Cancer Causes & Control

, Volume 21, Issue 1, pp 51–59 | Cite as

The association between fruit and vegetable consumption and HPV viral load in high-risk HPV-positive women with cervical intraepithelial neoplasia

  • Jong Ha Hwang
  • Jae Kwan Lee
  • Tae Jin Kim
  • Mi Kyung Kim
Original paper


We evaluated the relationship between the dietary intake of vegetables and fruits, and the risk of cervical intraepithelial neoplasia (CIN) and determined whether these associations were modified by human papillomavirus (HPV) viral load. We enrolled 1,096 women aged 18–65 to participate in a HPV cohort study from March 2006 up to present. For this analysis, we included 328 HPV-positive women (166 controls, 90 CIN I and 72 CIN II/III). The multivariate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated by multinomial logistic methods. After controlling for potential confounders, we found that a higher HPV viral load was associated with an increased risk of CIN I (OR = 2.68, 95% CI, 1.19–6.04) and CIN II/III (OR = 2.78, 95% CI, 1.15–6.72). The relationships between HPV infection, dietary intake of vegetables and fruits and risk of CIN were not statistically significant. However, subjects with lower intake of vegetables and fruits, and a higher viral load (≥15.5) have a higher risk of CIN II/III (OR = 2.84(1.26–6.42), interaction p = 0.06 for vegetables; OR = 2.93(1.25–6.87), interaction p = 0.01 for fruits), compared with subjects with lower intake of vegetables and fruits, and a lower viral load (<15.5). Our findings suggest that the dietary intake of vegetables and fruits is associated with the progression of cervical carcinogenesis.


HPV Viral load Vegetable Fruit Cervical dysplasia 



This work was supported by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (R01-2006-000-10621-0).


