Management of Cervical Dysplasia & Human Papillomavirus

In the 1950s, George Papanicolaou and Herbert Traut developed a test to screen for cervical cancer in women, called the Pap smear. At the time, cervical cancer was the leading cause of death in women in the US; now it ranks only 13th. Thanks to the Pap 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 include: (1)

• multiple sexual partners
• young age at first intercourse (under 16)
• intercourse with uncircumcised partner
• unprotected intercourse
• human papillomavirus
• chlamydia and HIV
• poor nutritional status
• compromised immune system
• smoking
• diethylstilbestrol (DES) exposure
• long-term oral contraceptive use (over 5 years)
• low socioeconomic status
• rural residence
• lack of access to health care or health insurance

The main risk factor for cervical cancer is the presence of human papillomavirus (HPV) infection. It is estimated that cervical infection with one of 16 HPV types accounts for all cervical cancers.(2)  HPV type 16 is the most common carcinogen detected in women with cervical cell changes including precancerous and cancerous lesions. HPV type 18 is the second most common type found in women with cervical cancer as well as adenocarcinomas. The other HPV types implicated in cervical cancer are 31,33,35,39,45,51,52,56,58,59, 66,68,73, and 82.2 These, along with 16 and 18, are called high-risk HPV types. Types 6 and 11, which cause genital warts, are considered low risk because they are not linked to cervical cancer.

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 testing is now done with liquid-based cytology using the ThinPrep or SurePath vials, which can test for both abnormal cervical cells and HPV. There is also a separate swab test for HPV, called the Digene probe.

(Ed. note: For an explanation of the 2009 recommendations by the American College of Obstetricians and Gynecologists in regard to screening women for cervical cell changes and HPV3, visit: https://www.drmarchese.com/articles.html) (3)

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 of adolescents. Although the rate of HPV infection is high among sexually active adolescents, invasive cervical cancer is very rare. The immune system clears the HPV infection within one to two years among most adolescent women. The large majority of cervical dysplasia in adolescents resolves on its own without treatment.

THE PAP CAME BACK ABNORMAL – NOW WHAT?

(Editor’s note: For a detailed description of the different types of abnormalities that may be found by cervical cell screening, along with the conventional medicine treatment protocol recommended for each type of abnormality, visit: https://www.drmarchese.com/articles.html) (4,5)

THE NATUROPATHIC APPROACH TO TREATMENT

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 practising safe sex 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) It also weakens the immune system. Smoking cessation and immune system support 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 have 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 test results come back indicating ASCUS and no HPV, normal cytology with HPV present, or ASCUS with HPV in 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 cervical treatments. Some important herbal medicines and nutrients for systemic treatment include:

• Folic acid: There have been several studies showing that low serum folate levels are linked to cervical dysplasia and high folate blood levels to the  prevention of CIN I (cervical dysplasia).(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 so as not to mask B12 anemia.
• Indole-3-Carbinol (I3C): is present in all members of the cruciferous vegetable family, including cabbage, broccoli, brussels sprouts, cauliflower, and kale. Studies indicate that 13C 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 (moderate to severe cervical dysplasia) were randomized to receive placebo or 200 or 400 mg oral 13C 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) 13C is easily available over the counter as a supplement or simply by eating 4 to 5 servings of cruciferous vegetables a day.
• 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 normal PAP smears (controls). Results showed that levels of CoQ10 and vitamin E were significantly lower in patients with diagnosed CIN and cervical cancer when compared with 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 that low levels of these two antioxidants may play a role in the pathogenesis of cervical dysplasia.
• Vitamin C: is an excellent antioxidant that boosts the immune system and has proven anticancer effects. It is known that women with cervical dysplasia have low blood levels of vitamin C.(16) A recent study 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 with 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 with 39 controls. Green tea ointment was applied locally to 27 patients twice a week. For oral delivery, a EGCG capsule was taken every day for 8 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, compared with a 10% response rate in untreated controls. A good response meant an improvement in cervical dysplasia. (19)
• Coriolus Versicolor: is a mushroom commonly used in Asian cultures for its immune properties. It is often called an immunomodulator and has been studied for its immune enhancing properties in cancer patients undergoing chemotherapy. Recently, is has been studied for its immunomodulating 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 3 grams/day of Coriolus a day for one year and the other half took none. 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 subtypes of the HPV virus. Some interesting findings of the study include the following: Coriolus versicolor supplementation demonstrated a 72% regression rate in LSIL lesions compared with 47.5% without supplementation; Coriolus versicolor supplementation demonstrated a 90% regression rate in the high-risk HPV virus subtypes compared with 8.5% without supplementation.

(Ed. note: For a description of local treatments (involving bromelain enzyme) that can be applied to the cervix, along with vaginal suppositories, see extended version of this article posted at:https://www.drmarchese.com/articles.html) (21,22)

SUMMARY OF NATUROPATHIC TREATMENT OPTIONS

1) education on safe sex practices
2) smoking cessation program
3) nutritional counseling and diet plan
4) support for the immune system
5) systemic treatment: folic acid 5-10 mg day; B12 – 1,000 mcg day; indole-3-carbinol 400 mg day; antioxidants; vitamin C 3-4 g day; green tea extract 1,500 mg day; coriolus versicolor 3,000 mg day.
6) Local cervical treatment

References

(1) Snyder U. A look at cervical cancer. Medscape OBGYN & 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 Oneol. 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 JObstet Gynecol. 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 Obstet Gynecol. 2007; 11 ,340-345.
(6) Snyder U, op cit.
(7) Weinstein SJ et al. Low serum and red blood cell folate are moderately but  not significantly associated with increased risk of invasive cervical cancer. / NUlr. 2001; 131:2040~ 2048.
(8) Schiff MA et al. Serum carotinoids and risk of cervical epithelial neoplasia in southwestern American women. Cancer Epidemiol Biomarkers Prev2001; 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
(11) Marshall K. Cervical dysplasia: early intervention. Altern Med Rev. 2003; 8(2):156-170.
(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 GIN. Gynecol Oncol. 2000
(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;15:1320.
(15) Mikhail MS, Palan PR, Romney SL. Coenzyme Q10 and alpha tocopherol concentrations in cervical intraepithelial neoplasia and cervix cancer. Obstet Gynecol. 2001;97:3S.
(16) Hudson, Tory. Women’s Encyclopedia of Natural Medicine. Keats Publishing; 1999,
(17) Ghosh C et al. Dietary intakes of selected nutrients and food groups and risk of cervical cancer. Nutr Cancer. 2008; 60(3);331-241.
(18) Lee GJ, et aL Antioxidant vitamins and lipid peroxidation in patients with cervical intraepithelial neoplasia. Journal Korean Med Sci. 2005 Apr
(19) Ahn WS et al. The protective effects of green tea extract on human cervical lesions. European Journal Cancer Prevention; 2003; 12(5);383-390.
(20) Bogdanova J. Coriolus versicolor – innovation in prevention of oncogynecological diseases, especially HPV. [In Bulgarian.) Akush Ginekol (Soliia). 2008;47  SuppI3:51-53.
(21) Hudson, Tory. Consecutive case study research of carcinoma in situ of cervix employing local escharotic treatment combined with nutritional therapy. Journal of Naturopathic Med. 1991
(22) Hudson Tory. Escharotic treatment for cervical dysplasia and carcinoma. Journal of Naturopathic Medicine 1993;4,23.

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