Am J Epidemiol 2003; 158:927-928.
Copyright © 2003 by Johns
Hopkins Bloomberg School of Public Health
LETTERS TO THE EDITOR |
TWO AUTHORS REPLY
Department of Epidemiology, University of Washington, Seattle, WA 98103
We appreciate Dr. Hendricks’ comments (1) on our paper (2). The potential mechanisms by which smoking and oral contraceptive use may modify either the risk of human papillomavirus (HPV) acquisition or progression to cervical neoplasia are not well understood, and additional research in this area is warranted.
The hypothesis offered by Dr. Hendricks (1)—that smoking or oral contraceptive use may affect HPV infection status by depleting levels of either folate or vitamin B12—is an interesting one, and epidemiologic studies that have explored this issue have produced mixed results. Dr. Hendricks cites studies that support the hypotheses that smoking and oral contraceptive use adversely affect folate and/or vitamin B12 and that depleted levels of these nutrients increase the risk of persistent HPV infection or cervical neoplasia. Other studies, however, have reported conflicting results. A study conducted among adolescent females in Canada reported no association between either smoking or oral contraceptive use and lower serum or red blood cell folate levels after controlling for folate intake, nor was smoking associated with lower serum B12 levels (3). Other studies have also reported no association between oral contraceptive use and levels of folate (4, 5). Furthermore, the majority of case-control studies of folate/vitamin B12 and cervical neoplasia have failed to find any association (6), and results from clinical intervention trials of folic acid do not suggest that folic acid supplementation alters the natural history of HPV infection (7, 8). Dr. Hendricks suggests that perhaps the associations between these nutrients and cervical cancer are early rather than late, citing a study that found an association between low vitamin B12 levels and persistent HPV infection (9). This study reported no association between folate and HPV persistence, however, and the same researchers also failed to find an association between either folate or vitamin B12 and HPV persistence among a smaller cohort of Hispanic women (6). Furthermore, if smoking- or oral-contraceptive-related folate/vitamin B12 depletion does adversely affect HPV infection status, we might expect to see a more consistent relation between smoking/oral contraceptive use and HPV infection in the literature; in contrast, the majority of studies have reported null associations (reviewed in our paper (2)).
While we do have banked serum from women enrolled in this study, there is some evidence to suggest that serum B12 radioimmunoassays may give falsely low results in oral contraceptive users (10) and that folate can be more accurately measured in red blood cells than in serum.
REFERENCES
- Hendricks KA. Re: "Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students." (Letter). Am J Epidemiol 2003;158:927.
[Free Full Text] - Winer RL, Lee SK, Hughes JP, et al. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol 2003;157:218–26.
[Abstract/Free Full Text] - Green TJ, Houghton LA, Donovan U, et al. Oral contraceptives did not affect biochemical folate indexes and homocysteine concentrations in adolescent females. J Am Diet Assoc 1998;98:49–55.[CrossRef][ISI][Medline]
- Steegers-Theunissen RP, Van Rossum JM, Steegers EA, et al. Sub-50 oral contraceptives affect folate kinetics. Gynecol Obstet Invest 1993;36:230–3.[ISI][Medline]
- Mooij PN, Thomas CM, Doesburg WH, et al. Multivitamin supplementation in oral contraceptive users. Contraception 1991;44:277–88.[CrossRef][ISI][Medline]
- Sedjo RL, Fowlers BM, Schneider A, et al. Folate, vitamin B12, and homocysteine status: findings of no relation between human papillomavirus persistence and cervical dysplasia. Nutrition 2003;19:497–502.[CrossRef][ISI][Medline]
- Childers JM, Chu J, Voigt LF, et al. Chemoprevention of cervical cancer with folic acid: a phase III Southwest Oncology Group Intergroup study. Cancer Epidemiol Biomarkers Prev 1995;4:155–9.[Abstract]
- Butterworth CEJ, Hatch K, Soong SJ, et al. Oral folic acid supplementation for cervical dysplasia: a clinical intervention trial. Am J Obstet Gynecol 1992;166:803–9.[ISI][Medline]
- Sedjo RL, Inserra P, Abrahamsen M, et al. Human papillomavirus persistence and nutrients involved in the methylation pathway among a cohort of young women. Cancer Epidemiol Biomarkers Prev 2002;11:353–9.
[Abstract/Free Full Text] - Gardyn J, Mittelman M, Zlotnik J, et al. Oral contraceptives can cause falsely low vitamin B(12) levels. Acta Haematol 2000;104:22–4.[CrossRef][ISI][Medline]
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  L. A. Koutsky and R. L. Winer TWO AUTHORS REPLY Am. J. Epidemiol., November 1, 2003; 158(9): 927 - 928. [Full Text] [PDF]
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