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) infectionsmoking and oral contraceptive use. The increased risks observed with exposure to either of these factors were similar and significant, about 4050 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 hypothesisthat 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 womenwere tested, on average, every 4 months. Infections of 12 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.
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