Influence of physiologic folate deficiency on human papillomavirus type 16 (HPV16)-harboring human keratinocytes in vitro and in vivo

Journal of Biological Chemistry

Volumn 287, Issue 15, 2012, Pages 12559-12577

  Xiao, Suhong ^a   Tang, Ying Sheng ^a   Khan, Rehana A ^a   Zhang, Yonghua ^a   Kusumanchi, Praveen ^a,c   Stabler, Sally P ^b   Jayaram, Hiremagalur N ^a,c   Antony, Asók C ^a,c  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^c RICHARD L ROUDEBUSH VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPITHELIAL TISSUE; GENOMIC DNA; HOMOCYSTEINES; HUMAN KERATINOCYTES; HUMAN PAPILLOMAVIRUS; IN-VITRO; KERATINOCYTES; MOLECULAR LINKAGES; NATURAL HISTORY; NUCLEAR RIBONUCLEOPROTEIN; ONCOGENIC TRANSFORMATION; POLYADENYLATION; POST-TRANSCRIPTIONAL; VIRAL LOAD; VIRAL PARTICLES;

DISEASES; DNA; GENES; HISTOLOGY; MONOLAYERS; NUTRITION; RNA; TISSUE;

PHYSIOLOGY;

CIS ACTING ELEMENT; GENOMIC DNA; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN E1; MESSENGER RNA; POLYURIDYLIC ACID; PROTEIN E6; PROTEIN E7; UNCLASSIFIED DRUG; VIRUS DNA; VIRUS RNA;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL IMMORTALIZATION; CONTROLLED STUDY; CYANOCOBALAMIN DEFICIENCY; DNA INTEGRATION; FOLIC ACID DEFICIENCY; HUMAN; HUMAN CELL; HUMAN PAPILLOMAVIRUS TYPE 16; IN VITRO STUDY; IN VIVO STUDY; KERATINOCYTE; MALIGNANT TRANSFORMATION; MONOLAYER CULTURE; MOUSE; NONHUMAN; OPERON; PAPILLOMAVIRUS INFECTION; POLYADENYLATION; PRIORITY JOURNAL; PROTEIN RNA BINDING; VIRUS CARCINOGENESIS; VIRUS LOAD; VIRUS PARTICLE;

ANIMALS; BASE SEQUENCE; CAPSID PROTEINS; CATALASE; CELL CULTURE TECHNIQUES; CELL PROLIFERATION; CELL TRANSFORMATION, VIRAL; CELLS, CULTURED; FEMALE; FOLIC ACID; FOLIC ACID DEFICIENCY; GENES, REPORTER; HETEROGENEOUS-NUCLEAR RIBONUCLEOPROTEINS; HOMOCYSTEINE; HOST-PATHOGEN INTERACTIONS; HUMAN PAPILLOMAVIRUS 16; HUMANS; KERATINOCYTES; MICE; MICE, NUDE; MOLECULAR SEQUENCE DATA; NEOPLASMS, EXPERIMENTAL; ONCOGENE PROTEINS, VIRAL; PAPILLOMAVIRUS INFECTIONS; PROTEIN BINDING; PROTEOLYSIS; RNA, MESSENGER; RNA, VIRAL; SULFHYDRYL COMPOUNDS; TUMOR BURDEN; VIRUS INTEGRATION;

HUMAN PAPILLOMAVIRUS TYPE 16; MUS;

EID: 84859480845     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M111.317040     Document Type: Article

References (81)

