In 1993 the authors began an epidemiologic cohort study of the natural history of human Papillomavirus (HPV) infection and cervical neoplasia in a population of low income women in Sao Paulo, Brazil, one of the highest risk areas worldwide for cervical cancer. This study was designed to answer questions that have not yet been addressed in epidemiologic investigations of this neoplastic disease. Although few would dispute that HPV infection is an important cause of cervical cancer, most of the epidemiologic data have come from retrospective studies, which do not provide information on the dynamics of cervical HPV infection in the same individual. The Brazilian cohort study is testing the hypothesis that persistent infections with oncogenic HPV types are more likely to be the true precursor events leading to cervical carcinogenesis. Persistence of infections is being documented on the basis of molecular variants of HPV, which provides a much finer level of detail than simple HPV typing and may unveil in addition to persistence per se other prognostic markers of progression across the spectrum of cervical lesions. The study will accrue 2000 female subjects through February 1996. Subjects are being followed up over a 5 year period in scheduled returns every 4 months, in the first year, and once yearly thereafter, for a total of 8 visits as follows: initial, 4, 8, 12, 24, 36, 48, and 60 months. In each of these visits, subjects are submitted to a questionnaire-based interview, have a cervical specimen taken for Pap cytology and HPV testing, and a blood sample drawn for serologic testing for HPV antibodies. A cervicography is performed once in the first year and at 24 and 48 months. Considering the public health and economic importance of cervical cancer screening and given the current impetus within the federal government to examine the utility of HPV testing in augmenting existing screening programs, the investigators argue that there is a clear need for long-ranging multidisciplinary studies of the natural history of this malignant disease. In brief, this ongoing investigation will further understanding of the etiopathogenesis of cervical neoplasia by tackling the following specific objectives: (1) to study the prevalence and incidence of transient and persistent cervical HPV infection in asymptomatic women; (2) to verify the hypothesis that persistent HPV infection increases risk of low grade and high grade cervical lesions; (3) to search for epidemiologic determinants of persistent cervical HPV infection; (4) to search for specific molecular variants of oncogenic types of HPV that may be associated with an increased risk of cervical neoplasia; (5) to verify the hypothesis that measures of viral burden in the cervix may be correlated with persistent infections and with low and high grade lesions; and (6) to study the humoral immune response to capsid antigens of HPV as a possible marker of persistence of cervical HPV infection and of likelihood of progression in lesion severity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA070269-02
Application #
2517709
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1996-09-11
Project End
1999-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Mcgill University
Department
Type
DUNS #
City
Montreal
State
PQ
Country
Canada
Zip Code
H3 0-G4
Sichero, Laura; El-Zein, Mariam; Nunes, Emily M et al. (2017) Cervical Infection with Cutaneous Beta and Mucosal Alpha Papillomaviruses. Cancer Epidemiol Biomarkers Prev 26:1312-1320
Tota, Joseph E; Ramanakumar, Agnihotram V; Villa, Luisa L et al. (2016) Cervical Infection With Vaccine-Associated Human Papillomavirus (HPV) Genotypes as a Predictor of Acquisition and Clearance of Other HPV Infections. J Infect Dis 214:676-84
Shaw, Eileen; Ramanakumar, Agnihotram V; El-Zein, Mariam et al. (2016) Reproductive and genital health and risk of cervical human papillomavirus infection: results from the Ludwig-McGill cohort study. BMC Infect Dis 16:116
El-Zein, Mariam; Richardson, Lyndsay; Franco, Eduardo L (2016) Cervical cancer screening of HPV vaccinated populations: Cytology, molecular testing, both or none. J Clin Virol 76 Suppl 1:S62-S68
Trottier, Helen; Mayrand, Marie-Hélène; Baggio, Maria Luiza et al. (2015) Risk of Human Papillomavirus (HPV) Infection and Cervical Neoplasia after Pregnancy. BMC Pregnancy Childbirth 15:244
Tota, Joseph E; Ramanakumar, Agnihotram V; Villa, Luisa L et al. (2015) Evaluation of human papillomavirus type replacement postvaccination must account for diagnostic artifacts: masking of HPV52 by HPV16 in anogenital specimens. Cancer Epidemiol Biomarkers Prev 24:286-90
de Araujo-Souza, Patrícia S; Ramanakumar, Agnihotram V; Candeias, João M G et al. (2014) Determinants of baseline seroreactivity to human papillomavirus type 16 in the Ludwig-McGill cohort study. BMC Infect Dis 14:578
Trevisan, Andrea; Schlecht, Nicolas F; Ramanakumar, Agnihotram V et al. (2013) Human papillomavirus type 16 viral load measurement as a predictor of infection clearance. J Gen Virol 94:1850-7
Walter, Stephen D; Riddell, Corinne A; Rabachini, Tatiana et al. (2013) Accuracy of p53 codon 72 polymorphism status determined by multiple laboratory methods: a latent class model analysis. PLoS One 8:e56430
Tota, Joseph E; Ramanakumar, Agnihotram V; Mahmud, Salaheddin M et al. (2013) Cervical human papillomavirus detection is not affected by menstrual phase. Sex Transm Infect 89:202-6

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