The Lancet
Dec 27, 2014 Volume 384 Number 9961 p2173-2266 e67-e69
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Ebola: protection of health-care workers
The Lancet
DOI: http://dx.doi.org/10.1016/S0140-6736(14)62413-2
Summary
The Ebola outbreak in west Africa has taken a substantial toll on health-care workers in Guinea, Liberia, and Sierra Leone—not only doctors and nurses, but also other cadres including ambulance drivers, hospital cleaners, and burial team members. More than 600 of the nearly 17 000 cases of Ebola virus disease have been in health-care workers, more than half of them fatal. In today’s issue of The Lancet we pay tribute to several of the health workers who have lost their lives to the disease since the outbreak began a year ago.

Obituary
Remembering health workers who died from Ebola in 2014
Andrew Green
DOI: http://dx.doi.org/10.1016/S0140-6736(14)62417-X

Comment
HPV vaccination: for women of all ages?
Philip E Castle, Kathleen M Schmeler
Published Online: 01 September 2014
DOI: http://dx.doi.org/10.1016/S0140-6736(14)61230-7
Summary
The discovery of human papillomavirus (HPV) DNA in cervical cancer by Harald zur Hausen sparked 30 years of research that established that persistent cervical infection by certain HPV genotypes causes cervical cancer. This research has led to revolutionary technical advances for the prevention of cervical cancer: prophylactic HPV vaccination and sensitive molecular HPV testing for screening. These promising technologies can be used to complement or enhance established cervical cancer prevention programmes, and to provide robust solutions in low-resource settings without screening programmes.

Comment
Offline: Can Ebola be a route to nation-building?
Richard Horton
DOI: http://dx.doi.org/10.1016/S0140-6736(14)62387-4
Summary
At one of the first meetings of the UN Mission for Ebola Emergency Response, someone is reported to have said that if anyone present wanted to use Ebola as a reason to strengthen health systems they should leave the room. The Ebola response was about one goal and one goal only—getting to zero cases. How times have changed. Last week, WHO convened a High-Level Meeting on Building Resilient Systems for Health in Ebola-Affected Countries. What seems clear now is that Ebola in west Africa is not (only) about Ebola.

Articles
Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study
S Rachel Skinner, PhD, Anne Szarewski, PhD, Prof Barbara Romanowski, MD, Prof Suzanne M arland, FRCPA, Prof Eduardo Lazcano-Ponce, PhD, Prof Jorge Salmerón, PhD, M Rowena Del Rosario-Raymundo, MD, Prof René H M Verheijen, MD, Swee Chong Quek, MBBCh, Daniel P da Silva, MD, Prof Henry Kitchener, MD, Kah Leng Fong, MRCOG, Céline Bouchard, FRCSC, Prof Deborah M Money, MD, Arunachalam Ilancheran, MD, Prof Margaret E Cruickshank, MD, Prof Myron J Levin, MD, Prof Archana Chatterjee, MD, Prof Jack T Stapleton, MD, Mark Martens, MD,
Wim Quint, PhD, Marie-Pierre David, MSc, Dorothée Meric, MSc, Karin Hardt, PhD, Dominique Descamps, MD, Brecht Geeraerts, PhD, Frank Struyf, MD, Gary Dubin, MD, for the VIVIANE tudy Group Dr Szarewski died in August, 2013
Published Online: 01 September 2014
DOI: http://dx.doi.org/10.1016/S0140-6736(14)60920-X
Summary
Background
Although adolescent girls are the main population for prophylactic human papillomavirus (HPV) vaccines, adult women who remain at risk of cervical cancer can also be vaccinated. We report data from the interim analysis of the ongoing VIVIANE study, the aim of which is to assess the efficacy, safety, and immunogenicity of the HPV 16/18 AS04-adjuvanted vaccine in adult women.
Methods
In this phase 3, multinational, double-blind, randomised controlled trial, we randomly assigned healthy women older than 25 years to the HPV 16/18 vaccine or control (1:1), via an internet-based system with an algorithm process that accounted for region, age stratum, baseline HPV DNA status, HPV 16/18 serostatus, and cytology. Enrolment was age-stratified, with about 45% of participants in each of the 26–35 and 36–45 years age strata and 10% in the 46 years and older stratum. Up to 15% of women in each age stratum could have a history of HPV infection or disease. The primary endpoint was vaccine efficacy against 6-month persistent infection or cervical intraepithelial neoplasia grade 1 or higher (CIN1+) associated with HPV 16/18. The primary analysis was done in the according-to-protocol cohort for efficacy, which consists of women who received all three vaccine or control doses, had negative or low-grade cytology at baseline, and had no history of HPV disease. Secondary analyses included vaccine efficacy against non-vaccine oncogenic HPV types. Mean follow-up time was 40•3 months. This study is registered with ClinicalTrials.gov, number NCT00294047.
Findings
The first participant was enrolled on Feb 16, 2006, and the last study visit for the present analysis took place on Dec 10, 2010; 5752 women were included in the total vaccinated cohort (n=2881 vaccine, n=2871 control), and 4505 in the according-to-protocol cohort for efficacy (n=2264 vaccine, n=2241 control). Vaccine efficacy against HPV 16/18-related 6-month persistent infection or CIN1+ was significant in all age groups combined (81•1%, 97•7% CI 52•1–94•0), in the 26–35 years age group (83•5%, 45•0–96•8), and in the 36–45 years age group (77•2%, 2•8–96•9); no cases were seen in women aged 46 years and older. Vaccine efficacy against atypical squamous cells of undetermined significance or greater associated with HPV 16/18 was also significant. We also noted significant cross-protective vaccine efficacy against 6-month persistent infection with HPV 31 (79•1%, 97•7% CI 27•6–95•9) and HPV 45 (76•9%, 18•5–95•6]) Serious adverse events occurred in 285 (10%) of 2881 women in the vaccine group and 267 (9%) of 2871 in the control group; five (<1%) and eight (<1%) of these events, respectively, were believed to be related to vaccination.
Interpretation
In women older than 25 years, the HPV 16/18 vaccine is efficacious against infections and cervical abnormalities associated with the vaccine types, as well as infections with the non-vaccine HPV types 31 and 45.

Viewpoint
Improving the assessment and attribution of effects of development assistance for health
Nour Ataya, MPH, Christoph Aluttis, MSc, Prof Antoine Flahault, PhD, Prof Rifat Atun, FRCP, Prof Andy Haines, FMedSci
Published Online: 25 June 2014
DOI: http://dx.doi.org/10.1016/S0140-6736(14)60791-1
Summary
Overseas development assistance for health (DAH) increased substantially from 2000, but has plateaued since 2010 because of the global economic crisis,1 with growing public demands for funders and beneficiary countries to show the effect of investments.2–5 When showing effect, donor agencies and countries need to address two challenges: first, accurate estimation of the effects of investments in different areas (eg, vaccines or health systems) on health outcomes; and second, attribution of the effects to specific investments.