1. Flores, E. R., Allen-Hoffmann, B. L., Lee, D., and Lambert, P. F. (2000) The human papillomavirus type 16 E7 oncogene is required for the productive stage of the viral life cycle. J. Virol. 74, 6622-6631 (Pubitemid 30429831)
2. Bosch, F. X., Lorincz, A., Muñoz, N., Meijer, C. J., and Shah, K. V. (2002) The causal relation between human papillomavirus and cervical cancer. J. Clin. Path. 55, 244-265 (Pubitemid 34293391)
3. Laimins, L. A. (1993) The biology of human papillomaviruses. From warts to cancer. Infect. Agents Dis. 2, 74-86
4. Longworth, M. S., and Laimins, L. A. (2004) Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol. Mol. Biol. Rev. 68, 362-372 (Pubitemid 38756870)
5. Johnston, C. (2000) Quantitative tests for human papillomavirus. Lancet 355, 2179-2180
6. Schwartz, S. (2000) Regulation of human papillomavirus late gene expression. Upsala J. Med. Sci. 105, 171-192
7. Collier, B., Goobar-Larsson, L., Sokolowski, M., and Schwartz, S. (1998) Translational inhibition in vitro of human papillomavirus type 16 L2 mRNA mediated through interaction with heterogenous ribonucleoprotein K and poly(rC)-binding proteins 1 and 2. J. Biol. Chem. 273, 22648-22656 (Pubitemid 28399835)
8. Sun, X. L., and Antony, A. C. (1996) Evidence that a specific interaction between an 18-base cis-element in the 5′-untranslated region of human folate receptor-α mRNA and a 46-kDa cytosolic trans-factor is critical for translation. J. Biol. Chem. 271, 25539-25547
9. Xiao, X., Tang, Y. S., Mackins, J. Y., Sun, X. L., Jayaram, H. N., Hansen, D. K., and Antony, A. C. (2001) Isolation and characterization of a folate receptor mRNA-binding trans-factor from human placenta. Evidence favoring identity with heterogeneous nuclear ribonucleoprotein E1. J. Biol. Chem. 276, 41510-41517
10. Antony, A., Tang, Y. S., Khan, R. A., Biju, M. P., Xiao, X., Li, Q. J., Sun, X. L., Jayaram, H. N., and Stabler, S. P. (2004) Translational up-regulation of folate receptors is mediated by homocysteine via RNA-heterogeneous nuclear ribonucleoprotein E1 interactions. J. Clin. Invest. 113, 285-301 (Pubitemid 38544213)
11. Tang, Y. S., Khan, R. A., Zhang, Y., Xiao, S., Wang, M., Hansen, D. K., Jayaram, H. N., and Antony, A. C. (2011) Incrimination of heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) as a candidate sensor of physiological folate deficiency. J. Biol. Chem. 286, 39100-39115
12. Flores, E. R., Allen-Hoffmann, B. L., Lee, D., Sattler, C. A., and Lambert, P. F. (1999) Establishment of the human papillomavirus type 16 (HPV-16) life cycle in an immortalized human foreskin keratinocyte cell line. Virology 262, 344-354 (Pubitemid 29474297)
13. Zhao, X., Oberg, D., Rush, M., Fay, J., Lambkin, H., and Schwartz, S. (2005) A 57-nucleotide upstream early polyadenylation element in human papillomavirus type 16 interacts with hFip1, CstF-64, hnRNP C1/C2, and polypyrimidine tract binding protein. J. Virol. 79, 4270-4288 (Pubitemid 40388365)
14. Motulsky, H., and Christopoulos, A. (2004) Fitting Models to Biological Data using Linear and Nonlinear Regression., 1st Ed., pp. 296-338, Oxford University Press, New York
15. Shi, H., Bencze, K. Z., Stemmler, T. L., and Philpott, C. C. (2008) A cytosolic iron chaperone that delivers iron to ferritin. Science 320, 1207-1210 (Pubitemid 351929507)
16. Peitsaro, P., Johansson, B., and Syrjänen, S. (2002) Integrated human papillomavirus type 16 is frequently found in cervical cancer precursors as demonstrated by a novel quantitative real-time PCR technique. J. Clin. Microbiol. 40, 886-891 (Pubitemid 34208640)
