Objectives: Therapeutic vaccines against the Human Papilloma Virus (HPV), the causative agent of cervical cancer, have the potential to stimulate HPV-specific CD8 T cell immune responses. TA-CIN is a single fusion protein comprised of HPV16 E6, E7, and L2 proteins linked in tandem. In preclinical studies, vaccination with TA-CIN induces immunity to HPV16 E6/E7-specific T cell-mediated immune responses and L2-specific neutralizing antibodies in mice. Administration of the vaccine following chemotherapy with cisplatin or radiation was able to improve the therapeutic antitumor effect in a preclinical model compared to vaccination, chemotherapy, or chemoradiation alone (Tseng et al. Cancer Immunol Immunother. 58:737, 2009). This suggests that a therapeutic HPV vaccine may have value in improving the therapeutic effect of the standard care of chemoradiation for patients with cervical cancer. Furthermore, preclinical studies demonstrated that site of administration in the mice influenced the extent of antitumor immunity with vaccination in the hind leg resulting in improved efficacy compared to front leg vaccination (Qiu et al. Virology. 525:205, 2018). This randomized, multi-center study is designed to evaluate the safety and feasibility of administering TA-CIN to patients with HPV-16 associated cervical cancer after completion of definitive primary therapy and assess the immune response when the vaccine is administered in the thigh versus the arm. Methods: Eligible patients for this study have HPV16-related stage IB1-IVA cervical cancer and have completed definitive treatment within the past 12 months. HPV16 nucleic acid within the cervical tumor specimen must be documented by in situ hybridization. Patients must not have evidence of disease recurrence based on prevaccination imaging and clinical assessments within eight weeks of enrollment. Other key eligibility criteria include ECOG performance status ≤1 and absolute lymphocyte count > 500/cu mm. Patients with autoimmune conditions or on immunosuppressive therapy are excluded. Fourteen patients will be randomized to receive up to 3 doses of 100ug TA-CIN vaccine three times to either the arm or the thigh. Immune and clinical responses in patients receiving vaccines will be assessed, and the injection site that elicits more potent immune responses will be selected for future studies. [ABSTRACT FROM AUTHOR]