CERVICAL CANCER SCREENING STRATEGIES IN LATIN AMERICA

The third and still ongoing EC-project (Contract # ICA4-CT-2001-10013) is funded by the INCO-DEV Programme and covers the period 2001-2005. This extensive project is participated by 8 research groups from three EC countries (Finland, Italy, Slovenia) and from two Latin American countries (Brazil and Argentina). The official title of the project is: IMPROVING HEALTH SYSTEMS TOWARDS EQUALITY-BASED CONTROL OF CERVICAL CANCER IN LATIN AMERICA. Comparing PAP Smear Cytology, Aided Visual Inspection, Cervicography and Human Papillomavirus (HPV) Testing as Optional Screening Tools in Brazil and Argentina. The project is internationally known as the LAMS Study.

The objective is to elaborate the research data needed to design a cost-effective strategy for cervical cancer screening in Brazil and Argentina, by using a combined cross-sectional (n=12.000) and cohort (n=1.000) study of women examined in four different clinics for the prevalence, pathogenesis and natural history of CIN and HPV infections. The performance characteristics (sensitivity, specificity, negative- and positive predictive value, as well as ROC=receiver operating characteristics) of the traditional diagnostic tools (PAP smear cytology, screening colposcopy) are compared with those of the HPV detection methods (Hybrid Capture II and PCR) and those of the suggested screening tools for low-resource-settings (aided visual inspection, cervicography and self-sampling for HPV) in detecting significant cervical pathology (high-grade CIN lesions and cervical cancer). The long-term objective of this project is to acquire the necessary data for the basis of designing a sustainable and cost-effective strategy for an organised cervical cancer prevention programme in Brazil and Argentina.

This 3-year project is scheduled to proceed a) by establishing the magnitude of cervical cancer and its precursors as a health problem (i.e., prevalence) in target populations at different risk, b) to testing of the performance (sensitivity, specificity, PPV, NPV, ROC) of these optional diagnostic tools, and c) ending up with the synthesis of these data with a feasibility analysis and guidelines, how to improve the health systems by creating a cost-effective strategy for an equality-based cervical cancer control in these two LAM countries.

1. Project Title:

IMPROVING HEALTH SYSTEMS TOWARDS EQUALITY-BASED CONTROL
OF CERVICAL CANCER IN LATIN AMERICA.
Comparing PAP Smear Cytology, Aided Visual Inspection, Cervicography
and Human Papillomavirus (HPV) Testing as Optional
Screening Tools in Brazil and Argentina.
(Contract # ICA4-CT-2001-10013)

 

2.Partner Institutions:

1.Unit of Cytopathology, National Centre of Epidemiology, Surveillance and Promotion of Health, National Institute of Health (ISS), Rome, Italy;

2.Hospital de Clinicas de Porto Alegre, Brazil;

3.Universidade Estadual de Campinas, Campinas, Brazil;

4.Hospital Leonor M de Barros, São Paulo, Brazil;

5.Instituto Adolfo Lutz, São Paulo, Brazil;

6.First Chair Gynecology Hospital de Clinicas, Buenos Aires, Argentina;

7.SIZE Diagnostic Center, Ljubljana, Slovenia;

8.Department of Obstetrics and Gynecology, S.Orsola-Malpighi Hospital, Bologna, Italy;

9.Department of Oral Pathology, Institute of Dentistry, University of Turku, Finland.

 

3.Partners:

Kari J. Syrjänen, Department of Oncology & Radiotherapy, Turku University Hospital, Kiinamyllynkatu 4-8, FIN-20521 Turku, Finland; kari.syrjanen@smwconsultants.fi (COORDINATOR)

Prof. Kari Syrjänen, MD, PhD, FIAC

Mojca Eržen, SIZE Diagnostic Center, Ljubljana, Slovenia; mojca.erzen@volja.net

Prof. Mojca Erzen, MD, PhD, MIAC

Stina Syrjänen, Department of Oral Pathology, Institute of Dentistry, MediCity Research Laboratory, University of Turku, Lemminkäisenkatu 2, FIN-20520 Turku, Finland: stina.syrjanen@utu.fi

Prof. Stina Syrjänen, DDS, PhD

Margherita Branca, Unità Citoistopatologia, Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute, Istituto Superiore di Sanità (ISS), Rome; mbranca@iss.it

Dr. Margherita Branca, MD, PhD, MIAC

Paulo Naud, Hospital de Clinicas de Porto Alegre, Brazil; 3Universidade Estadual de Campinas, Campinas, Brazil; pnaud@naud.com.br (SCIENTIFIC LAM COORDINATOR)

Prof. Paulo Naud, MD, PhD.

Cecilia Roteli-Martins, Hospital Leonor M de Barros, São Paulo, Brazil; ceciliaroteli@terra.com.br

Prof. Cecilia Roteli-Martins, MD, PhD.

Adhemar Longatto-Filho, Instituto Adolfo Lutz, São Paulo, Brazil; longatto-filho@uol.com.br

Dr. Adhemar Longatto-Filho, PhD.