17. Carcopino, X., Henry, M., Benmoura, D., Fallabregues, A. S., Richet, H., Boubli, L., and Tamalet, C. (2006) Determination of HPV type 16 and 18 viral load in cervical smears of women referred to colposcopy. J. Med. Virol. 78, 1131-1140
18. Brandsma, J. L., Brownstein, D. G., Xiao, W., and Longley, B. J. (1995) Papilloma formation in human foreskin xenografts after inoculation of human papillomavirus type 16 DNA. J. Virol. 69, 2716-2721
19. Bonnez, W. (2005) The HPV xenograft severe combined immunodeficiency mouse model. Methods Mol. Med. 119, 203-216
20. Feldman, J. P., Goldwasser, R., Mark, S., Schwartz, J., and Orion, I. (2009) A mathematical model for tumor volume evaluation using two-dimensions. J. Appl. Quant. Methods 4, 455-462
21. Büdy, B., O'Neill, R., DiBello, P. M., Sengupta, S., and Jacobsen, D. W. (2006) Homocysteine transport by human aortic endothelial cells. Identification and properties of import systems. Arch. Biochem. Biophys. 446, 119-130 (Pubitemid 43234223)
22. Yuspa, S. H., Kilkenny, A. E., Steinert, P. M., and Roop, D. R. (1989) Expression of murine epidermal differentiation markers is tightly regulated by restricted extracellular calcium concentrations in vitro. J. Cell Biol. 109, 1207-1217 (Pubitemid 19220102)
23. Xiao, S., Hansen, D. K., Horsley, E. T., Tang, Y. S., Khan, R. A., Stabler, S. P., Jayaram, H. N., and Antony, A. C. (2005) Maternal folate deficiency results in selective up-regulation of folate receptors and heterogeneous nuclear ribonucleoprotein-E1 associated with multiple subtle aberrations in fetal tissues. Birth Defects Res. A Clin. Mol. Teratol. 73, 6-28 (Pubitemid 40165269)
24. Kalantari, M., Karlsen, F., Kristensen, G., Holm, R., Hagmar, B., and Johansson, B. (1998) Disruption of the E1 and E2 reading frames of HPV 16 in cervical carcinoma is associated with poor prognosis. Int. J. Gynecol. Pathol. 17, 146-153 (Pubitemid 28151014)
25. Ostareck-Lederer, A., Ostareck, D. H., and Hentze, M. W. (1998) Cytoplasmic regulatory functions of the KH-domain proteins hnRNPs K and E1/E2. Trends Biochem. Sci 23, 409-411 (Pubitemid 28540737)
26. Wang, X., Kiledjian, M., Weiss, I. M., and Liebhaber, S. A. (1995) Detection and characterization of a 3′-untranslated region ribonucleoprotein complex associated with human α-globin mRNA stability. Mol. Cell Biol. 15, 1769-1777
27. Jiang, Y., Xu, X. S., and Russell, J. E. (2006) A nucleolin-binding 3′-untranslated region element stabilizes β-globin mRNA in vivo. Mol. Cell Biol. 26, 2419-2429 (Pubitemid 43346940)
28. Czyzyk-Krzeska, M. F., and Bendixen, A. C. (1999) Identification of the poly(C)-binding protein in the complex associated with the 3′-untranslated region of erythropoietin messenger RNA. Blood 93, 2111-2120 (Pubitemid 29128516)
29. Giles, K. M., Daly, J. M., Beveridge, D. J., Thomson, A. M., Voon, D. C., Furneaux, H. M., Jazayeri, J. A., and Leedman, P. J. (2003) The 3′-untranslated region of p21WAF1 mRNA is a composite cis-acting sequence bound by RNA-binding proteins from breast cancer cells, including HuR and poly(C)-binding protein. J. Biol. Chem. 278, 2937-2946 (Pubitemid 36801199)
30. Paulding, W. R., and Czyzyk-Krzeska, M. F. (1999) Regulation of tyrosine hydroxylase mRNA stability by protein-binding, pyrimidine-rich sequence in the 3′-untranslated region. J. Biol. Chem. 274, 2532-2538
31. Stefanovic, B., Hellerbrand, C., Holcik, M., Briendl, M., Liebhaber, S. A., and Brenner, D. A. (1997) Posttranscriptional regulation of collagen α1(I) mRNA in hepatic stellate cells. Mol. Cell Biol. 17, 5201-5209 (Pubitemid 27357619)
