Cervical cancer is the fourth most common female cancer in terms of both incidence and mortality rates worldwide, with an estimated 528,000 new cases in 2012, including 266,000 deaths (85% occurring in developing countries) [1
]. Although screening methods and early detection programs have been established, invasive cervical cancer still represents a major concern for public health. Risk factors of cervical cancer include human papillomavirus (HPV), sexual behavior beginning at a young age (<16 years old), multiple sexual partners (more than four), history of genital warts, HIV positive, and cigarette smoking or environmental tobacco smoke [2
]. More than 99% of cervical cancer patients carry at least one genotype of oncogenic HPV [3
], since persistent infection with HPV is the prominent etiological reason in the formation of cervical cancer [4
]. However, more than 200 types of identified HPVs can be classified as low-risk HPVs and high-risk HPVs [5
]. Low-risk HPVs induce inconspicuous infection or benign papilloma which could eventually be resolved by the immune system and rarely cause neoplasia and carcinogenesis [6
]. On the contrary, high-risk HPVs are related to the propensity of malignant progression of virus-mediated lesions [7
]. Among them, HPV16 and HPV18 are the two major viruses responsible for approximately 70% of all cervical carcinomas worldwide. HPV has two vital transcriptional units, E6 and E7, that encoded oncoproteins primarily attribute to its oncogenic function [9
]. E6 protein inhibits the activity of tumor suppressor P53, and E7 protein targets other tumor suppressors of the retinoblastoma family [10
]. A series of human cervical cancer cell lines have been used to study the potential anticancer ability of chemo therapeutic agents, including HPV18-positive HeLa cell lines, HPV16-positive CaSki and SiHa cell lines, etc. Similar to other cancers, cervical cancer harms the human body mainly due to the proliferation and metastasis of cancer cells. Current treatments in curing cancers aim at anti-proliferation, anti-metastasis of cancer cells, and inducing cancer cell apoptosis.
Until now, prophylactic vaccination is the primarily effective prevention strategy for cervical malignancies [12
]. Although these vaccines could prevent approximately 90% of cervical carcinoma, the prohibitive price is incubus especially in developing countries [13
]. Besides prophylactic vaccination, cervical cancer remains curable if detected at early stage, but hard to remedy in metastatic or recurrent carcinoma [5
]. Among conventional therapies including surgery, radiotherapy, chemotherapy and immunotherapy [15
], chemotherapy is the first option for patients that could effectively promote the apoptosis of cancer cells. Nevertheless, due to its high chemoresistance ability and toxicity on normal cells, more effective methods using less toxic anticancer drugs and novel therapeutic intervention strategies are required nowadays. Polyphenols such as catechins, curcumin and ferulic acid with low side effects are potential safe anticancer strategies for cervical cancer intervention.
Tea is one of the three most widely consumed non-alcohol beverages in the world. The prominent catechins in teas are (-)-epigallocatechingallate (EGCG), (-)-epicatechingallate (ECG), (-)-epigallocatechin (EGC), and (-)-epicatechin (EC) [16
]. EGCG accounts for more than 40% of total catechins in green tea [17
], and plays a critical role in cancer chemoprevention, diabetes, neurodegenerative diseases, stroke, obesity and other biochemical disorders [18
]. The cancer prevention ability of EGCG is widely supported by results from epidemiological, in vivo and in vitro studies [19
], especially in breast cancer [23
], liver cancer [24
], and prostate cancer [25
]. However, the effects of EGCG on the prevention of cervical cancer are still inconclusive and controversial [27
]. This review summarizes recent research data mainly focused on the effects of EGCG on cervical cancer, including in vivo and in vitro studies, and offers directions for further study.