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Cervical Dysplasia
Naturopathic and Conventional Strategies
by Tiffany Eberhard, ND
[email protected]
Cervical Dysplasia and its Risk
Factors
Cervical dysplasia refers to abnormal cells
found on the surface of the cervix, that are
considered to be premalignant and can
progress to cancer.[1] Cervical dysplasia is
primarily caused by a sexually transmitted
infection with different strains of the
human papillomavirus (HPV). However,
different strains can be involved in both
benign and malignant lesions; therefore,
the progression of the disease appears
to depend on individual factors. Studies
suggest that HPV exposure is the initiating
event that can lead to the development of
cervical dysplasia, often termed cervical
intraepithelial neoplasia (CIN). HPV is the most common sexually transmitted infection
in the U.S., with up to 80% of the adult population potentially being infected.[3, 4] HPV
is transmitted through skin-to-skin contact, and therefore condoms do not provide full
protection; however, they can increase the likelihood of regression. The majority of genital
HPV infections don’t cause symptoms, are often transient, and resolve spontaneously
since the host’s immunity is able to defend against clinical disease.[4] However, some
cases do progress to cause abnormal cells, including cervical dysplasia and/or cervical
cancer. Cervical dysplasia is treatable in its noninvasive state.[3]
Even though HPV is the primary risk factor for cervical cancer and plays a role in cervical
cancer development, other specific risk factors are associated with the development of
cervical dysplasia. These include early sexual activity, multiple sexual partners, sexually
transmitted diseases, oral contraceptive use, cigarette smoking, low socioeconomic
status, immunosuppression, and poor diet Epidemiological and laboratory studies
have suggested nutritional factors may play an important role in the development and
progression of CIN and cervical cancer; therefore, primary prevention should focus
on risk reduction. The most important way to reduce risk is to eliminate risky sexual
behavior that increases exposure to HPV. Females are most susceptible to potential
cancer development during adolescence and young adulthood due to the biological
changes that occur in the cervix during puberty.[2, 5] It is important to recognize that
cervical dysplasia is not just a localized cervical tissue health issue, but actually involves
the immune system health and the individual’s resistance to viral exposure. [3] Oral
contraceptives are known to potentiate the adverse effects of cigarette smoking and
decrease several nutrients including vitamins C, vitamins B6 and B12, folic acid, riboflavin,
and zinc.[4]
Cervical Cancer
Squamous-cell cervical cancer is almost
always preceded by cervical dysplasia.[3]
Cervical cancer is the second most common
cancer in women between the ages of 20
and 39.[2, 6] Cervical cancer is associated
with long-term persistent HPV infection.[4]
There are over 50 strains of HPV, with the
high-risk strains being 16, 18, and 31.
These specific strains are associated with
severe cervical dysplasia (CIN III) and cancer of the cervix, vulva, penis, and perineum.[2]
The time it takes from exposure to the appearance of a lesion or an abnormal Pap
smear varies from a few weeks to decades.[4] Symptoms of cervical cancer usually
appear once the cancerous cells invade nearby tissue and include abnormal bleeding
that occurs between regular menstrual periods, after sexual intercourse, douching, or a
pelvic exam. Other symptoms may include bleeding after menopause, increased vaginal
discharge, heavier and/or longer menstrual bleeding, and pain during intercourse.[1]
Diet and Nutritional
Supplementation
beta-Carotene and Vitamin A
Increased consumption of fruits and
vegetables containing antioxidants
is associated with lower risks for
malignancies.[2] Higher consumption of
vegetables is associated with a 54%
decrease in risk of HPV persistence.[3] Fruits
and vegetables are the primary dietary
source of carotenoids, vitamin C, and
folate, which may have synergistic effects in cancer prevention. Increased intake of
foods rich in vitamin A, especially high-retinol foods such as carrots and spinach,
may reduce the risk of developing early stage cancer while the high intake may inhibit
progression to a more invasive form of this disease.[2] Retinol intake and serum retinol
levels have been found to be 4–5 times lower among women with cervical dysplasia
who progress to in situ or invasive disease compared to women who experience disease