32. Yeap, B. B., Voon, D. C., Vivian, J. P., McCulloch, R. K., Thomson, A. M., Giles, K. M., Czyzyk-Krzeska, M. F., Furneaux, H., Wilce, M. C., Wilce, J. A., and Leedman, P. J. (2002) Novel binding of HuR and poly(C)-binding protein to a conserved UC-rich motif within the 3′-untranslated region of the androgen receptor messenger RNA. J. Biol. Chem. 277, 27183-27192 (Pubitemid 34951734)
33. Thyagarajan, A., and Szaro, B. G. (2004) Phylogenetically conserved binding of specific K homology domain proteins to the 3′-untranslated region of the vertebrate middle neurofilament mRNA. J. Biol. Chem. 279, 49680-49688 (Pubitemid 39577771)
34. Woolaway, K., Asai, K., Emili, A., and Cochrane, A. (2007) hnRNP E1 and E2 have distinct roles in modulating HIV-1 gene expression. Retrovirology 4, 28
35. Choi, Y. D., Grabowski, P. J., Sharp, P. A., and Dreyfuss, G. (1986) Heterogeneous nuclear ribonucleoproteins. Role in RNA splicing. Science 231, 1534-1539
36. Chaudhury, A., Chander, P., and Howe, P. H. (2010) Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes. Focus on hnRNP E1's multifunctional regulatory roles. RNA 16, 1449-1462
37. Das, K. C., and Herbert, V. (1989) In vitroDNAsynthesis by megaloblastic bone marrow. Effect of folates and cobalamins on thymidine incorporation and de novo thymidylate synthesis. Am. J. Hematol. 31, 11-20 (Pubitemid 19127425)
38. Wickramasinghe, S. N., and Fida, S. (1994) Bone marrow cells from vitamin B12- and folate-deficient patients misincorporate uracil into DNA. Blood 83, 1656-1661
39. Goulian, M., Bleile, B., and Tseng, B. Y. (1980) Methotrexate-induced misincorporation of uracil into DNA. Proc. Natl. Acad. Sci. U.S.A. 77, 1956-1960 (Pubitemid 10089583)
40. Goulian, M., Bleile, B., and Tseng, B. Y. (1980) The effect of methotrexate on levels of dUTP in animal cells. J. Biol. Chem. 255, 10630-10637 (Pubitemid 11171721)
41. Reidy, J. A. (1988) Role of deoxyuridine incorporation and DNA repair in the expression of human chromosomal fragile sites. Mutat. Res. 200, 215-220
42. Duthie, S. J., and Hawdon, A. (1998) DNA instability (strand breakage, uracil misincorporation, and defective repair) is increased by folic acid depletion in human lymphocytes in vitro. FASEB J. 12, 1491-1497 (Pubitemid 28506718)
43. Mashiyama, S. T., Courtemanche, C., Elson-Schwab, I., Crott, J., Lee, B. L., Ong, C. N., Fenech, M., and Ames, B. N. (2004) Uracil in DNA, determined by an improved assay, is increased when deoxynucleosides are added to folate-deficient cultured human lymphocytes. Anal. Biochem. 330, 58-69 (Pubitemid 38746975)
44. Barnes, D. E., and Lindahl, T. (2004) Repair and genetic consequences of endogenousDNAbase damage in mammalian cells. Annu. Rev. Genet. 38, 445-476 (Pubitemid 40013735)
45. Lindahl, T. (2000) Suppression of spontaneous mutagenesis in human cells by DNA base excision-repair. Mutat Res. 462, 129-135
46. Blount, B. C., Mack, M. M., Wehr, C. M., MacGregor, J. T., Hiatt, R. A., Wang, G., Wickramasinghe, S. N., Everson, R. B., and Ames, B. N. (1997) Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage. Implications for cancer and neuronal damage. Proc. Natl. Acad. Sci. U.S.A. 94, 3290-3295
47. Ciappio, E., and Mason, J. B. (2010) Folate and Carcinogenesis. Basic Mechanisms. in Folate in Health and Disease, 2nd Ed. (Bailey, L. B., ed) pp. 235-262, CRC Press, Inc., Boca Raton, FL
48. Ames, B. N., and Wakimoto, P. (2002) Are vitamin and mineral deficiencies a major cancer risk? Nat. Rev. Cancer 2, 694-704 (Pubitemid 37328920)
