Current Research Topics:
- Investigators in the PRI Group have been involved for more than 25 years in large scale epidemiologic studies of cervical cancer in several countries in Latin America, including case-control studies, cohort studies ad randomized controlled trials of preventive interventions, mainly focusing on cervical and stomach cancers. An extensive collaboration
with the National Cancer Institute of the United States and researchers in Costa Rica has resulted in the establishment of a state-of-the-art research center in Guanacaste, Costa Rica, with ample staff and facilities fully dedicated to cancer research. The Proyecto Epidemiologico Guanacaste
has ample experience in the conduct of different kinds of studies under Good Clinical Practices (GCP) and includes its own study clinics, a large biorepository and cytology, histology, serology, hematology and other laboratories. We also have an active collaboration with the Infection and Cancer Group of the University of Antioquia in Medellin, Colombia and the National Institute of Public Health in Cuernavaca,
Mexico, among other institutions in Latin America.
- The Guanacaste HPV natural history study (NHS) is a prospective, population-based cohort study with participation of a random sample of more than 10,000 women in a high-risk area of Costa Rica who were recruited, screened and followed for more than 7 years beginning in 1993-4. The study has generated a large number of publications and has clarified many aspects of
the natural history of the disease, including epidemiologic, virologic, immunologic and genetic variables. In addition, it has provided extensive information on the validity of different screening methods in the region. A series of ancillary studies were also conducted to further investigate the reasons for the high prevalence of HPV infection in older women,
to evaluate fluctuations of cervical antibody levels with the menstrual cycle and to define the long term outcome of treatment of precancerous lesions.
- The HPV vaccine trial in Guanacaste, Costa Rica, a randomized clinical trial to evaluate the efficacy of the bivalent (HPV16/18) vaccine was initiated in 2004 as a continuation of the NHS. A total of 7,466 women aged 18-25 were recruited and randomised to receive the HPV vaccine or a hepatitis A vaccine as control. Women were screened at yearly intervals and followed 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 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 2,500 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 3 different approaches to triage women with cytologic diagnosis of ASCUS (atypical squamous cells of unknown significance) is underway in Medellin, Colombia.
Approximately 3,000 women with an ASCUS are being 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.
- A screening investigation is being planned to define the best triage strategy for HPV -positive women in screening programs based on HPV testing as the primary modality. There is now a trend for screening programs to transition from cytology to HPV testing as the primary screening method,
but the positive predictive value of the HPV test remains limited because many women with HPV infection do not develop the disease, even when programs are targeted to women over 30 years of age. 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 nearly 100,000 women from several countries, initially in Latin America with collection of appropriate specimens
and strict definition of their cervical diagnosis to evaluate currently available and future triage methods.
- 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 primary screening modality. The initial step in this process is the organization of a large pilot project in the Province of Jujuy, with the collaboration of PRI staff.
- Several countries in Latin America are considering or starting to implement vaccination or HPV testing as primary strategy (e.g., Mexico, Panama, Chile), with active participation of PRI staff.
- In collaboration with the US South West Oncology Group and several centers in Latin America, PRI staff participated in a multicentric trial to evaluate the best alternative as an eradication treatment against Helicobacter pylori. The eradication rate for the different treatments at 6 weeks has been published and the results for 1 year will be reported in the near future, in addition to a series of reports incorporating several biomarkers.
- The association between H pylori and stomach cancer is well established, but interventions based on this knowledge have not been fully developed for implementations in high risk areas. The current information on the impact of eradication of H. pylori on gastric cancer incidence is being evaluated to consider the need for a large multicentre trial with a stomach cancer outcome.
- In the context of the Costa Rica HPV vaccine trial we observed a high prevalence of anal HPV infection among young women. HPV positive women will be followed with periodic virologic and cytologic examinations to investigate the natural history of anal infections and their relation to anal intraepithelial neoplasia.
- Also in the context of the Costa Rica HPV vaccine trial we have evaluated and demonstrated high efficacy of the bivalent vaccine against anal infection. These results will be followed over time to ascertain their potential as anal cancer prevention tools.
- In the Costa Rica vaccine trial, we obtained an oral specimen for HPV testing from all women at their 4-year visit. Despite the lack of baseline oral HPV results, it will be possible to evaluate vaccine efficacy against prevalent
infections in a randomized fashion.