Sophie M. Derchain, Universidade Estadual de Campinas, Campinas, Brazil; derchain@fcm.unicamp.br

Prof. Sophie M. Derchain, MD, PhD.

Silvio Tatti, First Chair Gynecology Hospital de Clinicas, Buenos Aires, Argentina; siltatti@fibertel.com.ar

Prof. Silvio Tatti, MD, PhD.

Luciano Serpa-Hammes, Hospital de Clinicas de Porto Alegre, Brazil; hammes@cpovo.net

Dr. Luciano Serpa Hammes, M.D.

Jean Matos, Hospital de Clinicas de Porto Alegre, Brazil; jcmatos@cpovo.net

Renata Gontijo, Universidade Estadual de Campinas, Campinas, Brazil; rgontijo@terra.com.br

Dr. Renata Gontijo, MD.

Luis Sarian, Universidade Estadual de Campinas, Campinas, Brazil; sarian@terra.com.br

Dr. Luis Sarian, PhD.

Temistokles P. Lima, Hospital Leonor M de Barros, São Paulo, Brazil; pielima.ops@zaz.com.br

Marina Y.S. Maeda, Instituto Adolfo Lutz, São Paulo, Brazil; marinamaeda@hotmail.com

Silvano Costa, Dipertimento di Ginecologia e Ostetrica, Azienda Ospedaliera S. Orsola Malpighi, Bologna; scosta@med.unibo.it

 

4.Abstract:

IMPROVING HEALTH SYSTEMS TOWARDS EQUALITY-BASED CONTROL OF CERVICAL CANCER IN LATIN AMERICA. Comparing PAP Smear Cytology, Aided Visual Inspection, Cervicography and Human Papillomavirus (HPV) Testing as Optional Screening Tools in Brazil and Argentina.

OBJECTIVES: The main objectives are defined as follows

The traditional tools used in screening of cervical cancer include: a) PAP smear cytology, b) colposcopy, and c) biopsy. Optional diagnostic tools suggested to low-resource-setting DEV countries include: 1) aided visual inspection (VIA), 2) cervicography, and 3) testing for HPV. In this project, the feasibility of the traditional and optional diagnostic tools will be tested in target populations at different risk for cervical cancer in two Latin American countries.

• To elucidate the epidemiology, biology and pathogenesis of genital HPV infections, as explanatory factors of the different risk of cervical cancer in different populations (research component).
• Compare the traditional diagnostic techniques 1) with two optional screening tools (aided visual inspection and cervicography) and 2) with HPV typing by Hybrid Capture II and PCR, done a) from conventionally collected samples and b) using self-sampling devices, using the conventional performance tests (sensitivity, specificity, positive- and negative predictive value and ROC analysis).
• The long-term objective is to improve the health systems in these two LAM countries by designing new strategies for a cost-effective, organised programme for cervical cancer control, particularly covering the most vulnerable groups of high-risk women.
  
  ACTIVITIES: The key activities involve:
• This study is a combination of a classical population-based, cross-sectional (prevalence) study and a prospective follow-up (cohort) study of women with different (high and intermediate) risk of cervical cancer.
• During the first 12 months, consecutive series of women (expected n=12.000) attending the partner LAM clinics are screened for cervical HPV infections and CIN, using different diagnostic tools (PAP test, cervicography, aided visual inspection, HPV testing, colposcopy).
• The women with biopsy-confirmed low-grade CIN (HPV-positive or HPV-negative)(=prevalence data) will then comprise the cohorts to be prospectively followed-up until the end of the 38-month project period (=disease prognosis).
• High-grade lesions are promptly treated and followed-up for 36 months. These clinics also collect the epidemiological data by questionnaires focused on the known and suspected risk factors of HPV, CIN and cervical cancer.
• All samples primarily examined in the laboratories of the LAM partners, will be subjected to Quality Control (QC) by the EC partners. Cervical swabs and self-sampling devices (tampons) will be subjected to HPV testing by the Hybrid Capture II, controlled by PCR analysis by the EC partner (=molecular epidemiology). Interlaboratory QC of PAP smear diagnosis will be arranged.
• Cervical biopsies are analysed for a number of factors with potential pathogenetic and prognostic significance (prognostic biomarkers), using immunohistochemistry (IHC) and molecular biological techniques.

EXPECTED OUTCOME: This type of combined cross-sectional and cohort study is focused on the key epidemiological and biological factors of genital HPV infections and cancer precursors in women living in intermediate- and high-risk regions of Brazil and in Argentina. The differences in the incidence of cervical cancer in these LAM regions could be due to two principal causes1) different natural history of the precursor lesions, or 2) due to different level of exposure to the known risk factors, e.g. HPV, HIV, etc. Elucidating the test performance in populations with different prevalence of HPV and CIN is mandatory for planning feasible cervical cancer control strategies for women at different risk of the disease, based on cost-efficacy analysis which will be completed as the final step of the project.

Exploitation of the results has been ongoing for over two years now. Until now, a growing series of important reports have been presented as Congress abstracts, published in scientific journals, are in press or submitted for publication. To see the updated list, click here.

Those who are interested to take a closer look at the study design and the working document of this important research project, can find these documents by making a click here.