Management of Cervical Dysplasia and Human Papillomavirus
1/14/2013
Marianne Marchese, ND
The least invasive, most natural, safe and effective treatments that address the cause should be offered
Monday, January 14, 2013
by: Marianne Marchese, ND

Section: Women's Health



Marriane Marchese, ND

Dr. Marchese is the author of 8 Weeks to Women's Wellness. She maintains private practice in Phoenix AZ and teaches Gynecology at Southwest College of Naturopathic Medicine. She was named in Phoenix Magazine's Top Doctor Issue as one of the top naturopathic physicians in Phoenix. Learn more at www.drmarchese.com.
In the 1950’s George Papanicolaou and Herbert Traut developed a test to screen for cervical cancer in women called the pap smear test. This was at a time when cervical cancer was the leading cause of death in women in the United States. Currently, cervical cancer ranks 13th on the list of causes of death in women in the U.S. Thanks to the pap smear test precancerous lesions, called dysplasia, are diagnosed more frequently than invasive cervical cancer. Annual screening and early diagnosis give physicians a chance to start treatment and prevent cervical cancer. Some risk factors for cervical cancer include1:
  • Multiple sexual partners
  • Young age at first intercourse (<16)
  • Having intercourse with uncircumcised partner
  • Unprotected intercourse
  • Human papillomavirus
  • Chlamydia and HIV
  • Immunocompromised
  • Smoking
  • Poor nutritional status
  • Diethylstilbestrol (DES) exposure
  • Long term oral contraceptive use (>5 years)
  • Low socioeconomic status
  • Lack of access to health care or health insurance
  • Rural residence
The main risk factor for cervical cancer is the presence of human papillomavirus (HPV) infection. It is estimated that cervical infection with one of 15 HPV types account for all cervical cancers.2 HPV type 16 is the most common carcinogenic HPV type detected in women with cervical cell changes including precancerous lesions and cancerous lesions. Other HPV types implicated in cervical cancer include; 18,31,33,35,39,45,51,52,56,58,59,66,68,73,and 82.2
"...an alternative approach to managing...pap results & cervical epithelial neoplasia...begins by educating the patient on safe sex practicing to decrease transmission of HPV, HIV and other sexually transmitted diseases..."

It is important to screen women for high risk HPV along with their annual pap smear which screens for cervical cell abnormalities. HPV testing can be performed during the pap smear. Most pap smear cytology is now done with liquid based cytology using the Thin Prep or SurePath vial which has the ability to test for both cervical cytology and HPV. A separate swab test for HPV also exists and is called the Digene probe. We now can identify the exact high risk strain a woman has by running an additional test for HPV genotype.

Screening
Recently the American College of Obstetricians and Gynecologists, ACOG, made the following changes in regards to screening guidelines for how often a woman should get a PAP smear.3 The new guidelines recommend less frequent screening for certain age groups.
  1. Women ages 21 to 30 will be screened every two to three years instead of every year.
  2. Women age 30 and older who have had three consecutive negative cervical cytology test resultsand who have no history of moderate cervical dysplasia (CIN 2) or severe cervical dysplasia (CIN 3), are not HIV infected, are not immunocompromised, and were not exposed to DES in utero may be screened once every three to five years.
  3. Women of any age with certain risk factors may need more frequent screening, including those who have HIV, are immunosuppressed, were exposed to diethylstilbestrol (DES) in utero, and have been treated for cervical intraepithelial neoplasia (CIN) 2, CIN 3, or cervical cancer.
  4. Women over the age of 30 should have both cervical cytology test and high risk HPV testing. This is referred to as combination test.
  5. Women under 30 should be tested for high risk HPV if the pap comes back as atypical cells of undetermined significance, or ASCUS. This is called reflux testing and can be done from the same sample if liquid based cytology is done.
  6. It is acceptable to discontinue cervical cancer screening between 65 years and 70 years of age in women who have three or more negative cytology test results in a row and no abnormal test results in the past 10 years.
In the past ACOG recommended that cervical screening begin three years after first sexual intercourse or by age 21, whichever occurred first. Moving the baseline cervical screening to age 21 avoids unnecessary treatment. Although HPV infection is high among sexually active adolescents, invasive cervical cancer is rare. The immune system clears the HPV infection within one to two years among most adolescents. The large majority of cervical dysplasia in adolescents resolves on its own without treatment.

