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C. E. Butterworth, Jr, MD; Kenneth D. Hatch, MD; Maurizio Macaluso, MD; Philip Cole, MD; Howerde E. Sauberlich, PhD; Seng-Jaw Soong, PhD; Matthew Borst, MD; Vicki V. Baker, MD

JAMA. 1992;267(4):528-533.

Abstract
Objective.
—To test the hypothesis that nutritional deficiency affects the incidence of cervical dysplasia in young women.

Design and Setting.
—Case-control study. Participants were derived from community family-planning clinics and referrals to a colposcopy center.

Participants.
—A total of 726 subjects were screened, yielding 294 cases of dysplasia and 170 controls defined by coexistent cytologic and colposcopic evidence.

Main Outcome Measures.
—Planned prior to data collection. Odds ratios were computed using logistic regression models to evaluate association between cervical dysplasia and sociodemographic, sexual, and reproductive factors; smoking; oral contraceptive use; human papillomavirus (HPV) infection; and 12 nutritional indices determined by blind analysis of nonfasting blood specimens.

Results.
—The number of sexual partners, parity, oral contraceptive use, and HPV-16 infection were significantly associated with cervical dysplasia. Plasma nutrient levels were generally not associated with risk. However, red blood cell folate levels at or below 660 nmol/L interacted with HPV-16 infection. The adjusted odds ratio for HPV-16 was 1.1 among women with folate levels above 660 nmol/L but 5.1 (95% confidence interval, 2.3 to 11) among women with lower levels. Interactions of red blood cell folate levels with cigarette smoking and parity were also present but were not statistically significant.

Conclusion.
—Low red blood cell folate levels enhance the effect of other risk factors for cervical dysplasia and, in particular, that of HPV-16 infection.

(JAMA. 1992;267:528-533)

Author Affiliations
From the Department of Nutrition Sciences, School of Medicine and School of Health Related Professions (Drs Butterworth and Sauberlich), the Department of Obstetrics and Gynecology, School of Medicine (Drs Hatch, Borst, and Baker), the Department of Epidemiology, School of Public Health (Drs Macaluso and Cole), and the Department of Biostatistics and Biomathematics, Comprehensive Cancer Center (Dr Soong), University of Alabama at Birmingham. Dr Hatch is now with the Department of Obstetrics and Gynecology, University of Arizona Health Sciences Center, Tucson. Dr Baker is now with the Department of Obstetrics and Gynecology, University of Cincinnati (Ohio) Medical Center.

Footnotes
Reprint requests to Department of Nutrition Sciences, University of Alabama at Birmingham, UAB Station, Birmingham, AL 35294-3360 (Dr Butterworth).

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