Prevention and Implementation Group
Current Research Topics
- The human papillomavirus (HPV) vaccine trial in Guanacaste, Costa Rica, a randomized clinical trial to evaluate the efficacy of the bivalent (HPV 16/18) vaccine, was initiated in 2004 in collaboration with Costa Rican investigators and the United States National Cancer Institute. A total of 7466 women aged 18-25 years were recruited and randomized to receive the HPV vaccine or a hepatitis A virus vaccine as control. The study confirmed the efficacy of the bivalent vaccine against HPV 16 and 18 and described its cross-protection against HPV 31, 33, and 45 and that the vaccine efficacy against HPV 16 and 18 was equally good among women who received one, two, and three doses, whereas there was no efficacy among women who were HPV-positive at the time of vaccination. As a continuation of that effort, PRI is collaborating in the ESCUDDO Study, which will formally assess the non-inferiority of one dose of each of the HPV vaccines (bivalent and nonavalent) compared with two doses. The study will recruit 20 000 adolescent girls aged 12-16 years, who will be randomized to each of the four arms. In addition, a population sample of women aged 17-20 years will be recruited to document HPV infection and estimate vaccine efficacy. Reducing the number of doses may not be efficient for a vaccination programme to be successful. In fact, in countries like France, additional measures are needed to increase coverage (currently below 30%), to achieve programme goals. PRI is conducting the PAPRICA project, an educational intervention based on a behavioural change model, among general practitioners in Lyon, aiming to increase doctor-patient communication and consulted-shared decision-making that may translate into more girls being vaccinated. It is expected that PAPRICA can become a model to disseminate other prevention messages to different target groups.
- The multicentre study of cervical cancer screening and triage with HPV testing (ESTAMPA study) is a large screening investigation aiming to define the best triage strategy for HPV-positive women in screening programmes based on HPV testing as the primary modality. There is now a trend for screening programmes to transition from cytology to HPV testing as the primary screening method. However, the positive predictive value of the HPV test remains limited because many women with HPV infection do not develop the disease, even when programmes are targeted to women older than 30 years. It is necessary to investigate the usefulness of a series of triage techniques, from visual inspection and cytology to a series of new biomarkers based on detection of DNA, RNA, proteins, or other markers of transformation. The plan is to recruit 50 000 women from several countries in Latin America, with collection of several specimens and strict definition of their cervical diagnosis, to evaluate currently available and future triage methods. In addition, the study will also describe the challenges encountered when setting up an HPV-based cervical screening programme and will propose approaches to implement sustainable programmes in different scenarios. Several ancillary studies are also being considered, such as: (1) evaluating the psychosocial impact of HPV test results in Latin American populations, (2) assessing the knowledge and attitudes about HPV in individuals and health personnel in the communities where the study is being conducted, (3) evaluating the effect of cervical disease biomarkers on colposcopic findings, and (4) performing cost-benefit evaluation of different screening strategies for different countries, among others.
- Argentina is one of the countries that is starting to vaccinate young women with the HPV vaccine and at the same time is implementing HPV testing as the primary screening modality. With the collaboration of PRI staff, a large population-based screening project in Jujuy Province using HPV testing followed by cytology triage was initiated in 2012 and is now expanding to other provinces in Argentina. Furthermore, the acceptability and feasibility of using self-sampled HPV testing within a screening programme have been evaluated in a randomized nested study in the same Jujuy population. The study demonstrated a 4-fold increase in participation when community health workers invited women to self-collect their HPV tests compared with attending a clinic.