Treatment
Conventional management for cervical dysplasia includes colposcopy with endocervical sampling to determine the extent and degree of dysplasia which is categorized as cervical intraepithelial neoplasia, CIN, and graded level I, II, or III.4 The American Society for Coloposcopy and Cervical Pathology, ASCCP, has determined guidelines for conventional management of cervical intraepithelial neoplasia. They include;5
  • CIN I and satisfactory colposcopy- Follow-up without treatment with PAP and HPV test at 6 months. This is called ‘watch and wait.’ If still positive repeat the colposcopy. Alternative approach is to follow-up at 12 months with repeat colposcopy. A third approach is to treat immediately with cryotherapy or a loop electrosurgical excision procedure,LEEP.
  • CIN I and unsatisfactory coloscopy- diagnostic excisional procedure (cone biopsy)
  • CIN II and III with satisfactory colposcopy- LEEP or diagnostic excisional procedure
  • CIN II and II with unsatisfactory colpo- diagnostic excisional procedure (cone biopsy)
The goal is to remove the abnormal cells and shed the top layer that holds the virus. But, the virus is in the body and conventional treatmentsdon’t treat the whole body, support the immune system, or systemically treat HPV. Also, there are complications from cryotherapy and LEEP that will make pregnancy and child birth more difficult.

There are options
Naturopathic physicians offer an alternative approach to managing both abnormal pap results and cervical epithelial neoplasia. Addressing the cause is key to treating the disease. This begins by educating the patient on safe sex practicing to decrease transmission of HPV, HIV and other sexually transmitted diseases. Smoking is linked to cervical cancer as it increases the duration of infection with high risk HPV.6 Smoking also weakens the immune system. Smoking cessation and supporting the immune system are an important part of treatment for cervical dysplasia.  Poor nutritional status is linked to cervical cancer. Folate and B12 deficiency has been associated with increased HPV infection.7 Low serum retinol levels has been linked to increased risk of cervical epithelial neoplasia.8 A comprehensive nutritional intake and dietary counseling should be included in treatment.

No need to watch and wait
When the pap comes back with ASC-US and no HPV, normal cytology with HPV present, or ASC-US with HPV in the younger women, conventional medicine suggests to watch wait and repeat the pap. This is where naturopathic medicine would begin treatment. Supporting the immune system to fight off HPV as well as treating HPV directly can reverse the low grade cervical cell abnormality and eliminate HPV. Guidelines for referral to colposcopy are the same.

Naturopathic medicine can also treat cervical intraepithelial neoplasia I and II. This treatment consists of oral systemic support as well as local vaginal treatment of the cervix. Some important herbal medicines and nutrients to consider include:

Folic acid
There have been several studies showing low serum folate levels are linked to cervical dysplasia and high folate blood levels are linked to the prevention of CIN I.9,10 Improvement in cervical dysplasia using folic acid supplementation is also well documented.11 The doses vary and are most often given with vitamin B12 as not mask B12 anemia.

Indole-3-carbinol
Indole-3-carbinol (I3C) is present in all members of the cruciferous vegetable family including cabbage, broccoli, Brussels sprouts, cauliflower, and kale. Studies indicate I3C has the potential to prevent and even treat a number of common cancers, especially those that are estrogen related.12 In a double-blind, placebo controlled study, 30 patients with biopsy-confirmed CIN II-III were randomized to receive placebo or 200 or 400 mg oral I3C daily for 12 weeks. Three patients did not complete the study. None of the 10 patients in the placebo group had complete regression of CIN. Four of eight patients in the 200-mg/day group and four of nine in the 400-mg/day group had complete regression of CIN.13 I3C is easily available over the counter as a supplement or simply by eating 4-5 servings of the cruciferous family vegetables a day.

Antioxidants
Antioxidants are known for their cancer prevention properties. Studies have linked antioxidant levels to CIN and cervical cancer. In one study, blood levels of coenzyme Q10 (CoQ10) and vitamin E were measured in patients with biopsy-confirmed CIN, cervical cancer, and in controls with normal PAP smears. Results showed levels of CoQ10 and Vitamin E were significantly lower in patients with diagnosed CIN and cervical cancer when compared to controls.14 Levels of CoQ10 from cervicovaginal epithelial cells were measurable and also appeared to be significantly lower in women diagnosed with CIN.15 These findings suggest low levels of these two antioxidants may play a role in the pathogenesis of cervical dysplasia.

