HPV co-factors related to the development of cervical cancer: results from a population-based study in Costa Rica

Abstract

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...

A case–control study of endogenous hormones and cervical cancer

“…Use of injectible contraceptives, typically consisting of progesterone only, has also been associated with an increased risk of cervical cancer (Herrero et al, 1990;Hildesheim et al, 2001). Though premeno- pausal women with higher progesterone levels were at a somewhat greater risk of XCIN 2 than women with lower levels, we did not observe clear trends of increasing risk with increasing progesterone level.…”

Determinants of human papillomavirus 16 serological conversion and persistence in a population-based cohort of 10 000 women in Costa Rica

“…Determinants of serologic status All HPV cofactors reported previously in Costa Rica (Hildesheim et al, 2001) were thoroughly investigated with regard to serologic outcomes. Specifically, univariate associations for both outcomes (seroconversion and seropersistence) were assessed for the following behavioural and reproductive variables assessed at enrolment and follow-up via questionnaire: number of sexual partners (lifetime at enrolment, and recent, defined as during the follow-up period and thus includes both previous and new partners), use of oral contraceptives (OCs) (never, former, current), smoking status (never, former, current), early age at first intercourse (defined as o16 years), number of live births and number of pregnancies (lifetime at enrolment and recent, defined as during the follow-up period), years between menarche and sexual debut, and self-reported sexually transmitted diseases.…”

“…As previously described, study enrolment was conducted in 1993 -94 with approval from the NCI and local institutional review boards (Herrero et al, 1997;Hildesheim et al, 2001;Bratti et al, 2004). Briefly, the cohort was a representative sample of the adult female population in Guanacaste, Costa Rica in 1993 -94.…”

Cervical cancer: the sub-Saharan African perspective

“…18 High parity, which is the norm in some cultures in Africa, is also a recognised, independent, HPV-related co-factor for the development of cervical cancer. 18,[20][21][22] Socio-economic factors Worldwide women of low socio-economic status have a greater risk of cervical cancer. Cervical cancer is often referred to as a disease of poverty 23 RI Anorlu / Reproductive Health Matters 2008;16(32): [41][42][43][44][45][46][47][48][49] and of poor women.…”