Introduction /Aim: The World Health Organisation (WHO) in 2013 declared that cervical cancer was the second most common cancer in women globally with a high mortality rate of 52%. More than 99% of cervical cancer cases are caused by sexually-acquired infection with HPV; 50% of the cases are caused by HPV type-16 and 20% by HPV type-18. Currently available vaccines provide highly efficient protection against most common high risk HPV infections but they do not cure current infections. To date, no therapy has been demonstrated to be reliable against cervical cancer due to subsequent toxic side effects that such compounds exert on normal cells when compared to cancer cells and the development of resistance of cancer cells toward such drugs.
Methods: Here we investigated the effect of vaginal delivery of biodegradable PEGylated Lipoplex entrapped Alginate Scaffold (PLAS) loaded with a potent conventional E6E7 siRNA (as they are essential for development of and maintaining malignant transformation in cervical cancer cells) into the vaginal tracts of K14E7 mice (3 doses for 7 days). At 1 hour pre termination, intraperitoneal injection with BrdU was performed to examine actively proliferating cells via immunohistochemistry. Then mice were sacrificed and reproductive tracts were harvested for histological evaluation of E6E7 knockdown cervical cancer cells.
Results: Our results showed a significant reduction in cells undergoing division, hence, a decrease in overall grade of disease.
Conclusion: Our findingsdemonstrated for the first time an siRNA-mediated knockdown of HPV-E7 cancer cells in the vaginal epithelium of K14E7 mice following intravaginal administration of PLAS system. This unique approach for vaginal delivery of siRNA presents a promising targeted intervention for HPV driven cervical cancers as it is more convenient and less invasive therapy for patients compared to current anticancer treatments.