Source: Ahn WS, et al. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur J Cancer Prev 2003;12:383-390.
Abstract: The authors investigated clinical efficacy of green tea extracts (polyphenon E; poly E and (-)-epigallocatechin-3-gallate [EGCG]) delivered in a form of ointment or capsule in patients with human papilloma virus (HPV)-infected cervical lesions. Fifty-one patients with cervical lesions (chronic cervicitis, mild dysplasia, moderate dysplasia, and severe dysplasia) were divided into four groups, as compared with 39 untreated patients as a control. Poly E ointment was applied locally to 27 patients twice a week. For oral delivery, a 200 mg of poly E or EGCG capsule was taken orally every day for eight to 12 weeks. In the study, 20 out of 27 patients (74%) under poly E ointment therapy showed a response. Six out of eight patients under poly E ointment plus poly E capsule therapy (75%) showed a response, and three out of six patients (50%) under poly E capsule therapy showed a response. Six out of 10 patients (60%) under EGCG capsule therapy showed a response. Overall, a 69% response rate (35/51) was noted for treatment with green tea extracts, as compared with a 10% response rate (4/39) in untreated controls (P < 0.05). Thus, the data collected here demonstrated that green tea extracts in a form of ointment and capsule are effective for treating cervical lesions, suggesting that green tea extracts can be a potential therapy regimen for patients with HPV-infected cervical lesions.
Comments by Mary L. Hardy, MD
Green tea, made from lightly steamed leaves of the Camellia sinensis plant, is one of the most popular beverages in the world. Steaming green tea leaves prevents the enzymatic breakdown of the polyphenol components, also known as catechins, which are thought to be responsible for its medicinal effects. The catechins in general account for up to 40% of the dry weight of tea and epigallocatechin gallate (EGCG) is the most prominent catechin.
Epidemiological studies have shown an inverse relationship between amount of tea consumed and rates of a number of cancers including oral-pharyngeal, gastric, esophageal, colorectal, pancreatic, prostate, and some urinary tract carcinomas.1 The evidence for the protective effects of tea are strongest in Asian populations, who mainly drink green tea. The amount of green tea needed to show a positive preventive effect has been as high as 10-14 cups/d in some studies.1 Given the high dose needed to show benefit, there has been great interest in developing highly concentrated, generally decaffeinated green tea extracts. An average cup of tea contains 300-400 mg, and many commercial extracts—which contain more than 90% polyphenols, mainly EGCG, and are equivalent to 2-6 cups of green tea—are being prepared.
For women in particular, there has been relatively little evidence that tea decreases cancer risk. The Iowa Women’s Health Study showed that tea consumption decreased the rate of rectal cancer, but did not decrease the incidence of any gynecological cancers.2 The tea consumed in this study was mainly black tea, which may account for the general lack of effect observed. This possibility is supported by the findings of a case-control study in China that showed a decreased risk in the incidence of developing ovarian carcinoma with increased consumption of green tea.3 Finally, a Japanese observational study showed that a high rate of green tea consumption (> 5 cups/d) was associated with an improved prognosis in patients presenting with stage I and II breast cancer.4
A common gynecological malignancy, cervical cancer, has become, in the developed world, a generally preventable disease, thanks to effective screening. Incidence in the United States of new cases and death are relatively low compared to more common cancers in women, such as breast or lung.5 However, for certain populations (HIV-positive or other immunocompromised women) or those in developing countries, cervical cancer can represent a significant disease burden—80% of the new cervical cancer cases reported worldwide are reported in developing countries.6 Therefore, interest would be high in a natural, low-cost, non-toxic treatment that could interrupt the progression from dysplasia to malignancy in women with cervicitis.
Eighty-eight women were enrolled in a randomized study to test the effect of poly E ointment, poly E capsules, and ECGC capsules on morphological changes in patients with documented HPV-related cervical changes.7 All women were demonstrated to have either atypical squamous cells of unknown significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), or high-grade squamous intraepithelial lesions (HSIL) by pap smear. Patients were treated with either active therapy or customary care (observation) for 8-12 weeks. The four active therapy groups included: poly E ointment alone applied topically twice a week directly to abnormal cervical tissue, poly E ointment plus oral poly E capsules (200 mg/d), poly E capsules alone, or another ECGC capsule at the same 200 mg/d dose. Poly E is a high polyphenol content, decaffeinated, proprietary green tea extract. Results of therapy were evaluated by repeat pap smear, biopsy of lesion, HPV testing, and general response to therapy as determined by their change in degree of atypia or dysplasia.
The design of this study was complex (multiple interventions and multiple degrees of dysplasia), and, therefore, the number of patients in any particular group (e.g., ASCUS women who had topical treatment only) was of necessity small. Therefore, it was not generally possible to conduct statistical analysis for all conditions and all interventions. However, overall, the response to therapy was reportedly favorable. A large proportion (74% [20/27]) of the women who received topical poly E ointment responded to therapy. This response is similar to the combination group and the oral treatment only group (75% [6/8] and 60% [6/10], respectively). The overall response to any form of green tea extract was 69% (35/51 patients). None of the treatment regimens appeared to be more effective than the others and the proprietary product was not clearly better than the other ECGC capsule. Green tea extract treatment did not consistently change HPV status. Extracts generally were well-tolerated. There was only a single case of increased liver function tests which resolved without withdrawal of medication. Very few symptoms were reported with topical use of poly E cream as well.
The main limitation in this study was the complexity of the design, which did not allow for a sufficient number of subjects in any arm of the study to demonstrate differences among therapy or for any given degree of dysplasia. However, the consistent response to all forms of green tea extract intervention was very encouraging. Although ointment was helpful, oral therapy in this study at least, appeared to be as effective, thus decreasing cost of administration and improving compliance with this potentially effective therapy.
Given the outcome of this trial (good response, low toxicity) together with the extensive experimental information available about the chemopreventative effects of green tea, we should consider recommending an 8-12 week trial of a high polyphenol content green tea extract at a dose of 200 mg/d for patients who present with cervical atypia—especially those patients for whom watchful waiting is the recommended conventional course of therapy. This also may be a reasonable supplement to consider using chronically for those patients at high risk of developing aggressive cervical carcinoma, and for HIV-positive and immunocompromised women. Green tea certainly bears further investigation as a primary preventive agent for cervical carcinoma.
Dr. Hardy, Associate Director, UCLA Center for Dietary Supplement Research: Botanicals Medical Director, Cedars-Sinai Integrative Medicine Program Los Angeles CA, is on the Editorial Advisory Baord of Alternative Therapies in Women’s Health.
1. Yang CS, et al. Tea and tea polyphenols in cancer prevention. J Nutr 2000;130(2S Suppl):472S-478S.
2. Arts IC, et al. Dietary catechins and cancer incidence among postmenopausal women: The Iowa Women’s Health Study (United States). Cancer Causes Control 2002;13:373-382.
3. Zhang M, et al. Tea consumption and ovarian cancer risk: A case-control study in China. Cancer Epidemiol Biomarkers Prev 2002;11:713-718.
4. Nakachi K, et al. Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn J Cancer Res 1998;89:254-261.
5. American Cancer Society. Cancer Prevention and Early Detection Facts and Figures; 2004.
6. World Health Organization. Disease burden of human papilloma virus. Available at: www.who.org. Accessed June 11, 2004.
7. Ahn WS, et al. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur J Cancer Prev 2003;12:383-390.