VOL. 2, No. 3, July 2005

C. J. Piyathilake [2005] Med Hypotheses Res 2: 503-513.

Micronutrients and Cervical Neoplasia ― Recent
Advances in Risk Assessment

Chandrika J. Piyathilake*

Department of Nutrition Sciences of the University of Alabama at Birmingham,
Birmingham, Alabama, USA

Abstract. This manuscript reviews the current state of knowledge of cervical
carcinogenesis and present recent results on the relationships among micronutrients and
natural history of HR-HPVs, genetic polymorphisms and cervical intraepithelial neoplasia
(CIN). Numerous studies have attempted to determine associations between micronutrients
and risk of CIN and cervical cancer. Studies conducted before a reliable test for assessing
HPV infections was available may have resulted in misclassification due to differences in
assay sensitivity leading potentially to residual confounding. Another limitation in previous
studies may be related to methodological limitations such as the proper choice of controls
for case-control studies. Since cervical cancer does not develop in the absence of HR-HPV
infections, only controls exposed to HR-HPV should ideally be included in studies that
investigate co-factors for CIN or cervical cancer. Also, the recruitment of subjects for these
studies had been based on screening programs that used different approaches such as
cytology, colposcopic impression or biopsy to identify pre-neoplastic cervical lesions. Recent
studies have clearly demonstrated that some of these approaches could lead to substantial
under detection and misclassification of preneoplastic lesions of the cervix. Recent studies
that addressed these issues have demonstrated that folate is an important micronutrient in
cervical cancer prevention via its influence on HR-HPV. Future studies are warranted to
assess whether folate-related biomarkers may be used to identify subjects who are at risk of
developing cervical cancer. Further studies are also needed to systematically evaluate the
interactions between folate and other micronutrients and polymorphisms in the folate
metabolic pathway enzymes.

*Address all correspondence to: Dr. Chandrika J. Piyathilake, Department of Nutrition
Sciences, Division of Nutritional Biochemistry and Molecular Biology, University of
Alabama at Birmingham, Webb 318A, Birmingham, AL 35294, USA.
Telephone: 205-975-5398. Fax: 205-966-2859. E-Mail:

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