Danielle Luciano, MD

Human Papillomavirus has emerged as a distinct cause of cervical  changes in young women. Its prevalence is continuously growing and is  considered at epidemic proportions with 20 million Americans already  infected and 5.5 million new cases reported annually. (2) (Center for  Disease Control and Prevention, Tracking the Hidden Epidemics., Trends  in STDs in the U.S. 2000, Atlanta, Georgia, 2000)

There are known risk factors associated with HPV cervical changes and  cervical cancer. These known risk factors are the number of one’s  sexual partners, age at first coitus, smoking and use of oral  contraception.

The objective of this study was to investigate the relationship  between known risk factors and unknown risk factors, such as nutrition,  vitamin deficiency and other lifestyle variables (i.e., drug/alcohol  use, exercise and sleep habits), on HPV cervical changes.

The results of this study may increase awareness for the general  public, influence behavior and aid in the prevention of the disease in  young women. New streams of clinical information may prevent the  progression of the disease to cancer in women who are already infected,  as HPV has been implicated in the pathogenesis of cervical cancer, the  number one gynecologic cancer in the world.

This two-arm study was performed between 2002 and 2004 in Lenox Hill  Hospital’s ambulatory clinic and physicians’ offices in New York City.  Approval was granted by the hospital’s Institutional Review Board. Each  woman gave written informed consent prior to participation.

A questionnaire to determine lifestyle and nutritional habits was  distributed to female volunteers between the ages of 18 and 35 (part 1  of the study). A previous pap smear was a requirement for participation.  However, whether the results of the pap smear were normal or abnormal  was not a consideration for recruitment.

Blood serum levels of vitamins C, E, and beta carotene were obtained  for part 2 of the study, and processed by Quest Laboratory. These  vitamins were selected for testing because an increased number of  reports had suggested that these antioxidants may act to prevent the  development of various malignancies (13).

Statistical analysis included Chi-Square, ANOVA, a Student T-test and 2x2 table to identify association between study variables.

One hundred sixty-four (164) women participated in the study. One  hundred (61%) of the participants had abnormal pap smear results, and  sixty-four (39%) had normal pap smear results. Of the 164, only  eighty-four (51%) participated in part 2 of the study and had blood  serum tests performed. A power analysis performed prior to the  initiation of the study showed that 146 women were required to  demonstrate a difference in response rate from 30% in the control group  (normal pap smears) to 50% or more in the treatment group (abnormal pap  smears), with a power of 0.80 or a significance level of 0.05.

Of the eighty-four participants who took the blood test, forty-one  (48.8%) were in the abnormal group and forty-three (51.1%) were in the  normal group.

A total of 35 women from both groups were found to have an  antioxidant deficiency. The number of women deficient in one or more of  the vitamins measured was higher in the abnormal group (20 in the  abnormal group compared to 15 in the normal group). A total of five (5)  participants were deficient in more than one of the vitamins measured.

The analysis of blood tests to determine deficiencies in the normal  versus abnormal group was not statistically significant, p= 0.0676 with a  relative risk of 0.9945 when results of vitamins E, C, and beta  carotene were combined.

When vitamin results were looked at individually, the results were:  Vitamin C p= 0.44, Beta Carotene p= 0.54, Vitamin E gamma p= 0.51. One  vitamin result showed statistical significance, Vitamin E alpha p= 0.04,  but higher, (rather than lower) than the normal level, indicating no  deficiency. Upon investigation, it was determined that only one  participant had an abnormally high level which could be attributed to  abnormal lipid levels. When reviewing the questionnaire, this  participant was not taking any vitamin supplements at the time she  completed the questionnaire, therefore the possibility of overdosing was  eliminated.

The total number of sexual partners in the abnormal group (8.7) was  higher than in the normal group (4.8), p= 0.0072 and was very  significant.

Forty-three (26.2%) of the participants had sex prior to age 16.  Twenty-nine (17.6%) had abnormal pap smears. The incidence of abnormal  pap smears in women who had sex prior to 16 years of age when compared  to those who had sex after 16 years of age was not statistically  significant, p= 0.08.

Thirty-nine of the participants were smokers. Twenty-seven percent  (27%) of the smokers had abnormal pap smears and 18.7% of the smokers  had normal pap smears. When comparing the number of smokers in the  abnormal group to the number of smokers in the normal group, the results  were not statistically significant, p= 0.07.

The use of oral contraception was not surveyed in this study,  therefore, it is unknown if participants used oral contraception as  their birth control method. However, oral contraception is a known  co-factor that may modulate the risk of progression from HPV infection  to HSIL or cervical cancer.

Forty-one (25%) of the participants had other types of sexually  transmitted diseases and 39 (23.7%) had both an STD and HPV. All but two  of the participants with STDs were in the abnormal pap smear group.

Ninety-six (58.5%) out of the 164 participants indicated that they  ate a reasonably balanced diet. Vitamin deficiencies were found in 19 of  the participants who indicated that their diets were reasonably  balanced, and 17 of these participants were in the abnormal pap group.  Since the term “reasonably balanced” is self-interpretative, the 19  participants who assumed that their diets were reasonably balanced yet  still displayed deficiencies were advised to obtain nutritional  counseling.

