RE: GENITAL HUMAN PAPILLOMAVIRUS INFECTION: INCIDENCE AND RISK FACTORS IN A COHORT OF FEMALE UNIVERSITY STUDENTS

Katherine A. Hendricks

Science Department, The Medical Institute for Sexual Health, Austin, TX 78746

In the recent, excellent Journal article entitled, "Genital Human Papillomavirus Infection: Incidence and Risk Factors in a Cohort of Female University Students," the authors (1) identified and puzzled over two risk factors for human papillomavirus (HPV) infection—smoking and oral contraceptive use. The increased risks observed with exposure to either of these factors were similar and significant, about 40–50 percent over baseline. For each, the authors concluded that perhaps the risk factor was linked to some behaviors for which they had inadequately controlled.

I would like to offer an alternative hypothesis—that smoking and oral contraceptive use adversely affect levels of either folate or vitamin B12 and that the resulting "mal" nutrition adversely affects HPV infection status (e.g., immune response/clearance). A number of pieces of evidence make this idea viable. Both contraceptive use (24) and smoking (57) may adversely affect levels of folate and/or vitamin B12. Furthermore, a deficiency of either vitamin can result in elevated homocysteine levels. Both low folate (8) and elevated homocysteine (9) have been hypothesized to be risk factors for cervical intraepithelial neoplasia or cervical cancer.

Although some attention (i.e., case-control studies of cancer patients) has been paid to the hypothesis that elevated homocysteine levels or decreased folate levels (and consequently decreased levels of the universal methyl donor, S-adenosylmethionine) may be risk factors for cervical cancer, perhaps the associations are early rather than late. Could decreased folate or vitamin B12 levels (as might occur secondary to oral contraceptive use or smoking) be risk factors for HPV persistence? A few studies suggest this as a possibility. A study of university women using oral contraceptives found those whose folate levels were low to be at risk for a positive viraPap (HPV DNA dot-blot assay) result (10). A more recent study suggested that low vitamin B12 levels may be associated with persistent HPV infection (11). Recall that the young women in the study at issue (1)—the cohort study of university women—were tested, on average, every 4 months. Infections of 1–2 months’ duration could more easily have been missed.

This question could be addressed rather easily if the authors (1) have banked serum; testing serum vitamin B12 and folate levels is fairly inexpensive.

REFERENCES

  1. 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]
  2. Sutterlin MW, Bussen SS, Rieger L, et al. Serum folate and vitamin B12 levels in women using modern oral contraceptives (OC) containing 20 µg ethinyl estradiol. Eur J Obstet Gynecol Reprod Biol 2003;107:57–61.[CrossRef][ISI][Medline]
  3. Hjelt K, Brynskov J, Hippe E, et al. Oral contraceptives and the cobalamin (vitamin B12) metabolism. Acta Obstet Gynecol Scand 1985;64:59–63.[ISI][Medline]
  4. Hettiarachchy NS, Sri Kantha SS, Corea SM. The effect of oral contraceptive therapy and of pregnancy on serum folate levels of rural Sri Lankan women. Br J Nutr 1983;50:495–501.[ISI][Medline]
  5. Cafolla A, Dragoni F, Girelli G, et al. Folate status in Italian blood donors: relation to gender and smoking. Heamatologica 2000;85:694–8.
  6. McDonald SD, Perkins SL, Jodouin CA, et al. Folate levels in pregnant women who smoke: an important gene/environment interaction. Am J Obstet Gynecol 2002;187:620–5.[CrossRef][ISI][Medline]
  7. van Wersch JW, Janssens Y, Zandvoort JA. Folic acid, vitamin B(12), and homocysteine in smoking and non-smoking pregnant women. Eur J Obstet Gynecol Reprod Biol 2002;103:18–21.[CrossRef][ISI][Medline]
  8. Kwasniewska A, Tukendorf A, Semczuk M. Folate deficiency and cervical intraepithelial neoplasia. Eur J Gynaecol Oncol 1997;18:526–30.[ISI][Medline]
  9. Weinstein SJ, Ziegler RG, Selhub J, et al. Elevated serum homocysteine levels and increased risk of invasive cervical cancer in US women. Cancer Causes Control 2001;12:317–24.[CrossRef][ISI][Medline]
  10. Harper JM, Levine AJ Rosenthal DL, et al. Erythrocyte folate levels, oral contraceptive use and abnormal cervical cytology. Acta Cytol 1994;38:324–30.[ISI][Medline]
  11. 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]




This Article
Extract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (1)
Disclaimer
Request Permissions
Google Scholar
Articles by Hendricks, K. A.
PubMed
PubMed Citation
Articles by Hendricks, K. A.