Vitamin C
Vitamin C is an excellent antioxidant that boosts the immune system and has proven anti-cancer effects. It is known that women with cervical dysplasia have low blood levels of vitamin C.16 A recent studied showed that women with high intake of dietary vitamin C had a reduction in the risk of cervical dysplasia.17 A study on Korean women looked at 58 colposcopy confirmed cases of CIN and compared them to 86 women with normal pap smears. The plasma concentration of Vitamin C was significantly lower in the CIN group than in the control group.18 This suggests a role for Vitamin C in the treatment of cervical dysplasia.

Green tea extract
Epigallocatechin-3-gallate (EGCG) is the standardized extract from green tea. It is known to inhibit epidermal growth factor receptor which is needed for cervical cell growth. A recent study looked at 51 women with HPV infected cervical lesions divided into 4 groups and compared them to 39 controls. Green tea ointment was applied locally to 27 patients twice a week. For oral delivery, a EGCG capsule was taken orally every day for eight to 12 weeks. In the study, 20 out of 27 patients under ointment therapy showed a response. Six out of eight patients under green tea ointment plus capsule therapy showed a response. Six out of 10 patients under EGCG capsule therapy showed a response. Overall, a 69% response rate was noted for treatment with green tea extracts, as compared with a 10% response rate in untreated controls. A good response meant an improvement in cervical dysplasia.19

Coriolus versicolor
Coriolus is a mushroom commonly used in Asian cultures for its immune properties. It is often called an immunomodulator and has been studied for it is immune enhancing properties in cancer patients undergoing chemotherapy. Recently is has been studied for its immune modulating effects on HPV and reversing early stages of cervical cancer.20 A study published in the Townsend Letter November 2006 by J. Silva Couto looked at women with cervical dysplasia, LSIL (CIN I and HPV). Half of the women in the LSIL group were given 3g/d Coriolus a day for one year and the other half took none. Dr. Silva Couto found that Coriolus versicolor supplementation over a period of one year substantially increased regression of the dysplasia (LSIL) and induced clearance of the high risk sub-types of the HPV virus. Some interesting findings of the study include;

a) Coriolus versicolor supplementation demonstrated a 72% regression rate in LSIL lesions compared to 47.5% without supplementation.

b) Coriolus versicolor supplementation demonstrated a 90% regression rate in the high risk HPV virus sub-types compared to 8.5% without supplementation.


Local treatment applied to the cervix
Escharotic treatment
The use of escharotic or caustic treatments for epithelial cancers is based on a centuries-old observation that select plant and mineral extracts could be used to treat topical skin lesions. Two small studies show the efficacy of this treatment in reversing cervical dysplasia in women.21,22 This treatment is used for CIN I and II after a satisfactory colposcopy is performed and if there is no disease in the endocervical canal and no glandular cells present. Escharotic treatment for cervical dysplasia involves the local application of a natural enzyme, bromelain, to the surface of the cervix. This is left in place for 15 minutes with heat applied to activate the enzyme. The proteolytic properties in bromelain dissolve the top layer of cells on the cervix which are infected and damaged by the HPV virus. A mixture of zinc chloride and a plant Sanguinaria is applied to the cervix to cause sloughing of abnormal tissue. Zinc chloride is caustic and acts to disrupt the cellular membrane integrity and the mucus over coating to allow the Sangunaria to penetrate the cells. Sanguinaria has been shown to have anti-neoplastic qualities.21 The treatment is performed twice per week with at least two days in between treatments for 4-5 weeks. The ZnCl solution is made by a compounding pharmacist.

Vaginal suppository treatment
Vaginal depletion packs have been in use since the 1800s. Vaginal depletion packs, Vag pak, work by the action of the substances within the packs, which draw infection out of the cervical cells and boast the immune system. Each suppository contains: magnesium sulfate, glycerin complex, hydrastis tincture, thuja oil, tea tree oil, bitter orange oil, vitamin-A (as palmitate) 100,000 iu, ferric sulfate,ferrous sulfate in polybase. Hydrastis canadensis is effective against many microbial pathogens, as are the essential oils of tea tree, thuja and bitter orange.Vag Pak suppositories are often used for mild dysplsia and/or high risk HPV.

