Here, we demonstrate that electroporation-enhanced immunization with a rationally designed HPV DNA vaccine (GX-188E), preferentially targeting HPV antigens to dendritic cells, elicits a significant E6/E7-specific IFN-γ-producing T-cell response in all nine cervical intraepithelial neoplasia 3 (CIN3) patients. Importantly, eight out of nine patients exhibit an enhanced polyfunctional HPV-specific CD8 T-cell response as shown by an increase in cytolytic activity, proliferative capacity and secretion of effector molecules. Notably, seven out of nine patients display complete regression of their lesions and viral clearance within 36 weeks of follow up. GX-188E administration does not elicit serious vaccine-associated adverse events at all administered doses. These findings indicate that the magnitude of systemic polyfunctional CD8 T-cell response is the main contributing factor for histological, cytological and virological responses, providing valuable insights into the design of therapeutic vaccines for effectively treating persistent infections and cancers in humans.

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The natural history of high-risk human papillomavirus (HRHPV) infection after successful treatment of cervical intraepithelial neoplasia (CIN) is not well known. This study was performed to evaluate the rate and pattern of HRHPV infection clearance after successful conization for CIN and to analyze factors associated with such clearance. A total of 287 patients who underwent loop electrosurgical excision procedures (LEEP) owing to HRHPV-associated CIN were included. All patients had negative resection margins on LEEP specimens and underwent HPV testing with the hybrid capture II system at 3-, 6-, 9-, 12-, 18-and 24-month follow-up visits after LEEP. Persistent HPV infections were detected in 45.6%, 14.3%, 6.3%, 2.2%, 1.5% and 1.1% of patients at 3, 6, 9, 12, 18 and 24 months after LEEP, respectively. Clearance rates did not differ by age, parity or severity of cervical lesion. However, clearance rates were significantly slower in patients with HPV DNA loads >500 RLU/PC before LEEP (p 5 0.040). During 2 years of follow-up after LEEP, 24 patients had recurrent disease revealed by biopsy. The odds ratios for recurrent disease in patients with persistent HRHPV infection increased gradually from 5.17 at the 3-month follow-up visit to 12.54, 15.69 and 25.90 at 6-, 9-, 12-and 24-month follow-up visits, respectively. We conclude that HRHPV infection cleared gradually in most patients within 6 months of treatment. Clearance rates were significantly slower in patients with HPV DNA loads >500 RLU/PC. Persistent HPV infection was a significant positive predictor of recurrence.Cervical cancer is one of the most important health problems in women because this is the second most common female cancer worldwide, with 370,000 cases and 190,000 deaths each year. 1,2 Cervical cancer is preceded by a precancerous lesion, cervical intraepithelial neoplasia (CIN). Human papillomavirus (HPV) infection is the established cause of CIN and cervical cancer. Persistent infection with high-risk HPV types (16,18,31,33,35,39, 45, 51, 52, 56, 58, 59 and 68) is a necessary cause of the vast majority of CIN and cervical cancer cases, and such HPV strains are present in more than 99% of patients. [3][4][5][6] Organized screening systems for cervical cancer with cytologic or HPV tests have reduced the disease incidence. 7 The main role of screening tests is to detect precancerous CIN lesions before they progress to invasive cervical cancer. Effective treatment of CIN and eradication of HPV infection in such patients is important. Today, various conization procedures, such as cold knife conization, laser conization, large loop excision of the transformation zone (LLETZ), and the loop electrosurgical excision procedure (LEEP), have been accepted as gold standards for diagnosis and treatment of CIN. [8][9][10] Several reports have suggested that successful conization also effectively eradicated HPV infections in most patients with CIN, [11][12][13][14][15] and that the persistence of high-risk HPV infection at follow-up was a significant predictor of...