49. Dianov, G. L., Timchenko, T. V., Sinitsina, O. I., Kuzminov, A. V., Medvedev, O. A., and Salganik, R. I. (1991) Repair of uracil residues closely spaced on the opposite strands of plasmid DNA results in double-strand break and deletion formation. Mol. Gen. Genet. 225, 448-452
50. Kim, Y. I., Pogribny, I. P., Basnakian, A. G., Miller, J. W., Selhub, J., James, S. J., and Mason, J. B. (1997) Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p53 tumor suppressor gene. Am. J. Clin. Nutr. 65, 46-52 (Pubitemid 27020458)
51. Woodman, C. B., Collins, S. I., and Young, L. S. (2007) The natural history of cervical HPV infection. Unresolved issues. Nat. Rev. Cancer 7, 11-22 (Pubitemid 46020844)
52. Jeon, S., and Lambert, P. F. (1995) Integration of human papillomavirus type 16DNAinto the human genome leads to increased stability of E6 and E7 mRNAs. Implications for cervical carcinogenesis. Proc. Natl. Acad. Sci. U.S.A. 92, 1654-1658
53. Jeon, S., Allen-Hoffmann, B. L., and Lambert, P. F. (1995) Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J. Virol. 69, 2989-2997
54. Wilke, C. M., Hall, B. K., Hoge, A., Paradee, W., Smith, D. I., and Glover, T. W. (1996) FRA3B extends over a broad region and contains a spontaneous HPV16 integration site. Direct evidence for the coincidence of viral integration sites and fragile sites. Hum. Mol. Genet. 5, 187-195 (Pubitemid 26036914)
55. Thorland, E. C., Myers, S. L., Persing, D. H., Sarkar, G., McGovern, R. M., Gostout, B. S., and Smith, D. I. (2000) Human papillomavirus type 16 integrations in cervical tumors frequently occur in common fragile sites. Cancer Res. 60, 5916-5921
56. Thorland, E. C., Myers, S. L., Gostout, B. S., and Smith, D. I. (2003) Common fragile sites are preferential targets for HPV16 integrations in cervical tumors. Oncogene 22, 1225-1237 (Pubitemid 36363386)
57. Sutherland, G. R., and Richards, R. I. (1995) The molecular basis of fragile sites in human chromosomes. Curr. Opin. Genet. Dev. 5, 323-327
58. Savelyeva, L., Sagulenko, E., Schmitt, J. G., and Schwab, M. (2006) Lowfrequency common fragile sites. Link to neuropsychiatric disorders? Cancer Lett. 232, 58-69 (Pubitemid 43054978)
59. Schwartz, M., Zlotorynski, E., and Kerem, B. (2006) The molecular basis of common and rare fragile sites. Cancer Lett. 232, 13-26 (Pubitemid 43054977)
60. Barbi, G., Steinbach, P., and Vogel, W. (1984) Nonrandom distribution of methotrexate-induced aberrations on human chromosomes. Detection of further folic acid-sensitive fragile sites. Hum. Genet. 68, 290-294 (Pubitemid 15179280)
61. Glover, T. W., Berger, C., Coyle, J., and Echo, B. (1984) DNA polymerase α inhibition by aphidicolin induces gaps and breaks at common fragile sites in human chromosomes. Hum. Genet. 67, 136-142 (Pubitemid 14095149)
62. Yunis, J. J., and Soreng, A. L. (1984) Constitutive fragile sites and cancer. Science 226, 1199-1204 (Pubitemid 15221736)
63. Antony, A. C. (2009) Megaloblastic Anemias. in Hematology: Basic Principles and Practice, 5th Ed. (Hoffman, R., Benz, E. J., Jr., Shattil, S. J., Furie, B., Silberstein, L. E., McGlave, P., and Heslop, H., eds) pp. 491-524, Churchill Livingstone-Elsevier, Philadelphia
64. Keene, J. D. (2007) RNA regulons. Coordination of post-transcriptional events. Nat. Rev. Genet. 8, 533-543
65. White, W. I., Wilson, S. D., Bonnez, W., Rose, R. C., Koenig, S., and Suzich, J. A. (1998) In vitro infection and type-restricted antibody-mediated neutralization of authentic human papillomavirus type 16. J. Virol. 72, 959-964 (Pubitemid 28116873)