regression.[2, 7] Additionally, beta-carotene deficiency in the cervical cells has been linked
to the development of cervical dysplasia; however, supplementation does not appear to
have an effect.[3, 8] It has been shown that 6% of patients with untreated cervical cancer
have below-normal serum vitamin A levels.[4] There is a three times greater risk of severe
dysplasia when serum beta-carotene levels are low, and the severity of the dysplasia
seems to correlate to the low level of beta-carotene.[4, 9, 10] Carotenes and retinols
improve the integrity and function of the epithelial tissues, act as antioxidants, and
improve immune system function.[4] Vitamin A and its analogues inhibit the proliferation
of HPV infection via programmed cell death, also known as apoptosis, and inhibition of
cell growth rates in laboratory studies.[3]
Indole-3-Carbinol (I3C)
I3C is the phytochemical present in the members of the cruciferous vegetable family,
which includes cabbage, broccoli, Brussels sprouts, cauliflower, and kale. I3C has been
used to prevent and treat a number of cancers, especially those that are estrogenrelated. I3C is converted to diindolylmethane (DIM) in the body and may be the
predominant active agent. I3C can prevent transformation and/or tumor progression and
can kill transformed cells selectively.[2] I3C can act in several ways to prevent abnormal
cell growth and prevent tumor progression.[3] It has been demonstrated that women
with moderate (CIN II) and severe (CIN III) dysplasia have lower 2‑hydroxyestrone:16
alpha‑hydroxyestrone ratios than women with no abnormal cervical pathology.[2, 11] I3C
and DIM are able to achieve apoptosis in the cervical tissue of mice, and therefore show
promise for the treatment of cervical dysplasia.[2, 12]
Folate/Folic Acid
Folate deficiency has been linked to cervical dysplasia.[2] It is thought that folate deficiency
allows the HPV to be more easily incorporated into a person’s DNA.[2, 13] Deficiency impairs
DNA synthesis, which is crucial to cell reproduction, growth, and differentiation. Tissues that
are low in folate are at risk of developing weak areas of DNA, which increases attachment
by carcinogens and viruses, increases potential for chromosomal damage and cancerpromoting gene expression, and inhibits DNA repair.[2] Low levels of folic acid in the blood
have been associated with a moderately increased risk of invasive cervical cancer.[3] Folic
acid deficiency is common and oral contraceptive use increases the risk of deficiency.[4]
Folate has been used in women with mild and moderate cervical dysplasia, and has been
shown to improve or normalize cytologic smear in patients with cervical dysplasia.[3, 4]
Green Tea
Two constituents of green tea, polyphenol E and epigallocatechin-3‑gallate (EGCG),
have been effective against HPV-infected cervical cells and lesions. These constituents
have antitumor effects.[3] The use of EGCG or high green tea consumption could reduce
the incidence of cervical cancer or delay the progression of precancerous lesion.[14]
Conventional Strategies
Pap smears play the most important
role in the prevention of cervical cancer
and in detecting milder grades of
cervical dysplasia.[3] Annual screening is
recommended for women up to the age
of 29, with the time between Pap smears
increasing to 2 to 3 years after this age.
Screening generally begins 3 years after
the onset of vaginal intercourse and should
occur no later than 21 years of age.
Since regular PAP smears are currently part of our health-care model, cervical dysplasia
is generally discovered before it becomes an invasive cervical cancer. If a Pap result
comes back abnormal, patients are told to have a repeat Pap in six months to see if the
lesion spontaneously remits.[2]
If another abnormal Pap smear is obtained, the next step is a referral to a gynecologist
to have a colposcopy. Colposcopy involves the use of a scope in order to visualize the
cervix while white vinegar is applied to the tissue to detect abnormal tissue. The table
below summarizes the potential results of a Pap smear and their meaning, as well as
recommended course of action.[3]
Atypical squamous cells of Mild abnormality. HPV testing is recommended.
undetermined significance
(ASC-US)
Atypical squamous cells, High-grade (precancerous) lesions cannot be ruled out.
high grade (ASC-H)
Women with this result are at a greater risk for CIN II or III.
Colposcopy and biopsy in addition to HPV testing is
recommended.
Low-grade squamous Mild abnormality that involves changes in the size, shape,
intraepithelial lesion (LSIL) and number of abnormal cells.
