The Lancet
Nov 21, 2015 Volume 386 Number 10008 p2029-2116
http://www.thelancet.com/journals/lancet/issue/current

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Editorial
Violence against women and girls: how far have we come?
The Lancet
DOI: http://dx.doi.org/10.1016/S0140-6736(15)01029-6
Summary
A year ago, The Lancet published a Series on violence against women and girls ahead of the International Day for the Elimination of Violence against Women on Nov 25. The day marks the start of the 16 Days of Activism against Gender-Based Violence, which this year, for the first time, has prevention as its theme. This focus is encouraging. One in three women will experience physical and/or sexual violence in their lifetime but, as evidence in the Series showed, such violence is preventable. The authors found that community and group interventions involving men and women can shift entrenched social norms and attitudes to reduce the risk of violence against women and girls, but concerted efforts were needed for change

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Comment
Towards therapeutic vaccination against cervical precancer?
Mark Schiffman, Nicolas Wentzensen
Published Online: 16 September 2015
DOI: http://dx.doi.org/10.1016/S0140-6736(15)00240-8
Summary
In The Lancet, Cornelia Trimble and colleagues1 report the results of a double-blind, randomised controlled trial of therapeutic human papillomavirus (HPV) vaccination. Three doses of an intramuscular HPV-16 and HPV-18 plasmid vaccine significantly increased histological regression of cervical precancers caused by HPV types 16 and 18. At 36 weeks after the first dose, regression of cervical intraepithelial neoplasia 2/3 was 48·2% compared with a spontaneous rate in the placebo group of 30·0% (difference 18·2%, 95% CI 1·3–34·4).

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Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial
Cornelia L Trimble, Matthew P Morrow, Kimberly A Kraynyak, Xuefei Shen, Michael Dallas, Jian Yan, Lance Edwards, R Lamar Parker, Lynette Denny, Mary Giffear, Ami Shah Brown, Kathleen Marcozzi-Pierce, Divya Shah, Anna M Slager, Albert J Sylvester, Amir Khan, Kate E Broderick, Robert J Juba, Timothy A Herring, Jean Boyer, Jessica Lee, Niranjan Y Sardesai, David B Weiner, Mark L Bagarazzi
Summary
Background
Despite preventive vaccines for oncogenic human papillomaviruses (HPVs), cervical intraepithelial neoplasia (CIN) is common, and current treatments are ablative and can lead to long-term reproductive morbidity. We assessed whether VGX-3100, synthetic plasmids targeting HPV-16 and HPV-18 E6 and E7 proteins, delivered by electroporation, would cause histopathological regression in women with CIN2/3.
Methods
Efficacy, safety, and immunogenicity of VGX-3100 were assessed in CIN2/3 associated with HPV-16 and HPV-18, in a randomised, double-blind, placebo-controlled phase 2b study. Patients from 36 academic and private gynaecology practices in seven countries were randomised (3:1) to receive 6 mg VGX-3100 or placebo (1 mL), given intramuscularly at 0, 4, and 12 weeks. Randomisation was stratified by age (<25 vs ≥25 years) and CIN2 versus CIN3 by computer-generated allocation sequence (block size 4). Funder and site personnel, participants, and pathologists were masked to treatment. The primary efficacy endpoint was regression to CIN1 or normal pathology 36 weeks after the first dose. Per-protocol and modified intention-to-treat analyses were based on patients receiving three doses without protocol violations, and on patients receiving at least one dose, respectively. The safety population included all patients who received at least one dose. The trial is registered at ClinicalTrials.gov (number NCT01304524) and EudraCT (number 2012-001334-33).
Findings
Between Oct 19, 2011, and July 30, 2013, 167 patients received either VGX-3100 (n=125) or placebo (n=42). In the per-protocol analysis 53 (49·5%) of 107 VGX-3100 recipients and 11 (30·6%) of 36 placebo recipients had histopathological regression (percentage point difference 19·0 [95% CI 1·4–36·6]; p=0·034). In the modified intention-to-treat analysis 55 (48·2%) of 114 VGX-3100 recipients and 12 (30·0%) of 40 placebo recipients had histopathological regression (percentage point difference 18·2 [95% CI 1·3–34·4]; p=0·034). Injection-site reactions occurred in most patients, but only erythema was significantly more common in the VGX-3100 group (98/125, 78·4%) than in the placebo group (24/42, 57·1%; percentage point difference 21·3 [95% CI 5·3–37·8]; p=0·007).
Interpretation
VGX-3100 is the first therapeutic vaccine to show efficacy against CIN2/3 associated with HPV-16 and HPV-18. VGX-3100 could present a non-surgical therapeutic option for CIN2/3, changing the treatment outlook for this common disease.
Funding
Inovio Pharmaceuticals.