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 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. Women were screened at yearly intervals and followed up initially for 4 years. At the end of follow-up, all women had received the vaccine they had not received at recruitment (crossover) plus hepatitis B virus vaccine as an additional benefit. 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. In addition, in stratified analyses, it showed the decline in vaccine efficacy at the population level with increasing age. One of the most interesting findings was the observation that HPV vaccine efficacy against HPV 16 and 18 was equally good among women who received one, two, and three doses, while there was no efficacy among women who were positive at the time of vaccination. Current plans include long-term follow-up of the vaccinated cohort. Given the fact that all women have now received the HPV vaccine, a new unvaccinated control group of about 2500 women was recently recruited to continue the evaluation of efficacy and safety over 10 years.
- The ASCUS project in Antioquia, Colombia, is conducted in collaboration with the Cancer and Infection group of the University of Antioquia in Colombia. It is a randomized clinical trial of three different approaches to triage women with a cytological diagnosis of ASCUS (atypical squamous cells of unknown significance) that is under way in Medellín, Colombia. Approximately 3000 women with ASCUS were recruited and randomized to immediate colposcopy, repeat cytology, or HPV testing. It is anticipated that the study will provide information on how to manage this frequent diagnosis in the context of the Colombian health system.
- 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, (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 Prevention and Implementation Group (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.
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- 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 and are designing a large randomized study to evaluate different screen-and-treat approaches suitable for African countries.
- 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 United States Southwest Oncology Group and several centres in Latin America, PRI staff participated in a multicentre trial to evaluate the best alternative as an eradication treatment against H. pylori. The eradication rate for the different treatments at 6 weeks has been published, and the results for 1 year will be reported soon, in addition to a series of reports incorporating several biomarkers.
- 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 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 initiated in Latvia to evaluate the acceptability of the screening scheme and the feasibility of implementing the study using the local health infrastructure.
- In the context of the Costa Rica HPV vaccine trial, a high prevalence of anal HPV infection was observed among young women. HPV-positive women are being followed up with periodic virological and cytological examinations to investigate the natural history of anal infections and their relationship to anal intraepithelial neoplasia.
- Also in the context of the Costa Rica HPV vaccine trial, PRI staff have evaluated and demonstrated high efficacy of the bivalent vaccine against anal infection. These results will be followed over time to ascertain the potential of HPV vaccines as anal cancer prevention tools.