  1. 1.
    Parkin DM, Bray FI, Devesa SS (2001) Cancer burden in the year 2000. The global picture. Eur J Cancer 37(Suppl 8):S4–S66CrossRefPubMedGoogle Scholar
  2. 2.
    Schiffman MH, Brinton LA (1995) The epidemiology of cervical carcinogenesis. Cancer 76(10 Suppl):1888–1901CrossRefPubMedGoogle Scholar
  3. 3.
    Moscicki AB, Schiffman M, Kjaer S, Villa LL (2006) Chapter 5: updating the natural history of HPV and anogenital cancer. Vaccine 24(Suppl 3):S3/42–S3/51Google Scholar
  4. 4.
    Castellsague X, Munoz N (2003) Chapter 3: cofactors in human papillomavirus carcinogenesis–role of parity, oral contraceptives, and tobacco smoking. J Natl Cancer Inst Monogr 31:20–28PubMedGoogle Scholar
  5. 5.
    Wang SS, Hildesheim A (2003) Chapter 5: viral and host factors in human papillomavirus persistence and progression. J Natl Cancer Inst Monogr 31:35–40PubMedGoogle Scholar
  6. 6.
    Castle PE, Giuliano AR (2003) Chapter 4: genital tract infections, cervical inflammation, and antioxidant nutrients–assessing their roles as human papillomavirus cofactors. J Natl Cancer Inst Monogr 31:29–34PubMedGoogle Scholar
  7. 7.
    Romney SL, Ho GYF, Palan PR et al (1997) Effects of β-carotene and other factors on outcome of cervical dysplasia and human papillomavirus infection. Gynecol Oncol 65:483–492CrossRefPubMedGoogle Scholar
  8. 8.
    Mackerras D, Irwig L, Simpson JM et al (1999) Randomized double-blind tiral of beta-carotene and vitamin C in women with minor cervical abnormalities. Br J Cancer 79:1448–1453CrossRefPubMedGoogle Scholar
  9. 9.
    de Vet HC, Knipschild PG, Grol ME, Schouten HJ, Sturmans F (1991) The role of beta-carotene and other dietary factors in the aetiology of cervical dysplasia: results of a case–control study. Int J Epidemiol 20(3):603–610CrossRefPubMedGoogle Scholar
  10. 10.
    Ho GY, Burk RD, Klein S et al (1995) Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia. J Natl Cancer Inst 87(18):1365–1371CrossRefPubMedGoogle Scholar
  11. 11.
    Nagata C, Shimizu H, Yoshikawa H et al (1999) Serum carotenoids and vitamins and risk of cervical dysplasia from a case–control study in Japan. Br J Cancer 81(7):1234–1237CrossRefPubMedGoogle Scholar
  12. 12.
    Hernandez-Hernandez DM, Ornelas-Bernal L, Guido-Jimenez M et al (2003) Association between high-risk human papillomavirus DNA load and precursor lesions of cervical cancer in Mexican women. Gynecol Oncol 90(2):310–317CrossRefPubMedGoogle Scholar
  13. 13.
    Ylitalo N, Sorensen P, Josefsson AM et al (2000) Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ: a nested case–control study. Lancet 355(9222):2194–2198CrossRefPubMedGoogle Scholar
  14. 14.
    Beskow AH, Gyllensten UB (2002) Host genetic control of HPV 16 titer in carcinoma in situ of the cervix uteri. Int J Cancer 101(6):526–531CrossRefPubMedGoogle Scholar
  15. 15.
    van Duin M, Snijders PJ, Schrijnemakers HF et al (2002) Human papillomavirus 16 load in normal and abnormal cervical scrapes: an indicator of CIN II/III and viral clearance. Int J Cancer 98(4):590–595CrossRefPubMedGoogle Scholar
  16. 16.
    Sun CA, Lai HC, Chang CC, Neih S, Yu CP, Chu TY (2001) The significance of human papillomavirus viral load in prediction of histologic severity and size of squamous intraepithelial lesions of uterine cervix. Gynecol Oncol 83(1):95–99CrossRefPubMedGoogle Scholar
  17. 17.
    Kim YM, Park JY, Lee KM et al (2008) Does pretreatment HPV viral load correlate with prognosis in patients with early stage cervical carcinoma? J Gynecol Oncol 19(2):113–116CrossRefPubMedGoogle Scholar
  18. 18.
    Solomon D, Davey D, Kurman R et al (2002) The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 287(16):2114–2119CrossRefPubMedGoogle Scholar
  19. 19.
    Kulmala SM, Syrjanen S, Shabalova I et al (2004) Human papillomavirus testing with the hybrid capture 2 assay and PCR as screening tools. J Clin Microbiol 42(6):2470–2475CrossRefPubMedGoogle Scholar
  20. 20.
    Kim YO, Kim MK, Lee SA, Yoon YM, Sasaki S (2009) A study testing the usefulness of a dish-based food-frequency questionnaire developed for epidemiological studies in Korea. Br J Nutr 101(8):1218–1227CrossRefPubMedGoogle Scholar
  21. 21.
    Korea Health Industry Development Institute, Ministry of Health and Welfare (ed) (2000) Development of nutrient database, recipe, and portion size [Korean]. Korea Health Industry Development Institute, Ministry of Health and Welfare, SeoulGoogle Scholar
  22. 22.
    Cadenas E, Packer L (1996) Handbook of antioxidants. M. Dekker, New YorkGoogle Scholar
  23. 23.
    Kritchevsky D, Bonfield C (1995) Dietary fiber in health & disease. Eagan Press, St. Paul, MinnGoogle Scholar
  24. 24.
    Verreault R, Chu J, Mandelson M, Shy K (1989) A case–control study of diet and invasive cervical cancer. Int J Cancer 43(6):1050–1054CrossRefPubMedGoogle Scholar
  25. 25.
    Ziegler RG, Jones CJ, Brinton LA et al (1991) Diet and the risk of in situ cervical cancer among white women in the United States. Cancer Causes Control 2(1):17–29CrossRefPubMedGoogle Scholar
  26. 26.
    Brock KE, Berry G, Mock PA, MacLennan R, Truswell AS, Brinton LA (1988) Nutrients in diet and plasma and risk of in situ cervical cancer. J Natl Cancer Inst 80(8):580–585CrossRefPubMedGoogle Scholar
  27. 27.
    Herrero R, Potischman N, Brinton LA et al (1991) A case–control study of nutrient status and invasive cervical cancer. I. Dietary indicators. Am J Epidemiol 134(11):1335–1346PubMedGoogle Scholar
