We confirm the early decline of HPV infection with age but note increased prevalence after menopause, which could be related to a second peak of HSILs, an observation that warrants further investigation. At least 80% of HPVs involved in cervical carcinogenesis in this population have been characterized. Polyvalent vaccines including the main cancer-associated HPV types may be able to prevent most cases of cervical disease in this region.

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This paper reports on the enrollment phase of a population-based natural history study of cervical neoplasia in Guanacaste, a rural province of Costa Rica with consistently high rates of invasive cervical cancer. The main goals of the study are to investigate the role of human papillomavirus (HPV) infection and its co-factors in the etiology of high-grade cervical neoplasia, and to evaluate new cervical cancer screening technologies. To begin, a random sample of censal segments was selected and enumeration of all resident women 18 years of age and over was conducted with the aid of outreach workers of the Costa Rican Ministry of Health. Of the 10 738 women who were eligible to participate, 10 049 (93.6%) were interviewed after giving written informed consent. After the interview on cervical cancer risk factors was administered, a pelvic examination was performed on those women who reported previous sexual activity. The pelvic examination included a vaginal pH determination and collection of cervical cells for cytologic diagnosis using three different techniques. Additional cervical cells were collected for determination of the presence and amount of DNA from 16 different types of HPV, and two photographic images of the cervix were taken and interpreted offsite by an expert colposcopist. Finally, blood samples were collected for immunologic and micronutrient assays. Women with any abnormal cytologic diagnosis or a positive Cervigram, as well as a sample of the whole group, were referred for colposcopy, and biopsies were taken when lesions were observed. The enrollment screening will serve as the basis for a prevalent case-control study, and the members of the cohort free from serious disease will be followed actively, at intervals of no more than a year, to study the natural history of HPV infection and the origins of high-grade squamous intraepithelial lesions (HSIL). Details of the field operation are outlined, with particular reference to the realization of this kind of study in developing countries. Descriptive data on the prevalence of disease and exposure to various risk factors are also presented.

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The vast majority of cervical cancer cases are attributable to human papillomavirus (HPV) infection (Bosch et al, 1995;Schiffman et al, 1996;Nobbenhuis et al, 1999;Herrero et al, 2000). Our current challenge is to identify factors involved in the rare progression of HPV infection, which is common and usually benign, to cervical cancer and its immediate precursor, high-grade squamous intraepithelial lesions (HSIL).Results from studies of HPV 'co-factors' suggest that reproductive factors, contraceptive use, cigarette smoking, and correlates of sexual behaviour other than HPV infection might be associated with HSIL and cervical cancer (henceforth referred to as HSIL/CA) (Bosch et al, 1992;Munoz et al, 1993;Becker et al, 1994;Moreno et al, 1995;Kjaer et al, 1996;Chaouki et al, 1998;Chichareon et al, 1998;Ho et al, 1998;Kruger-Kjaer et al, 1998;Olsen et al, 1998;Ngelangel et al, 1998;Roteli-Martins et al, 1998). In most of these studies, HPV infection was accounted for through statistical adjustment, i.e. by averaging the impact of other factors in HPV-negative and HPV-positive cases and controls. Given strong association between HPV and HSIL/CA (relative risks of ≥ 50), it is unclear whether effects observed for co-factors (relative risks usually < 3) in these previous studies are real or due to residual confounding by HPV.To address this concern, we conducted a prevalent case-control study within a 10 077 woman population-based study in Guanacaste, Costa Rica. We evaluated factors associated with progression of HPV infection and its early cytologic manifestation (LSIL) by comparing 146 HPV-positive cases of HSIL/CA against a group of 843 HPV-positive cohort members who did not have concurrent HSIL/CA. We chose our control group to include only non-cases (not diagnosed with HSIL) that were truly at risk of becoming a case (infected with HPV). Although this study design likely attenuated the associations of cofactors that are associated with the acquisition and possible persistence of infection, it avoided potential residual confounding by HPV. Thus, by including only HPVinfected women in a strictly population-based study, we were better able to estimate properly the role of possible HPV cofactors. METHODS Cohort baseA population-based cohort was established in Guanacaste, Costa Rica in 1993/4 (Herrero et al, 1997. The study was conducted after approval by the NCI and local institutional review boards, and all participants provided informed consent. Cluster sampling was utilized to select a representative sample of the adult female population of Guanacaste (n = 10 738 eligible women). 10 049 women (94% of eligibles) agreed to visit one of our study clinics. Because few women were expected to have Summary We examined factors associated with high-grade squamous intraepithelial lesions (HSIL) and cervical cancer among human papillomavirus (HPV)-infected women in a prevalent case-control study conducted within a population-based cohort of 10 077 women in Costa Rica. We compared 146 women with HPV-positive HSIL or cance...