Supplementation, sleep patterns, exercise, and alcohol/drug use were  also measured. The abnormal pap smear group took fewer vitamins, slept  less than 8 hours per night and exercised less than the normal pap smear  group. The abnormal group also consumed more alcohol, used more drugs  and smoked more than the normal group.

The sample size for the second arm of the study (the blood test) was  not adequate to meet the number required for a power of 0.05; therefore,  the lack in sufficient numbers of participants weakened the results.

Known risk factors for HPV cervical changes, such as number of sexual  partners, held true for this sample population of women with abnormal  pap smears. High risk behaviors, such as smoking and age at first  coitus, although not statistically significant, were very close.

There were slight differences in the nutritional habits of the two  groups. There were more high protein/low carbohydrate diets, reasonably  balanced and vegetarian diets and less junk foods consumed in the group  with normal pap smears (see appendix L). However, vitamin deficiencies  were present in both groups.

The results of this study did not provide new or additional evidence  correlating nutrition, vitamin deficiency and cervical changes in women.  To deter the risk of the progression of HPV cervical changes to  cervical cancer, women should have follow-up appointments with their  doctors following diagnosis of HPV, avoid or stop smoking, practice safe  sex, use a birth control method other than oral contraception, and  increase their daily intake of antioxidants through food and  supplementation.

    1. Center for Disease Control and Prevention, Division of STD Prevention, Prevention of Genital HPV Infection and Sequelae: Report of an External Consultants Meeting, Atlanta,Georgia, December 1999

    2. Center for Disease Control and Prevention, Tracking the Hidden Epidemics, Trends in STDs in the United States 2000., Atlanta, Georgia, 2000

    3. Tortolero-Luna, Guillermo. “Cervical Therapeutic Issues in Gynecologic Cancer”. Journal of Hematology/Oncology Clinics of North America (1999): 13-1

    4. Palon, P.R., Romney, S.L., Mikhail, H. “Decreased Plasma Beta-Carotene Levels in Women with Uterine, Cervical dysplasia and cancer”. Journal of the National Cancer Institute, 80-6: 454-455, 1988

    5. Slattery, M.L., Abbott, T.M. Overall, J.C. “Dietary Vitamin A, C and E and Selenium as Risk Factors for Cervical Cancer”. Epidemiology 1 (1): 8-15, 1990

    6. Food Standard Agency-Healthier Eating- Teenagers (on-line) available from http://www.food.gov.uk/helathiereating/teenagers/.

    7. Fife, H.K. “Human Papillomavirus Vaccine development”. PMID: 9842094

    8. MacDermid, Alan. “Fruit and Vegetables, the main allies in cancer battle”. (on-line) available from http//www.theherald.co.uk/news/archive/22-8-19100-23-34-42. html.

    9. Willett, W.C. “Goals for Nutrition in the Year 2000”. CA Cancer J. Clin. 1999 Nov-Dec; 49 (6):327-30.

    10. Hellberg, D., Nillsson, S., Haley, N.J. “Smoking and Cervical Intraepithelial Neoplasia: Nicotine and Cotinine in Serum and Cervical Mucus in Smokers and Nonsmokers”. American Journal of Obstetrics and Gynecology (1998): 158(4): 910-913

    11. Sunnybrook and Women’s College Health Sciences Center. “Prevention, Cervical Cancer Health Centre (on-line) available from http://www.womenshealthmatters.ca/centres/cancer/cervical/prevention

    12. Kurman, Robert. “Human Papillomavirus, What Role Does it Play in Cervical Cancer”. The Female Patient. September 1990 Volume 15.

    13. Simone, Charles B. Cancer and Nutrition: a ten-point plan to reduce your risk of getting cancer, New York, Avery Publishing, 1994

    14. Burton, G.W., Ingold, K.U. “Beta Carotene: an unusual type of lipid antioxidant”. Science 224 (4649): 569-573, 1984.

    15. Vousden, Karen. “Human Papillomavirus and Cervical Carcinoma”. Cancer Cells. October 1989 Volume 1, Number 2.

    16. Cancer Chemoprevention Part 1: Retinoids and Carotenoids and Other Classic Antioxidants. (on line) available from http://www.intouchlive.com/journals/oncology/o9811d.htm.

    17. Guiliano, A.R., Papanfuss, M., Nour, M., Confield, L.M. Schneider, A., Hatch, K. “Antioxidant Nutrients: Association with persistent human papallomavirus infection”. PMID: 9367065

    18. National Cancer Institute. “Prevention of Cervical Cancer”. (on-line) available from http://www.mcb.uni-bonn.de/cancernet/304734.html

    19. Center for Disease Control and Prevention, Division of STD, STD Prevention, Genital HPV Infection, Atlanta, Georgia, May, 2001

Articles

Human Papillomavirus has emerged as a distinct cause of cervical changes in young women. Its prevalence is continuously growing and is considered at epidemic proportions with 20 million Americans already infected and 5.5 million new cases reported annually. (2) (Center for Disease Control and Prevention, Tracking the Hidden Epidemics., Trends in STDs in the U.S. 2000, Atlanta, Georgia, 2000)

Danielle Luciano, MD

Articles

The Correlation Between Lifestyle, Nutrition, Vitamin Deficiency and HPV Induced Cervical Changes