Green tea suppositories made from a pharmacy are also effective for cervical dysplasia and HPV. ECGC in green tea was evaluated on cervical epithelial; cells and cervical cancer cells and HPV. Green tea inhibited cancer cell growth, induced apoptosis, decreased gene expression, and cell cycle changes.23 As mentioned earlier green tea has been shown to be effective against HPV.

Critics of natural medicine say there is no published evidence that these options work or are backed in science. There are several recent published articles explaining the science and patient outcomes. One can be found at http://www.ncbi.nlm.nih.gov/pubmed/19679625

Summary
It is important that a woman is informed of her options for managing cervical health. The least invasive, most natural, safe and effective treatments that address the cause should be offered. There are times natural medicine is not an option for treating cervical cell changes due to the severity and location of disease but in many cases naturopathic treatment of cervical dysplasia and HPV is the safest and most effective option.

References
1. Synder U. A look at cervical cancer. Medscape OB/GYN & Women’s Health. 2003;8(1):1-12
2. Wheeler C. Advances in primary and secondary interventions for cervical cancer: prophylactic human papillomavirus vaccines and testing. Nat Clin Pract Oncol. 2007;4(4):224-235.
3. ACOG.org
4. Wright TC, et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J OB/GYN 2007;11:346-355.
5. Wright TC, et al. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma-in-situ. Am J OB/GYN 2007;11:340-345.
6. Synder U. A look at cervical cancer. Medscape OB/GYN & Women’s Health. 2003;8(1):1-12
7. Weinstein SJ, et al. Low serum and red blood cell folate are moderately, but nonsignificantly associated with increased risk of invasive cervical cancer. J Nutr. 2001;131:2040-2048.
8. Schiff MA, et al. Serum carotinoids and risk of cervical epithelial neoplasia in southwestern American women. Cancer Epidemiol Biomarkers Prev. 2001;10:1219-1222.
9. Piyathilake CJ, et al. Lower risk of cervical intraepithelial neoplasia in women with high plasma folate and sufficient vitamin B12 in the post-folic acid fortification era. Cancer Prev Res. 2009;2(7):658-664.
10.Piyathilake CJ, et al. Lower red blood cell folate enhances the HPV-16-associated risk of cervical intraepithelial neoplasia. Nutrition. 2007;23(3):203-10.
11. Marshall K. Cervical dysplasia: early intervention. Altern Med Rev. 2003;8(2):156-70.
12. Grubbs CJ, Steele VE, Casebolt T, et al. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer Res 1995;15:709-716.
13. Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol 2000;78:123-129.
14. Palan PR, Mikhail MS, Basu J, Romney SL. Plasma levels of antioxidant beta-carotene and alpha-tocopherol in uterine cervix dysplasias and cancer. Nutr Cancer 1991;15:13-20.
15. Mikhail MS, Palan PR, Romney SL. Coenzyme Q0 and alpha tocopherol concentrations in cervical intraepithelial neoplasia and cervix cancer. Obstet Gynecol 2001;97:3S.
16. Hudson T. Women’s encyclopedia of natural medicine. Keats Publ. 1999.
17. Ghosh C, et al. Dietary intakes of selected nutrients and food groups and risk of cervical cancer. Nutr Cancer. 2008;60(3):331-41.
18. Lee Gj, et al. Antioxidant vitamins and lipid peroxidation in patients with cervical intraepithelial neoplasia. J Korean Med Sci. 2005 Apr;20(2):267-72.
19. Ahn ws, et al. The protective effects of green tea extract on human cervical lesions. Eur J cancer prev 2003;12(5):383-390
20. Bogdanova J. [Coriolus versicolor--innovation in prevention of oncogynecological diseases, especially HPV]. Akush Ginekol (Sofiia). 2008;47 Suppl 3:51-3.
21.Hudson TS. Consecutive case study research of carcinoma in situ of cervix employing local escharotic treatment combined with nutritional therapy. J Naturopathic Med 1991;2:6-10.
22. Hudson TS. Escharotic treatment for cervical dysplasia and carcinoma. J Naturopathic Med 1993;4:23.
23. Zou c, et al. Green Tea Compound in Chemoprevention of Cervical Cancer Int J Gynecol Cancer. 2010 ;20(4):617-624
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