Dietary consumption of antioxidant nutrients and risk of incident cervical intraepithelial neoplasia.

OBJECTIVE: Women with human papillomavirus (HPV) infections are at risk for developing squamous intraepithelial lesions (SIL) of the cervix; however, other factors are required for infections to progress to SIL. We hypothesize that consumption of fruits and vegetables high in antioxidant nutrients may prevent, in part, the development of HPV-associated SIL. METHODS: This study is a nested case-control study of 265 HPV-positive women (93 SIL cases and 172 cytologically normal controls) in the Ludwig-McGill Cohort Study, São Paulo, Brazil. Diet was assessed by a self-administered food frequency questionnaire. The association between food and nutrient intake of antioxidants and incident SIL was determined by logistic regression and multinomial regression when comparing LSIL and HSILs. RESULTS: Higher reported consumption of papaya was inversely associated with risk of SIL (p trend=0.01) and strongest for >or=1 time/week (adjusted odds ratios (AORs)=0.19; 95%CI, 0.08-0.49). Risk of SIL was reduced among women reporting consumption of oranges >or=1 time/week (AOR=0.32; 95%CI, 0.12-0.87; p-trend=0.02). Nutrient intakes of ss-cryptoxanthin and alpha-carotene were marginally protective against SIL. CONCLUSIONS: Frequent consumption of fruits high in antioxidant nutrients appears to be associated with reduced risk of incident SIL among Brazilian women.

No association between endogenous retinoic acid and human papillomavirus clearance or incident cervical lesions in Brazilian women.

Although oncogenic human papillomavirus (HPV) infections have been established as the necessary cause of cervical cancer, most HPV infections are transient and rarely progress to squamous cervical lesions. The activity of HPV is tightly associated with epithelial cell differentiation; therefore, regulators of differentiation, such as retinoic acid (RA), have been considered targets for the prevention of HPV-associated squamous intraepithelial lesion (SIL) development. The purpose of this study was to determine the association between circulating RA and early events in cervical carcinogenesis, specifically type-specific HPV clearance and SIL detection. Archived blood samples from 643 women participating in the Ludwig-McGill Cohort in São Paulo, Brazil, were analyzed by high-pressure liquid chromatography for three RA isomers (all-trans, 13-cis, and 9-cis-RA). A type-specific HPV clearance event was defined as two consecutive visits negative for an HPV type during follow-up for 364 HPV-positive women. Among the 643 women in this analysis, 78 were diagnosed with incident SIL. The probability of clearing an oncogenic HPV infection was not significantly different across RA isomer quartiles. There was a suggestion that increasing all-trans-RA increased the rate of nononcogenic HPV clearance (P-trend = 0.05). There was no association observed between serum RA levels and incident SIL. Our results suggest that elevated circulating RA isomer levels do not increase the rate of HPV clearance or reduce the risk of incident SIL. The role of RA in the inhibition of HPV-induced carcinogenesis, as shown in vitro, lacks confirmatory evidence within epidemiologic studies among women.

Temporal variation and identification of factors associated with endogenous retinoic acid isomers in serum from Brazilian women.

OBJECTIVE: Retinoids (natural and synthetic derivatives of vitamin A) have cancer chemotherapeutic and chemopreventive activities. Retinoic acid (RA) treatment has been associated with significant regression of preneoplastic lesions. However, serious toxicity associated with some therapies has made long-term chemoprevention in healthy populations unfeasible. Recently, serum RA has been shown to increase in response to oral retinol (vitamin A) supplementation. Here, we assess the variability of circulating RA levels and the lifestyle, demographic, and nutritional factors that explain such variability. METHOD: Total RA concentration and the concentrations of RA isomers (all-trans-RA, 13-cis-RA, and 9-cis-RA) were measured by high-pressure liquid chromatography in serum samples obtained 4 months apart from 502 women participating in the Ludwig-McGill Cohort (Sao Paulo, Brazil). RESULTS: The relative abundance of the three RA isomers was similar for each visit (baseline and month 4), with 13-cis-RA having the highest concentrations followed by 9-cis-RA and all-trans-RA. The within-person variability of total RA and individual isomers was low. Using multivariate logistic regression models (upper tertile versus low/middle tertile of serum RA), we found that age, race, oral contraceptive use, total number of pregnancies, and season of initial blood draw were significantly associated with at least one endogenous RA isomer level. All endogenous RA isomers were positively associated with serum retinol, beta-carotene, and beta-cryptoxanthin levels. CONCLUSION: These results have implications for the design of future epidemiologic studies focused on assessing RA-disease association and intervention studies aimed at modulating RA levels.

Dietary intake and risk of persistent human papillomavirus (HPV) infection: the Ludwig-McGill HPV Natural History Study.

The association between dietary intake and persistence of type-specific human papillomavirus (HPV) infection, during a 12-month period, among 433 women participating in the Ludwig-McGill HPV Natural History Study was evaluated by use of a nested case-control design. Dietary intake was assessed by a food-frequency questionnaire at the month-4 visit. HPV status was assessed at months 0, 4, 8, and 12 by polymerase chain reaction (MY09/11). Only women who ever tested positive for HPV were included in the present study: 248 had transient HPV infections (1 of 4 positive tests or nonconsecutively positive), and 185 had persistent HPV infections (> or =2 consecutive tests positive for the same HPV type). Risk of type-specific, persistent HPV infection was lower among women reporting intake values of beta-cryptoxanthin and lutein/zeaxanthin in the upper 2 quartiles and intake values of vitamin C in the upper quartile, compared with those reporting intake in the lowest quartile. Consumption of papaya > or =1 time/week was inversely associated with persistent HPV infection.