for the treatment of EGWs. Sinecatechins 10% ointment is comprised of >85% catechins, which are flavonoids responsible for the antioxidant effects of green tea. Sinecatechins 10% ointment contains eight different catechins, of which >55% is epigallocatechin-3-gallate (EGCG), the most abundant and potent catechins. Although the exact mechanisms of action of sinecatechins 10% ointment in regression of EGWs are currently unknown, they are likely multimodal, consisting of antiviral, pro-apoptotic and anti-inflammatory responses.
The antiviral properties of EGCG may result from the inhibition of activator protein 1 (AP-1) transcriptional activity that effectively down-regulate expression of HPV genes. Transcription of anti-apoptotic HPV genes by the infected cell could be counteracted by EGCG directly activating pro-apoptotic proteins as well as up-regulating and down-regulating the expression of pro- and anti-apoptotic proteins, respectively, resulting in cell death.
EGCG also possesses anti-inflammatory activity by inducing anti-inflammatory interleukin (IL)-12 and reducing pro-inflammatory IL-10 activity. This would shift towards a T helper cell type 1 (Th1)-mediated immune response promoting the elimination of HPV-infected cells by the immune system. The various catechins and other molecular constituents of sinecatechins ointment likely work synergistically to modulate these complex biologic pathways to promote the regression of EGWs.
Therefore, although the exact mechanisms of action of sinecatchins 10% ointment have not been fully elucidated, its efficacy in treating EGWs may be attributable to its antioxidant, anti-proliferative, antiviral, and anti-tumor properties.
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