Shu-Lin Chuang, PhD1; Sam Li-Sheng Chen, PhD2 ; Amy Ming-Fang Yen, PhD2; Jean Ching-Yuan Fann, PhD3; Sherry Yueh-Hsia Chiu, PhD4; Chiu-Wen Su, PhD5; Hsiu-Hsi Chen, PhD1 1. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan 2. School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan 3. Department and Graduate Institute of Health Care Management, Kainan University, Tao-Yuan, Taiwan 4. Department and Graduate Institute of Health Care Management, Chang Gung University, Tao-Yuan, Taiwan 5. Department of Otolaryngology -Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan Applying Evidence of Translational Medicine to the Risk-Oriented Cancer Screening for Oral Neoplasm FREE OF ORAL CANCER ERYTHROLEUKOPLAKIA BETEL QUID CHEWING LEUKOPLAKIA ORAL CANCER CIGARETTE SMOKING PAI-1 – 675 hOGG1 codon 326 ACE intron 16 TIMP-2 – 418 miR-137 p53

Introduction and Objective: 　　Since the dose-response effect of betel quid chewing and cigarette smoking on multistate progression between oral pre-malignancy and oral cancer has been elucidated and in addition, there are quite amount of researches emphasizing on genetic and epigenetic effect on the risk of oral squamous-cell carcinoma, we would like to combine those evidences mentioned earlier and computer stimulation to construct the risk stratified profile for individuals based on the evidence of translation medicine. Methods: 　　We developed a risk assessment model on the ground of evidence from literature to incorporate important risk factors like betel quid chewing and cigarette smoking as well as genetic and epigenetic factors. A computer simulation was further applied to cohort with distribution of risk profiles the same as a high-risk group for oral screening in Taipei. We examined the results of screening program with different inter-screening interval combined, or not, with health education program for quitting betel quid chewing and cigarette smoking as attending the screening program to project the effectiveness when compared to a non-intervention control scenario. We simulated a hypothetical cohort of different inter-screening intervals combined with or without health education for quitting betel quid chewing and cigarette smoking. Applying Evidence of Translational Medicine to the Risk-Oriented Cancer Screening for Oral Neoplasm Shu-Lin Chuang, PhD1; Sam Li-Sheng Chen, PhD2 ; Amy Ming-Fang Yen, PhD2; Jean Ching-Yuan Fann, PhD3; Sherry Yueh-Hsia Chiu, PhD4; Chiu-Wen Su, PhD5; Hsiu-Hsi Chen, PhD1 1. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan 2. School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan 3. Department and Graduate Institute of Health Care Management, Kainan University, Tao-Yuan, Taiwan 4. Department and Graduate Institute of Health Care Management, Chang Gung University, Tao-Yuan, Taiwan 5. Department of Otolaryngology -Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan

MST of from ELP to OC (year) ACE intron 16 P53 TIMP-2 – 418 G/G vs. C/C and G/C: OR=26.33 (95% CI: 12.39-55.95) Vairaktaris et al, Oral Oncology, 2009 Positive vs. Negative: OR=17.05 (95% CI: 3.32-87.61) Chang et al, J Oral Pathol Med 2000 I/I vs. D/I or D/D: OR=9.16 (95% CI:1.14-73.50) hOGG1 codon 326 miR-137 PAI-1 – 675 4G/4G vs. 5G/4G or 5G/5G: OR=5.00 (95% CI: 1.32-8.92) Vairaktaris et al, Oral Oncology, 2009 SCCHN vs. Control: OR=4.80 (95% CI: 1.23-18.82) Langevin et al, Carcinogenesis 2010, CG/GG vs . CC: OR=1.42 (95% CI: 1.08-1.89) Tsou et al, Anticancer Research, 2010 Decile Lifetime Risk (per 105) RR MST of from ELP to OC (year) 1st 278 0.16 33.96 2nd 551 0.33 31.13 3rd 611 0.36 29.68 4th 628 0.37 14.88 5th 1,692 1.00 18.62 6th 1,937 1.14 10.65 7th 2,148 1.27 8.23 8th 4,327 2.56 7.68 9th 7,283 4.30 5.10 10th 9,992 5.91 1.03 Applying Evidence of Translational Medicine to the Risk-Oriented Cancer Screening for Oral Neoplasm Shu-Lin Chuang, PhD1; Sam Li-Sheng Chen, PhD2 ; Amy Ming-Fang Yen, PhD2; Jean Ching-Yuan Fann, PhD3; Sherry Yueh-Hsia Chiu, PhD4; Chiu-Wen Su, PhD5; Hsiu-Hsi Chen, PhD1 1. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan 2. School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan 3. Department and Graduate Institute of Health Care Management, Kainan University, Tao-Yuan, Taiwan 4. Department and Graduate Institute of Health Care Management, Chang Gung University, Tao-Yuan, Taiwan 5. Department of Otolaryngology -Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan

Target Population Demographic Feature (Age sex) Competing Risks of Death Individual Characteristic (EX. BETEL QUID CHEWING, CIGARETTE SMOKING) Screening Policy Simulated Cycle (year=0) FREE OF ORAL CANCER ERYTHROLEUKOPL -AKIA LEUKOPLAKIA ORAL CANCER Simulated Cycle (year+1) Intervention & Treatment YES Death ? Exit NO YES NO Normal ? Applying Evidence of Translational Medicine to the Risk-Oriented Cancer Screening for Oral Neoplasm Shu-Lin Chuang, PhD1; Sam Li-Sheng Chen, PhD2 ; Amy Ming-Fang Yen, PhD2; Jean Ching-Yuan Fann, PhD3; Sherry Yueh-Hsia Chiu, PhD4; Chiu-Wen Su, PhD5; Hsiu-Hsi Chen, PhD1 1. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan 2. School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan 3. Department and Graduate Institute of Health Care Management, Kainan University, Tao-Yuan, Taiwan 4. Department and Graduate Institute of Health Care Management, Chang Gung University, Tao-Yuan, Taiwan 5. Department of Otolaryngology -Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan

Conclusions: 　　We developed a risk assessment model to stratify the risk of oral squamous-cell carcinoma for all age cohort considering unhealthy oral habits like betel quid chewing and cigarette smoking, genetic and epigenetic factors in a multistate progression model to demonstrate how different prevention programs has varying effectiveness across different risk groups. Screening for Oral Neoplasma + Health Education Screening for Oral Neoplasma Applying Evidence of Translational Medicine to the Risk-Oriented Cancer Screening for Oral Neoplasm Shu-Lin Chuang, PhD1; Sam Li-Sheng Chen, PhD2 ; Amy Ming-Fang Yen, PhD2; Jean Ching-Yuan Fann, PhD3; Sherry Yueh-Hsia Chiu, PhD4; Chiu-Wen Su, PhD5; Hsiu-Hsi Chen, PhD1 1. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan 2. School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan 3. Department and Graduate Institute of Health Care Management, Kainan University, Tao-Yuan, Taiwan 4. Department and Graduate Institute of Health Care Management, Chang Gung University, Tao-Yuan, Taiwan 5. Department of Otolaryngology -Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan