Meta_Analysis在肿瘤循证医学中的应用_英文

Chin J Clin Oncol (2008) 5: 1~9DOI 10.1007/s11805-008-0001-y

Application of Meta-Analysis in Evidence-Based OncologyXiaoping Lin

Qingsheng WangABSTRACT The Cochrane Collaboration is an international not-for-profit Tianjin Medical University Cancer Institute &

Hospital, Tianjin 300060, China.and independent organization, dedicated to providing up-to-date evidence-based information about the effects of healthcare in the form of systematic reviews. Meta-analysis is a statistical tool to prepare the systematic reviews. This paper briefly introduces the above terms and how to apply evidence-based oncology. Recent findings by using meta-analysis for cancers of the breast, lung, colon, liver, stomach and cervix uteri were reviewed in three cancer fields, viz., etiologic research, screening and therapy. KEYWORDS: evidence-based medicine, cancer, systematic

reviews; meta-analysis.

Correspondence to: Qingsheng Wang

E-mail: anti@Evidence-based medicine is a useful research method and brand new theory in medical science, which has developed since the 1970’s. At the present time, cancer is one of most harmful diseases impacting our health and life, so evidence-based oncology should be widely practiced by medical professionals who work on can-cer prevention or in clinical settings. Research on evidence-based medicine will produce specific systematic reviews and guidelines to provide the best medical practice. In research involving evi-dence-based medicine, meta-analysis is frequently used as a basic statistical tool.

Evidence-Based Medicine

Definition of evidence-based medicineEvidence-based medicine has been defined as “the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence-based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research[1].” More recently it has been described as the “integration of best research evidence with clinical expertise and patient values[2].” The 3 key phrases in this definition are, “best research evidence”, “clinical expertise” and “patient values”.

Evidence-based medicine and Cochrane Collabora-

tion[3,4]

Received December 17, 2007; accepted

January 20, 2008.

CJCO

E-mail:cocr@

Tel (Fax):86-22-2352 2919The Cochrane Collaboration is an international not-for-profit and independent organization, dedicated to making up-to-date, accu-rate information about the effects of healthcare readily available worldwide. It produces and disseminates systematic reviews of healthcare interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. The Cochrane Collaboration was founded in 1993. The major prod-uct of the Cochrane Collaboration is the Cochrane Database of Systematic Reviews which is published quarterly as part of the Cochrane Library. The Cochrane Library consists of a regularly

Chin J Clin Oncol (2008) 5: 1~9updated collection of evidence-based medicine da-tabases, including The Cochrane Database of Sys-tematic Reviews. The Cochrane Library interface is provided by Wiley InterScience. The Cochrane Li-brary collected 5,053 systematic reviews and 522,340 randomized controlled clinical trials. Among those, 373 systematic reviews and 28,743 trials in the field of oncology were collected up to November 2007[4]. Evidence-based medicine and meta-analy-sisof the breast, lung, colon, liver, stomach and cervix uteri were reviewed in three fields, viz., cancer etio-logic research, screening and therapy. The selection categories of publications in this review were based on up-to-date, new problems and inconsistent results obtained from different studies. EtiologyMeta-analysis is the quantitative assessment of the pooled results of multiple clinical trials. It is ideally suited for use in assessing results of trials which, in oncology in particular, are often under-powered to de-tect small differences in primary endpoints, let alone subgroup analyses. There are 3 levels of evidence when we look at evidence-based medicine. The first level, the highest level, is data from randomized controlled trials, or meta-analyses of randomized controlled trials. The second level is data from case control studies or co-hort studies, and the third level of evidence is from case studies or single case reports. Based on PubMed Medline searching, the publica-tions for researches on evidence-based oncology by using meta-analysis increased from 107 in 1997 to 372 in 2006.

Basic methods of meta-analysis[5]

Meta-analysis has become a clearly defined tech-nique, with reporting standards for both randomized controlled trials and observational studies. There is a clear order for proceeding with a meta-analysis beginning with selection of the subject fol-lowed by retrieval of primary studies, evaluation of study quality and selection of those studies to be used. Thereafter, an appropriate statistical model must be selected, and the studies evaluated for heterogene-ity (qualitative and quantitative). The actual meta-analysis is then performed, and finally the results are evaluated for reproducibility (sensitivity testing) to ensure that bias does not influence the result. There are a number of freeware programs for meta-analysis. RevMan (Review Manager) developed by the Cochrane Collaboration can be downloaded from /RevMan. Another freeware, EPIMETA developed by CDC/USA can be down-loaded from http://ftp.cdc.gov/pub/Software/epimeta.Evidence-Based Oncology for Breast Cancer

Recent findings by using meta-analysis for cancers Breast cancer, as one of the known hormone related cancers, is a common malignant female disease. In recent decades, the associations between genes and breast cancer have been studied. Chen, S. and G. Par-migiani[6] analyzed 10 studies with a meta-analysis method, and reported that the cumulative breast can-cer risks at age 70 years were 57% (95% confidence interval [CI]=47%~66%) for BRCA1 and 49% 95% CI=40%~57%) for BRCA2 mutation carriers. An-other BRCA gene related disease, ovary cancer risk of 40% (95% CI=35%~46%) for BRCA1 and 18% (95% CI=13%~23%) for BRCA2 mutation carri-ers. The authors concluded that the risk estimates for BRCA1 and BRCA2 mutation carriers can be used by counselors and clinicians. The association between diabetes mellitus and risk of breast cancer has been summarized by Larsson, et al.[7] by using a random-effects model of meta-analysis including 20 studies (5 case-control and 15 cohort studies). All 20 studies showed that women with (versus without) diabetes had a statistically sig-nificant 20% increased risk of breast cancer (relative risk [RR], 1.20; 95% CI=1.12~1.28). The summary estimates were similar for case-control studies (RR, 1.18; 95% CI=1.05~1.32) and cohort studies (RR, 1.20; 95% CI=1.11~1.30). This meta-analysis indi-cates that diabetes is associated with an increased risk of breast cancer. It has being asked for decades whether oral contra-ceptives (OC) increase breast cancer risk. Kahlenborn et al.[8] performed a meta-analysis of case-control studies published after 1980, and examined the as-sociation between prior OC use and premenopausal breast cancer. Thirty-four studies were identified. Use of OCs was associated with an increased risk of pre-menopausal breast cancer in general (odds ratio [OR], 1.19; 95% CI=1.09~1.29) and across various patterns of OC use. OC use was associated with breast cancer risk in both parous (OR, 1.29; 95% CI=1.20~1.40) and nulliparous (OR, 1.24; 95% CI=0.92~1.67) wom-en. Use of OCs is associated with an increased risk of premenopausal breast cancer, especially with use before first full-term pregnancy in parous women. Green tea is another topic of great interest for the public as well as for medical professionals. Sun et al.[9] concluded that meta-analysis indicated a lower

Chin J Clin Oncol (2008) 5: 1~9

risk for breast cancer with green tea consumption, highest versus non/lowest intake (OR=0.78, 95% CI=0.61~0.98). Postmenopausal hormone therapy is widely used in developed countries and has become acceptable in China[10]. Shah et al.[10] reported results of a meta-anal-ysis of 13 studies including 700,000 patients. Post-menopausal estrogen therapy showed an increased OR of 1.16 (95% CI=1.06~1.28), with estimates for less than 5 years use, 1.16 (95% CI=1.02~1.32) and more than 5 years use, 1.20 (95% CI=1.06~1.37). Postmenopausal combined (estrogen-progestogen) hormone therapy resulted in an OR of 1.39 (95% CI=1.12~1.72), with estimates for less than 5 years use of 1.35 (95% CI=1.16, 1.57) and more than 5 years use, 1.63 (95% CI=1.22, 2.18). Megdal et al.[11] summarized that night work showed an increased breast cancer risk among women (RR, 1.51; 95% CI=1.36~1.68).

ScreeningHay et al.[12] conducted a meta-analysis of 12 prospec-tive studies that measured concern about breast can-cer at a baseline and subsequent breast self-examina-tion (BSE) or mammography utilization among 3,342 high-risk and general-population women. The meta-analysis supports the contention that breast cancer concern may motivate screening behavior, and that high levels of breast cancer concern are uncommon. Its finding is very important for behavior intervention research as well as to conduct breast cancer screen-ing. Benefits of screening mammography used for breast cancer have been analyzed by Hendrick, et al.[13] Meta-analysis including the most recent follow-up data from eight RCTs involving women aged 40~49 at entry demonstrates for the first time a sta-tistically significant 18% mortality reduction due to regular screening mammography in women of this age group. Unlike screening with mammography, breast self-examination (BSE) for early detection of breast cancer has produced significant results. Hackshaw and Paul[14] presented a meta-analysis of the effect of regular BSE on breast cancer mortality. There was no difference in the death rate in studies on women who detected their cancer during an examination (pooled RR 0.90, 95% CI=0.72~1.12). None of the trials of BSE training showed lower mortality, but showed more women seeking medical advice and having bi-opsies.

Therapyexpression and breast cancer has been widely investi-gated. De Laurentiis, et al.[15] reported a meta-analy-sis on the interaction between HER-2 expression and response to endocrine treatment in advanced breast cancer. The authors concluded that HER-2-positive metastatic breast cancer is less responsive to any type of endocrine treatment. This effect holds in the sub-group of patients with positive or unknown steroid receptors. Earlier detection of a breast cancer recurrence and metastases is important for patients with breast can-cer. Isasi, et al.[16] summarized the diagnostic perfor-mance of 18F-2-deoxy-2-fluoro-D-glucose-positron emission tomography (FDG-PET) in the evaluation of breast cancer recurrence and metastases. The pooled sensitivity was 90% (95% CI=86.8~93.2), and the pooled false positive rate was 11% (95% CI =7.8~14.6), after the exclusion of outliers. The maxi-mum combined sensitivity and specificity, was 88% (95% CI=86.0~90.6). FDG-PET is a valuable tool for detecting breast cancer recurrence and metastases. Mauri et al.[17] reported results of a meta-analysis and concluded that patients with breast cancer treated preoperatively with systemic therapy was apparently equivalent to those treated postoperatively with the same regimen in terms of survival and overall disease progression. Whelan et al.[18] conducted a meta-analysis includ-ing 18 trials (6,367 patients). Locoregional radiation after surgery in patients treated with systemic therapy was shown to reduce the risk of any recurrence (OR, 0.69; 95% CI=0.58~0.83), local recurrence (OR, 0.25; 95% CI=0.19~0.34), and mortality (OR, 0.83; 95% CI= 0.74~0.94). Evidence-Based Oncology for Lung CancerEtiologyHuman epidermal growth factor receptor-2 (HER-2) Except cigarette smoking, some other risk factors were analyzed recently by using meta-analysis. Based on 12 studies during 1990~2006, which de-tailed the relationship between lung cancer and the type of exposure, Mahjub and Sadri[19] reported that the OR of asbestos, cooking fuel, cooking fumes, motor and diesel exhaust related to lung cancer were 1.67, 1.99, 2.52 and 1.42 (P<0.001), respectively. The OR of metal fumes related to lung cancer was 1.28 (P<0.01). The combined OR for the environmental and occupational exposure related to lung cancer was 1.67 (P<0.001). Residential radon exposure is of serious public concern due to the fact that people stay in their rooms most of the time. Darby et al.[20] concluded that resi-

Chin J Clin Oncol (2008) 5: 1~9dential radon is a cause of lung cancer in the general population. The estimated risks at 0, 100, and 400 Bq/m3, relative to life-long nonsmokers, with no radon exposure, were 1.0, 1.2, and 1.6 for life-long nonsmokers, and 25.8, 29.9, and 42.3 for continuing smokers of 15~24 cigarettes/day. Taylor et al.[21] analyzed 43 primary studies from 1981 to the end of 1999. The abundance of evidence clearly indicated that non-smokers exposed to envi-ronmental tobacco smoke (ETS) are at increased risk for lung cancer. The pooled RR for never-smoking women exposed to ETS from spouses, compared with unexposed never-smoking women was 1.29 (95% CI=1.17~1.43).

Screeningchemotherapy and is currently the best estimate of the effectiveness of this therapy. Whether particular types of patients may benefit more or less from preopera-tive chemotherapy is unknown. A meta-analysis of phase III randomized trials as to whether chemotherapeutic combinations for advanced non-small cell lung cancer should use a platinum-based protocol, was made by Pujol et al.[27] A platinum-based doublet induced a statically sig-nificant reduction in the risk of death when compared with non-platinum chemotherapy without inducing an unacceptable increase in toxicity. Evidence-Based Oncology for Colon Cancer

EtiologyMany studies have examined different screening strategies for lung cancer. Through meta-analysis, Manser et al.[22] concluded that the current evidence does not support screening for lung cancer with chest radiography or sputum cytological examination. They suggested that frequent chest radiography might be harmful. Diederich et al.[23] reported that preliminary studies of low-dose CT in heavy smokers had demonstrated a high proportion of asymptomatic, early, resectable cancers with good survival, but some bias existed and there were no evidence of mortality reduction. Gen-eral recommendations to screen individuals at risk for lung cancer with low-dose CT should be made.

Therapy Based on 19 trials employing meta-analysis, Baggstrom et al.[24] concluded that third-generation chemotherapy agents (paclitaxel, docetaxel, gem-citabine, vinorelbine, and irinotecan) have achieved a significant advance in the treatment of non-small cell lung cancer (NSCLC) (12% survival difference versus second-generation (2G) platinum-based regi-mens). Pijls-Johannesma et al.[25] conducted a systematic review, and meta-analysis of randomized controlled trials on the timing of chest radiotherapy in patients with limited stage small cell lung cancer (LS-SCLC). When platinum-based chemotherapy concurrently with chest radiotherapy is used, the 2- and 5-year sur-vival rates of patients with LS-SCLC may be in favor of early chest radiotherapy, with a significant differ-ence if the overall treatment time of chest radiation is less than 30 days. Burdett et al.[26] investigated 12 eligible randomized controlled trials to look at outcome of chemotherapy and surgery versus surgery alone in NSCLC. This analysis showed a significant benefit of preoperative The association between dietary fruits/vegetables and cancer have been investigated in many studies. In a pooled analysis of 14 cohort studies, Koushik et al.[28] concluded that dietary fruit and vegetables were not strongly associated with colon-cancer risk overall, but may be associated with a lower risk of distal colon cancer (RR= 0.74, 95% CI=0.57~0.95, P=0.02). Gorham et al.[29] reported that the evidence to date suggests that daily intake of 1,000~2,000 IU/day of vitamin D could reduce the incidence of colorectal cancer with minimal risk (OR=0.49, P<0.0001, 95% CI=0.35~0.68). Larsson and Wolk[30] analyzed the pooled risk of meat consumption for colon cancer and identified 15 prospective studies on red meat (involving 7,367 cases) and 14 prospective studies on processed meat consumption (7,903 cases). The summary RRs of colorectal cancer for the highest vs. the lowest intake categories were 1.28 (95% CI=1.15~1.42) for red meat and 1.20 (95% CI=1.11~1.31) for processed meat. The meta-analysis supported the hypothesis that high consumption of red meat and of processed meat is associated with an increased risk of colorectal cancer. Larsson et al.[31] conducted a meta-analysis includ-ing 6 case-control and 9 cohort studies. The results support a relationship between diabetes and increased risk of colon and rectal cancer in both women and men (summary RR=1.26, 95% CI=1.05~1.50). Samad et al.[32] reported a meta-analysis including 19 cohort studies that showed considerable evidence that physical activity is associated with reduced risk of colon cancer in both males and females. ScreeningHeresbach et al.[33] reported that biennial fecal occult blood testing decreased colorectal cancer mortality by

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14% (RR= 0.86; 95% CI=0.79~0.94) when performed over 10 years. Rosman and Korsten[34] analyzed thirty studies in which meta-analysis of CT colonography was used. The results showed that CT colonography has a rea-sonable sensitivity and specificity for detecting large polyps, but was less accurate than endoscopic colo-noscopy for smaller polyps. Thus, CT colonography may not be a reasonable alternative in situations in which a small polyp may be clinically relevant. Therapy The benefits of early chemotherapy in asymptomatic metastatic colorectal cancer were analyzed by Ack-land et al.[35] There was no difference in overall qual-ity of life or its individual domains between the two treatment strategies (immediate or delayed treatment at onset of predefined symptoms) at baseline, or at any subsequent time point. Early treatment of asymp-tomatic patients with metastatic colorectal cancer did not provide a survival benefit or improved quality of life compared to withholding treatment until symp-toms occurred. Bonjer et al.[36] performed a meta-analysis of trials randomizing patients with colon cancer to laparoscop-ically assisted or open colectomy. They confirmed that laparoscopically assisted colectomy for cancer is safe. mortality in a meta-analysis. The meta-standardized mortality ratio for liver cancers other than angiosar-coma was 1.35 (95% CI=1.04~1.77). Shi et al.[40] analyzed 32 case-control studies in-volving 3,201 patients with liver cancer and 4,005 controls, identified from a computer-based literature search from 1966 to 2004 in China. The pooled OR for HBsAg (hepatitis B surface antigen) positiv-ity was 14.1 (95% CI=10.6~18.8); for anti-HCV (HCV=hepatitis C virus)/HCV RNA positivity was 4.6 (95% CI=3.6~5.9) and positivity for both HB-sAg and anti-HCV/HCV RNA was 35.7 (95% CI= 26.2~48.5). Hepatitis B virus and Hepatitis C virus infections are main independent risk factors and in China act as synergists for hepatocellular carcinoma (HCC) if both are positive. ScreeningDe Masi et al.[41] evaluated the benefits of screening for hepatocellular carcinoma. The available screen-ing tests to detect hepatocellular carcinoma are alpha-fetoprotein and ultrasound with reported sensitivity and specificity of 50~85% and 70~90%, respectively. Although screening for the early detection of hepa-tocellular carcinoma has become quite common in clinical practice, its effectiveness remains controver-sial due to possible lead-time bias.

Therapy

Evidence-Based Oncology for Liver Cancer

EtiologyOverweight and obesity have shown a weak associa-tion with liver cancer risk. Larsson and Wolk[37] used meta-analysis to analyze 11 cohort studies and found that if normal weight is employed as a reference group, the summary RRs of liver cancer were 1.17 (95% CI=1.02~1.34) for those who were overweight, and 1.89 (95% CI=1.51~2.36) for those who were obese. Excess body weight is associated with an in-creased risk of liver cancer. Based on a meta-analysis conducted by Larsson and Wolk[38] on 4 cohort and 5 case-control stud-ies, involving 2,260 cases and 239,146 controls, the results suggested that an increased consumption of coffee may reduce the risk of liver cancer. The sum-mary RRs of liver cancer for an increase in consump-tion of 2 cups of coffee per day were 0.56 (95% CI= 0.35~0.91) and 0.69 (95% CI=0.55~0.87) respec-tively for persons with or without a history of liver disease. Boffetta et al.[39] analyzed the association between occupational exposure to vinyl chloride and cancer There is no standard treatment for patients with un-resectable HCC. Llovet and Bruix[42] analyzed 14 randomized controlled trials assessing arterial embo-lization (7 trials, 545 patients) or tamoxifen (7 trials, 898 patients). Arterial embolization improved 2-year survival compared with the controls (OR=0.53; 95% CI=0.32~0.89; P=0.017). Sensitivity analysis showed a significant benefit of chemoembolization with cis-platin or doxorubicin (OR, 0.42; 95% CI=0.20~0.88), but none with embolization alone (OR, 0.59; 95% CI=0.29~1.20). Tamoxifen showed no antitumoral effect and no survival benefits (OR, 0.64; 95% CI=0.36~1.13; P=0.13). The authors conclude that chemoembolization improves survival of patients with unresectable HCC and may become the standard treatment. Laparoscopic surgery for hepatic neoplasms aims to provide curative resection while minimizing complications. In a meta-analysis, Simillis et al.[43] reported that laparoscopic resection results in re-duced operative blood loss and earlier recovery with oncologic clearance comparable with open surgery. When performed by experienced surgeons in selected patients, it may be a safe and feasible option. Although transarterial chemoembolization im-

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Screeningproves survival in patients with HCC, it is not known if transarterial chemoembolization combined with other treatments is beneficial. Marelli et al.[44] used the meta-analysis method and concluded that a combined approach involving transarterial chemoembolization and percutaneous ablation improves survival. Adju-vant transarterial injection of chemotherapeutic drugs mixed with lipiodol improves outcome after hepa-tectomy. Transarterial chemoembolization is useful to control a tumor burden while the patient is on a waiting list for orthotopic liver transplantation. Multi-modal treatment seems to be the best way to optimize transarterial chemoembolization outcomes in HCC. For the purpose assessing the validity of the measure-ment of pepsinogen I and II as a screening test for gastric cancer and pre-malignant lesions, namely low-grade dysplasia, both in the general population and in selected groups of patients, Dinis-Ribeiro et al.[49] pooled 42 data sets including 27 (64%) population-based screening studies (n=296,553) and 15 (36%) sets of selected individuals (n=4,385). A pepsinogen test definition should include the pepsinogen I/II ratio due to its consistent result. Further studies of this test in the management of high-risk patients seem to be worthwhile.

Therapy Evidence-Based Oncology for Stomach

Cancer

EtiologyLarsson et al.[45] analyzed the association between processed meat consumption and stomach cancer risk in a meta-analysis. Increased consumption of processed meat is associated with an increased risk of stomach cancer, but the possibility that the associa-tion may be confounded or modified by other factors cannot be ruled out. It has been suggested that consumption of soy foods may be associated with a reduction in risk of various cancers. Wu et al.[46] conducted a pooled analysis of 14 studies with data on eating fermented soy foods. They showed an OR/RR of 1.26 (95% CI=1.11~1.43) for stomach cancer in association with high intake of such foods. In contrast, the pooled analysis of 10 studies with data on non-fermented soy foods found an OR/RR of 0.72 (95% CI=0.63~0.82) in association with a high intake of these foods. How-ever, the authors reminded the readers that the results were not adjusted for salt, fruit and vegetable intake. Based on a meta-analysis conducted by Lunet et al.[47] fruit or vegetable intake was associated with a decreased risk of gastric cancer regardless of the ana-tomical location and the histological type, although dietary intake had a more clear-cut protective effect on intestinal-type cancers. Wang et al.[48] conducted a meta-analysis on the as-sociation between Helicobacter pylori infection and early gastric cancer (EGC). This study indicated that H. pylori infection is strongly associated with EGC when compared with non-neoplasm controls or ad-vanced gastric cancer. To determine more accurately the extent of H. pylori in EGC, age-matched normal controls or adjustment for age in the analysis should be considered in H. pylori-related gastric cancer case-control studies. Hosono et al.[50] analyzed short-term outcomes of 1,611 procedures from 4 randomized controlled trials and 12 retrospective studies after laparoscopy-assist-ed distal gastrectomy. Laparoscopy-assisted distal gastrectomy for early gastric cancer is associated with a lower morbidity, less pain, faster bowel function re-covery, and shorter hospital stay. Assessment of the efficacy and tolerability of che-motherapy in patients with advanced gastric cancer was studied in a systematic review by using meta-analysis by Wagner et al.[51] Best survival results are achieved with 3-drug regimens containing fluoro-uracil (FU), an anthracycline, and cisplatin. Among these, regimens including FU as a bolus exhibited a higher rate of toxic deaths than regimens using a con-tinuous infusion of FU, such as epirubicin, cisplatin, and continuous-infusion FU. Casaretto et al.[52] conducted a meta-analysis to compare the efficacy of chemotherapy and support treatment in patients with advanced non-resectable gastric cancer. Five studies fulfilled the inclusion criteria, for a total of 390 participants, 208 (53%) re-ceiving chemotherapy, 182 (47%) receiving support care treatment and 6 losses (1.6%). Chemotherapy increased the 1-year survival rate of the patients and provided a longer symptom-free period of 6 months and an improvement in quality of life. Evidence-Based Oncology for Cancer of the CervixEtiologyCastellsague, et al.[53] pooled data from 8 case-control studies of cervical cancer. A total of 167 cases with invasive cervical adenocarcinoma (112 with adeno-carcinoma and 55 with adenosquamous carcinoma) and 1,881 hospital-based control subjects were in-cluded. The adjusted overall OR for cervical adeno-

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carcinoma in human papillomavirus (HPV)-positive women compared with HPV-negative women was 81.3 (95% CI=42.0~157.1). HPV16 and HPV18 were present in 82% of the patients. HPV appears to be the key risk factor for cervical adenocarcinoma. HPV testing in primary screening using current mixtures of HPV types and HPV vaccination against main HPV types should reduce the incidence of this cancer worldwide. Appleby et al.[54] combined individual data on 13,541 women with and 23,017 women without cer-vical carcinoma, from 23 epidemiological studies. Smokers are at an increased risk of squamous cell (RR=1.95, 95% CI=1.43~2.65), but not of adenocar-cinoma (RR=1.95, 95% CI =1.43~2.65) of the cervix. The risk of squamous cell carcinoma increases in cur-rent smokers with the number of cigarettes smoked per day, and with a younger age at which smoking starts. Plummer et al.[55] reported that smoking in-creases the risk of cervical cancer among HPV posi-tive women.

ScreeningTherapyTzioras, et al.[59] analyzed 65 trials with survival data on 11,180 women to access the effects of different chemotherapy regimens on survival for advanced cervical cancer. The summary relative hazard was 1.02, (95% CI=0.84~1.24) for trials using neo-ad-juvant chemotherapy and 0.85 (95% CI=0.73~1.00) for trials using concurrent chemotherapy. Evidence on chemotherapy in women with advanced cervical cancer is not encouraging for major survival benefits. However, small benefits have been observed in some trials, especially with short-length cycles of cisplatin-based regimens and concurrent chemotherapy and radiotherapy. Current Problems and Future of Evidence-Based Oncology in ChinaOncology is the most updatable science in the medical fields, with the application of new theories, new techniques, new medicines and a huge budget. An incredible quantity of information in oncology and related fields in the changing world will be a terrible burden for medical professional oncologists. The Cochrane Collaboration, evidence-based medicine, systematic reviews and meta-analysis serve the needs of oncologists to catch up on those well-organized knowledge in order to provide the best medical service based on recent evidence for cancer prevention and treatment. Currently in China, there are 3 general problem areas in the development of evidence-based oncol-ogy. First, a lack of knowledge, attitude and a belief that evidence-based oncology will fit the situation for most oncologists in China. The second is a lack of national and international collaboration in evidence-based oncology and a lack of a well-organized pro-fessional team. The third problem area is the discon-nection between research and practice, between the statistician and clinician, and between scientists who conduct research and study the theory of evidence-based oncology and health authorities. To develop evidence-based medicine, a team of re-lated professionals should be established. To train oncologists and standardize clinical pro-cedure with the best evidence-based knowledge, the Chinese version of evidence-based guideline for cancer treatment, screening guideline for cancer early detection and oncology nursing guidelines should be developed. To help people for a healthy and longer life, a healthy life guideline should be developed by medical professionals in different fields including those who work on cancer prevention. Koliopoulos et al.[56] identified 25 studies fulfilling the inclusion criteria. The pooled sensitivity of Hybrid Capture 2(HC2), PCR, cytology [ASCUS (atypical cells of undetermined significance) or worse] and cy-tology [LSIL (low-grade squamous intraepithelial le-sion) or worse] was respectively 90%, 80.9%, 72.7% and 61.6%, and the pooled specificity was respective-ly 86.5%, 94.7%, 91.9% and 96.0%. The combination of HC2 and cytology had the highest sensitivity and lowest specificity, but there was no evidence to con-clude reduction of the incidence of or mortality from invasive cervical cancer among HPV-screened sub-jects compared to cytologically screened subjects. Cuzick et al.[57] summarized the studies on HPV testing in primary cervical cancer screening. HPV testing was substantially more sensitive in detecting CIN2+(moderate dysplasia) than cytology (96.1% vs. 53.0%), but less specific (90.7% vs. 96.3%). The results support the use of HPV testing as the sole primary screening test, with cytology reserved for women who test HPV positive. Bernstein et al.[58] pooled 25 studies to investigate a liquid-based cervical cytological smear study and conventional Papanicolaou smears comparing cyto-logical diagnosis and sample adequacy. The ThinPrep test improved sample adequacy, and led to improved diagnosis of low-grade and high-grade squamous in-traepithelial lesions. No difference was found in the rate of atypical cells of undetermined significance diagnosis between ThinPrep and conventional smear groups.

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