Colposcopy and biopsy are recommended.
High-grade squamous More severe and serious than LSIL, and have a higher
intraepithelial lesions (HSIL) likelihood of progressing to cervical cancer.
Colposcopy and biopsy are recommended.
If the biopsy shows dysplasia, ablation or destructive procedures may be considered.
These include cryotherapy, carbon-dioxide laser, and electrocautery. Removal procedures
are another option, and include cone biopsy and loop electrosurgical excision procedure
(LEEP). All of these procedures remove the dysplastic cells and allow new cells to replace
the old ones. They have a success rate of approximately 90% when used correctly.
Despite these techniques being relatively safe and effective in preventing future cervical
cancer, their effects on future fertility and pregnancy outcomes remain unclear.[3]
The HPV vaccine targets two of the main strains that are commonly associated with
cervical cancer, and other strains associated with genital warts. HPV‑16 vaccine has
reduced the incidence of both HPV‑16 infection and HPV‑16–associated cervical
dysplasia.[3]
Conclusion
In conclusion, there are many risk factors associated with the development of cervical
dysplasia and cervical cancer. Nutritional supplementation may be a worthwhile treatment
approach in the noninvasive stages of this disease. It is absolutely critical to have an
accurate diagnosis and sufficient evaluation in order to determine the best treatment
course.[3]
References
1.
Johns Hopkins Medicine. The Sidney Kimmel Comprehensive Cancer Center. What is Cervical Dysplasia? ∙ http://www.hopkinsmedicine.org/
kimmel_cancer_center/centers/cervical_dysplasia/about_cervical_dysplasia.html
2.
Marshall, K. “Cervical dysplasia: early intervention”. Alternative Medicine Review Vol. 8, No. 2 (2003): 156–170.
3.
Hudson, T. Women’s encyclopedia of natural medicine: Alternative therapies and integrative medicine for total health and wellness. New York:
McGraw-Hill, 2008, 500 p.
4.
Pizzorno, J.E., and T.M. Murray. Textbook of natural medicine Volume 1, 3rd edition. St. Louis: Churchill Livingstone, 2005.
5.
Roye, C.F. “Pap smear screening for adolescents: rationale, technique and follow-up”. Journal of Pediatric Health Care Vol. 7, No. 5 (1993):
199–206.
6.
Greenlee, R.T., et al. “Cancer statistics, 2001”. CA: A Cancer Journal for Clinicians Vol. 51, No. 1 (2001): 15–36.
7.
Nagata, C., et al. “Serum retinol level and risk of subsequent cervical cancer in cases with cervical dysplasia”. Cancer Investigation Vol. 17, No. 4
(1999): 253–258.
8.
Palan, P.R., et al. “Plasma levels of beta-carotene, lycopene, canthaxanthin, retinol, and alpha- and tau-tocopherol in cervical intraepithelial
neoplasia and cancer”. Clinical Cancer Research Vol. 2, No. 1 (1996): 181–185.
9.
Orr, J.W. Jr, et al. “Nutritional status of patients with untreated cervical cancer, II. Vitamin assessment”. American Journal of Obstetrics and
Gynecology Vol. 151, No. 5 (1985): 632–635.
10. Wylie-Rosett, J.A., et al. “Influence of vitamin A on cervical dysplasia and carcinoma in situ”. Nutrition and Cancer Vol. 6, No. 1 (1984): 49–57.
11. Newfield, L., et al. “Estrogen metabolism and human papillomavirus–induced tumors of the larynx: chemo-prophylaxis with indole-3‑carbinol”.
Anticancer Research Vol. 13, No. 2 (1993): 337–341.
12. Chen, D.Z., et al. “Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV 16-transgenic
preneoplastic cervical epithelium. The Journal of Nutrition Vol. 131, No. 12 (2001): 3294–3302.
13. Butterworth, C.E. Jr, et al. “Folate deficiency and cervical dysplasia”. JAMA Vol. 267, No. 4 (1992): 528–533.
14. Ahn, W.S., et al. “Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions”. European Journal of Cancer
Prevention Vol. 12, No. 5 (2003): 383–390.