  28. 28.
    Kwasniewska A, Charzewska J, Tukendorf A, Semczuk M (1998) Dietary factors in women with dysplasia colli uteri associated with human papillomavirus infection. Nutr Cancer 30(1):39–45CrossRefPubMedGoogle Scholar
  29. 29.
    Ziegler RG, Brinton LA, Hamman RF et al (1990) Diet and the risk of invasive cervical cancer among white women in the United States. Am J Epidemiol 132(3):432–445PubMedGoogle Scholar
  30. 30.
    La Vecchia C, Franceschi S, Decarli A et al (1984) Dietary vitamin A and the risk of invasive cervical cancer. Int J Cancer 34(3):319–322CrossRefPubMedGoogle Scholar
  31. 31.
    La Vecchia C, Decarli A, Fasoli M et al (1988) Dietary vitamin A and the risk of intraepithelial and invasive cervical neoplasia. Gynecol Oncol 30(2):187–195CrossRefPubMedGoogle Scholar
  32. 32.
    Marshall JR, Graham S, Byers T, Swanson M, Brasure J (1983) Diet and smoking in the epidemiology of cancer of the cervix. J Natl Cancer Inst 70(5):847–851PubMedGoogle Scholar
  33. 33.
    Shannon J, Thomas DB, Ray RM et al (2002) Dietary risk factors for invasive and in situ cervical carcinomas in Bangkok, Thailand. Cancer Causes Control 13(8):691–699CrossRefPubMedGoogle Scholar
  34. 34.
    Giuliano AR, Siegel EM, Roe DJ et al (2003) Dietary intake and risk of persistent human papillomavirus (HPV) infection: the Ludwig-McGill HPV natural history study. J Infect Dis 188(10):1508–1516CrossRefPubMedGoogle Scholar
  35. 35.
    Abba MC, Mouron SA, Gomez MA, Dulout FN, Golijow CD (2003) Association of human papillomavirus viral load with HPV16 and high-grade intraepithelial lesion. Int J Gynecol Cancer 13(2):154–158CrossRefPubMedGoogle Scholar
  36. 36.
    Schlecht NF, Trevisan A, Duarte-Franco E et al (2003) Viral load as a predictor of the risk of cervical intraepithelial neoplasia. Int J Cancer 103(4):519–524CrossRefPubMedGoogle Scholar
  37. 37.
    Flores R, Papenfuss M, Klimecki WT, Giuliano AR (2006) Cross-sectional analysis of oncogenic HPV viral load and cervical intraepithelial neoplasia. Int J Cancer 118(5):1187–1193CrossRefPubMedGoogle Scholar
  38. 38.
    Sun CA, Liu JF, Wu DM, Nieh S, Yu CP, Chu TY (2002) Viral load of high-risk human papillomavirus in cervical squamous intraepithelial lesions. Int J Gynaecol Obstet 76(1):41–47CrossRefPubMedGoogle Scholar
  39. 39.
    Castle PE, Schiffman M, Wheeler CM (2004) Hybrid capture 2 viral load and the 2-year cumulative risk of cervical intraepithelial neoplasia grade 3 or cancer. Am J Obstet Gynecol 191(5):1590–1597CrossRefPubMedGoogle Scholar
  40. 40.
    Castle PE, Schiffman M, Scott DR et al (2005) Semiquantitative human papillomavirus type 16 viral load and the prospective risk of cervical precancer and cancer. Cancer Epidemiol Biomarkers Prev 14(5):1311–1314CrossRefPubMedGoogle Scholar
  41. 41.
    Sherman ME, Wang SS, Wheeler CM et al (2003) Determinants of human papillomavirus load among women with histological cervical intraepithelial neoplasia 3: dominant impact of surrounding low-grade lesions. Cancer Epidemiol Biomarkers Prev 12(10):1038–1044PubMedGoogle Scholar
  42. 42.
    Lorincz AT, Castle PE, Sherman ME et al (2002) Viral load of human papillomavirus and risk of CIN3 or cervical cancer. Lancet 360(9328):228–229CrossRefPubMedGoogle Scholar
  43. 43.
    Hernandez BY, McDuffie K, Wilkens LR, Kamemoto L, Goodman MT (2003) Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12. Cancer Causes Control 14(9):859–870CrossRefPubMedGoogle Scholar
  44. 44.
    Conner EM, Grisham MB (1996) Inflammation, free radicals, and antioxidants. Nutrition 12(4):274–277CrossRefPubMedGoogle Scholar
  45. 45.
    Palmer HJ, Paulson KE (1997) Reactive oxygen species and antioxidants in signal transduction and gene expression. Nutr Rev 55(10):353–361PubMedCrossRefGoogle Scholar
  46. 46.
    Rosl F, Schwarz E (1997) Regulation of E6 and E7 oncogenic transcription. In: Tommasino M (ed) Papillomaviruses in human cancer: the roll of E6 and E7 oncoproteins. Landes Bioscience; Chapman & Hall, Austin, TX; New York, pp 25–70Google Scholar
  47. 47.
    Meydani SN, Wu D, Santos MS, Hayek MG (1995) Antioxidants and immune response in aged persons: overview of present evidence. Am J Clin Nutr 62(6 Suppl):1462S–1476SPubMedGoogle Scholar
  48. 48.
    Anderson R, Theron AJ (1990) Physiological potential of ascorbate, beta-carotene and alpha-tocopherol individually and in combination in the prevention of tissue damage, carcinogenesis and immune dysfunction mediated by phagocyte-derived reactive oxidants. World Rev Nutr Diet 62:27–58PubMedGoogle Scholar
  49. 49.
    Khare S, Tang SC, Pater M, Pater A (1996) Cofactors with HPV infections and oncogenesis. In: Lacey C (ed) Papillomavirus reviews: current research on papillomaviruses. Leeds Medical Information, Leeds, pp 55–60Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Jong Ha Hwang
    • 1
  • Jae Kwan Lee
    • 1
  • Tae Jin Kim
    • 2
  • Mi Kyung Kim
    • 3
  1. 1.Department of Obstetrics and GynecologyKorea University Guro Hospital, Korea University College of MedicineSeoulKorea
  2. 2.Department of Obstetrics and Gynecology, Cheil General Hospital & Women Health Center, College of MedicineKwandong UniversitySeoulKorea
  3. 3.Cancer Epidemiology BranchNational Cancer CenterGoyang-siKorea

Personalised recommendations