Human papillomavirus (HPV) therapeutic vaccine development and ongoing clinical trials have revealed viral elimination and the waning of cervical intraepithelial neoplasia (CIN) and cervical cancer. HPV therapeutic vaccines are aimed at treating advanced cancers and pre‑cancerous lesions by generating antibodies and cell‑mediated immunity. The efficacy of a novel high‑risk HPV‑16/18 therapeutic vaccine in treating CIN and cervical cancer was systematically assessed. A total of three databases from 2012 to 2022 were systematically searched. Scopus (https://www.scopus.com/home.uri), PubMed (https://pubmed.ncbi.nlm.nih.gov/), Hinari (https://portal.research4life.org/) and Google Scholar were searched. Original articles conducted in human clinical trials were included based on a predefined inclusion criterion. The Joanna Briggs Institute (JBI) Critical Appraisal tools was utilized for use in the JBI Systematic Reviews Checklist for Systematic Reviews and Research Syntheses (http://joannabriggs.org/research/critical‑appraisal‑tools.html) to assess the risk of bias (RoB). Moreover, five authors worked independently during evidence searching and reached a consensus on all included studies to avoid the RoB. Data were extracted and synthesized from the included studies using an Excel spread sheet. The Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) guidelines were used to select studies and a random model effect was also used to analyze the outcome of the review [I2=0.00%, P=0.93, confidence interval 95%(CI)]. Only eight evidences were included out of 555 studies searched. The efficacy of the novel HR‑HPV 16/18 therapeutic vaccine among 377 women suffering from high‑grade CIN and cervical cancer was 88.33% (333/377). Vaccination was most efficacious (33%, 126/377) and least efficacious (23%, 87/377) in complete lesion regression and partial lesion regression, respectively. However, 12% of the women progressed to cancer. Additionally, 33% (126/377) and 23% (87/377) of women demonstrated complete viral clearance and viral load reduction, respectively. Complete lesion regression and progression of lesion to cancer have the highest and lowest effect sizes: 33% (I²=0.00%, P=0.93, 95% CI=0.60‑60.67), 22% (I²=0.00%, P=0.93, 95% CI=11.40‑55.40), and respectively. The overall effect size of the clinical trial outcome is 27.67% (I²=0.00%, P=0.93, 95% CI=14.30‑41.03). The efficacy of a novel HR‑HPV 16/18 therapeutic vaccine is very promising for high‑grade CIN and cervical cancer therapy. Further studies are urgently required to boost the efficacy of a novel HR‑HPV 16/18 therapeutic vaccine, reduce women's health burden, and improve the quality of human life.

Related Articles