66. Campos, S. K., and Ozbun, M. A. (2009) Two highly conserved cysteine residues in HPV16 L2 form an intramolecular disulfide bond and are critical for infectivity in human keratinocytes. PLoS One 4, e4463
67. Gamarnik, A. V., and Andino, R. (1997) Two functional complexes formed by KH domain containing proteins with the 5′ noncoding region of poliovirus RNA. RNA 3, 882-892
68. Blyn, L. B., Towner, J. S., Semler, B. L., and Ehrenfeld, E. (1997) Requirement of poly(rC) binding protein 2 for translation of poliovirus RNA. J. Virol. 71, 6243-6246 (Pubitemid 27304973)
69. Chakravarty, I., and Sinha, R. (2002) Prevalence of micronutrient deficiency based on results obtained from the national pilot program on control of micronutrient malnutrition. Nutr. Rev. 60, S53-S58 (Pubitemid 34525592)
70. Antony, A. C. (2003) Vegetarianism and vitamin B-12 (cobalamin) deficiency. Am. J. Clin. Nutr. 78, 3-6
71. Chitambar, C. R., and Antony, A. C. (2006) Nutritional Aspects of Hematologic Diseases. in Modern Nutrition in Health and Disease, 10th Ed. (Shils, M. E., Shike, M., Ross, A. C., Caballero, B., and Cousins, R. J., eds) pp. 1436-1461, Lippicott Williams & Wilkins, Baltimore
72. Antony, A. C. (2001) Prevalence of cobalamin (vitamin B-12) and folate deficiency in India. Audi alteram partem. Am. J. Clin. Nutr. 74, 157-159
73. Stabler, S. P., and Allen, R. H. (2004) Vitamin B12 deficiency as a worldwide problem. Annu. Rev. Nutr. 24, 299-326 (Pubitemid 38938794)
74. Butterworth, C. E., Jr., Hatch, K. D., Gore, H., Mueller, H., and Krumdieck, C. L. (1982) Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am. J. Clin. Nutr. 35, 73-82 (Pubitemid 12126589)
75. Butterworth, C. E., Jr., Hatch, K. D., Macaluso, M., Cole, P., Sauberlich, H. E., Soong, S. J., Borst, M., and Baker, V. V. (1992) Folate deficiency and cervical dysplasia. JAMA 267, 528-533
76. Weinstein, S. J., Ziegler, R. G., Selhub, J., Fears, T. R., Strickler, H. D., Brinton, L. A., Hamman, R. F., Levine, R. S., Mallin, K., and Stolley, P. D. (2001) Elevated serum homocysteine levels and increased risk of invasive cervical cancer in US women. Cancer Causes Control 12, 317-324 (Pubitemid 32553624)
77. Thomson, S. W., Heimburger, D. C., Cornwell, P. E., Turner, M. E., Sauberlich, H. E., Fox, L. M., and Butterworth, C. E. (2000) Effect of total plasma homocysteine on cervical dysplasia risk. Nutr. Cancer 37, 128-133
78. Butterworth, C. E., Jr. (1993) Folate status, women's health, pregnancy outcome, and cancer. J. Am. Coll. Nutr. 12, 438-441
79. Kwanbunjan, K., Saengkar, P., Cheeramakara, C., Thanomsak, W., Benjachai, W., Laisupasin, P., Buchachart, K., Songmuaeng, K., and Boontaveeyuwat, N. (2005) Low folate status as a risk factor for cervical dysplasia in Thai women. Nutr. Res. 25, 641-654 (Pubitemid 41262159)
80. Piyathilake, C. J., Badiga, S., Paul, P., Vijayaraghavan, K., Vedantham, H., Sudula, M., Sowjanya, P., Ramakrishna, G., Shah, K. V., Partridge, E. E., and Gravitt, P. E. (2010) Indian women with higher serum concentrations of folate and vitamin B12 are significantly less likely to be infected with carcinogenic or high-risk (HR) types of human papillomaviruses (HPVs). Int. J. Womens Health 2, 7-12
81. Piyathilake, C. J., Henao, O. L., Macaluso, M., Cornwell, P. E., Meleth, S., Heimburger, D. C., and Partridge, E. E. (2004) Folate is associated with the natural history of high-risk human papillomaviruses. Cancer Res. 64, 8788-8793 (Pubitemid 39552099)