Background: The prognosis for patients with relapsed/refractory advanced cervical cancer is dismal with a 5-year survival rate of 17%. Limited treatment options were available including platin based therapy, antiangiogenic therapy and immune therapy. Immune checkpoint blockage with anti-programmed cell death 1 (PD-1) antibodies had an overall response rate of 17% among a minority of patients. Recently a phase II study showed human papillomavirus (HPV) 16 vaccination amplified PD-1 antibodies in incurable HPV16 positive cancer with an ORR of 33%. But the study enrolled majority were oropharyngeal cancer patients (92%). Here, we designed and conducted phase II clinical trial to assess the efficacy and safety of combining anti-PD-1 antibody and HPV vaccination for patients with relapsed/refract cervical cancer. Methods: In this single-arm, single-center phase II clinical trial, patients with relapsed/refract cervical cancer were registered (NCT04096911) and enrolled from Dec, 2019 to Dec, 2022 in Department of Oncology, Northern Jiangsu People's Hospital, Yangzhou, China. All patients received prior radiation therapy and had at least one or more lines of therapies. Duration of follow up for censored patients was 36 months. The recombinant human papillomavirus quadrivalent vaccine (0.5ml) was given subcutaneously on day 0, third month, and 6^th month. Anti-PD-1 antibody, 200mg was given intravenously every 3 weeks starting on day 1 for up to 2 years. Results: As of Dec 21, 2022, thirteen patients were enrolled in the trial. The median age was 55 years (range, 52 to 83 years). The overall response rate was 69.2%. Disease control rate was 84.9%. Median duration of response was 7.07 months (95%CI, 1.94 to 15.8 month). Six patients achieved complete response. Median overall survival was 13.96 month. No grade 3 and 4 toxicity occurred. Conclusions: Our study was the first clinical trial using HPV vaccine as therapeutic agent in advance cervical cancer treatment. Up to date, immunotherapy along in cervical cancer had limited response rate less than 20% and the combination therapies was less than 40%. In our study, the overall response of 69.2%, disease control rate of 84.9% and median overall survival of 13.96 months were significantly higher compared with anti-PD-1 antibody alone or any current available regiment combinations in relapsed/refract advance cervical cancer patients. We also found synergistic effect of T cell and B cell plays an important role in our study. It appears neoantigen associated with tumor was easier to initiate immune response in cervical cancer patients. This is the first time to show employing combined immune therapeutic agents only is a novel effective clinical strategy in relapsed/refract advance cervical cancer. Clinical trial information: NCT04096911.