HPV vaccine + imiquimod + metformin

This is an investigational combination therapy comprising three agents—HPV vaccine, imiquimod, and metformin—being studied primarily for the treatment of locally advanced cervical, vaginal, or vulvar carcinoma. The regimen involves intratumoral injection of the FDA-approved quadrivalent HPV-L1 antigen vaccine to stimulate a targeted immune response against tumor cells expressing human papillomavirus antigens. Imiquimod is applied topically or as a suppository; it acts as an immune response modifier by activating innate immunity through Toll-like receptor 7 (TLR7), leading to increased cytokine production and enhanced anti-tumor activity. Metformin is administered orally; it is a biguanide antihyperglycemic agent that also exhibits immunomodulatory and potential anti-cancer effects by improving insulin sensitivity and modulating cellular metabolism. This combination aims to boost tumor-specific immunity during chemoradiation therapy in patients with gynecologic cancers[1][2][3].