Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial.

BACKGROUND: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. METHODS: A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. RESULTS: In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. CONCLUSIONS: The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18-associated high-grade genital lesions and persistent infection in women.

[Role of HPV16/18/45 DNA testing of cervical specimens as a triage testing in cervical cancer screening].

OBJECTIVE: To evaluate the clinical performance of careHPV16/18/45 DNA testing of cervical specimens as a triage testing for women with positive findings during the cervical cancer screening. METHODS: Eligible women aged 25-65 years were enrolled from two high-risk communities in Yangcheng County,Shanxi Province.After providing written informed consent on a voluntary base,women underwent questionnaire-based interview,gynecological examination,and sample collection.Hybrid capture 2 technology(HC2),careHPV,Avantage HPV E6 test,and visual inspection with acetic acid(VIA)were conducted as the primary screening tests at the enrollment visit.Women with any positive finding were invited to receive a second VIA and colposcopy.careHPV16/18/45 was performed as a triage testing.Any visible lesion under colposcopy was directly biopsied.Women with pathology confirmed cervical intraepithelial neoplasia grade 2 and worse(CIN2+)were treated with standard procedures. RESULTS: For the self-collected and doctor-collected samples,the application of careHPV16/18/45 as a triage testing decreased the colposcopy referral to 3.2% and 3.1%,respectively.Meanwhile,the sensitivity,specificity,and positive predictive value(PPV)for CIN2+were 50.0%,97.6%,and 26.7% for women with positive self-sampling careHPV results and 63.0%,97.9%,and 34.0% for women with positive doctor-sampling careHPV results. CONCLUSION: careHPV16/18/45 is promising as a triage testing among women with positive screening findings in low-resource settings.