Watch Video – “Proyecto EMA (Evaluación Modalidad Autónoma) | Conocimiento para la salud de las mujeres.“
- Under a Collaborative Programme between PRI and the Department of Reproductive Health and Research of the World Health Organization (RHR/WHO), PRI staff are evaluating the implementation of rapid HPV testing at the primary and secondary care levels in the United Republic of Tanzania. In addition, PRI is carrying out the CESTA study, aiming to provide clear evidence on the benefits, side-effects, and cost-effectiveness of two screen-and-treat algorithms that are recommended in the most recent update of the WHO Comprehensive Cervical Cancer Control (C4-GEP) guide, notably (i) HPV test, triage by VIA, and treat (ablative treatment); and (ii) HPV test and treat. The acceptability and side-effects of cryotherapy and thermal ablation will also be investigated.
- In December 2013, a Working Group convened by IARC reviewed evidence regarding Helicobacter pylori eradication strategies for gastric cancer prevention. The participants concluded that gastric cancer′s enormous global burden and the feasibility of treating its principal cause make it a logical target for intervention. They called for health agencies in countries with high rates of gastric cancer to focus more public health resources on gastric cancer by including it within their national cancer control programmes and by assessing current and future human and economic impacts of this condition and the potential value of preventing it. Within the next 10 years, results from several ongoing randomized trials are likely to resolve many of the uncertainties about H. pylori screening and treatment. Nevertheless, practical questions about the implementation and outcomes of population-based gastric cancer prevention programmes could best be answered by direct observation in the communities where they are applied. It is therefore urged that countries consider implementing demonstration programmes of H. pylori screening and eradication now. To determine whether and how to undertake such programmes, health authorities will require data for their populations on gastric cancer rates and prevalence of H. pylori infection, information that also may identify subpopulations at particularly elevated risk (e.g. immigrants from high-risk countries). From a practical standpoint, many countries will first need to develop more effective systems for tabulating causes of death and for cancer registration. Locally derived data on antibiotic resistance in H. pylori, effectiveness of treatment regimens, and re-infection rates will also be useful for planning.
- PRI staff are conducting the ENIGMA study to investigate the epidemiology of H. pylori and the prevalence of cofactors in high- and low-risk areas for gastric cancer around the world. Population-based samples of subjects aged 1-65 years are being recruited for an extensive interview on risk factors and collection of blood, urine, and faeces, to define the age-specific prevalence of H. pylori infection as well as the prevalence of cofactors and to investigate antibiotic resistance patterns and other microbial characteristics. Endoscopy is planned in a sample of the participants, to establish the prevalence of gastric abnormalities and to further investigate characteristics of the bacterial strains that could explain the extreme regional differences in gastric cancer incidence.
- In collaboration with the National Cancer Center, Republic of Korea (NCC), in order to define the role of H. pylori eradication in the prevention of gastric cancer and its precursors, PRI staff are conducting a randomized controlled clinical trial within the national gastric cancer screening programme in the Republic of Korea (HELPER study). The study is recruiting 11 000 men and women aged 40-60 years, who undergo endoscopy with biopsies for screening. The presence of H. pylori is ascertained on the biopsies, and subjects positive for H. pylori are being randomized to receive quadruple H. pylori eradication therapy or placebo. All participants independently of their H. pylori result will be routinely screened every 2 years under the national screening programme and will be followed up for 10 years.
- The current European gastric cancer screening guidelines propose the use of pepsinogen testing followed by endoscopy as a screening scheme for gastric cancer in high-risk areas. PRI staff have designed a randomized study (GISTAR) in collaboration with the University of Latvia to evaluate whether the use of pepsinogen and H. pylori testing is effective in identifying high-risk subjects to be referred to appropriate treatment, thus eventually reducing gastric cancer mortality. Participants will be randomized to the intervention arm, which includes testing for both markers followed by endoscopy in pepsinogen positives and eradication treatment in H. pylori positives, or to routine care (no screening). The aim is to recruit 30 000 subjects aged 40-64 years in Latvia, Belarus, and the Russian Federation. All participants are being offered colorectal cancer screening through the faecal immunochemical test (FIT) independently of randomization arm. A pilot of 3000 subjects has been completed in Latvia to evaluate the acceptability of the screening scheme and the feasibility of implementing the study using the local health infrastructure.