A.Nor ID age (years) Sex Smoking status Alcohol Diagnosis T N M Stage (early 1, advanced 2) Site Exact Site Total Follow-up Time (months) Recurrence Months until Recurrence New Cancer (in a new site) Months until New Cancer Death Months until Death Remarks

1 72 M Current Never scc 2 0 0 1 tongue left border of tongue 31 1 22 0 NA 1 31 22 months after resection, new cancer was found in neck lymph nodes2 64 M Current Current scc 2 0 0 1 floor of mouth left floor of mouth NA NA NA NA NA NA NA3 66 M Never Never scc 1 0 0 1 tongue left tougue 70 0 NA 0 NA 0 NA4 67 F Never Never scc 3 0 0 2 gingiva left lower gingiva (from left retromolar area to vestibular groove and to the floor of mouth inside) 30 NA NA NA NA 1 305 77 F Never Never scc 1 1 0 2 gingiva right oropharynx 69 0 NA NA NA 0 NA6 63 M Current Never scc 2 0 0 1 gingiva left lower gingiva (molar site) NA NA NA NA NA NA NA7 65 M Past Never scc 2 1 0 2 tongue left ventral tongue 65 1 12 0 NA 1 NA8 60 M Current Never scc 1 1 0 2 orapharynx left orapharynx 20 1 8 0 NA 1 209 64 M Current Current scc 3 1 0 2 gingiva left retromolar area NA NA NA NA NA 1 NA10 73 F Never Never scc 1 0 0 1 buccal left buccal mucosa 16 1 2 0 NA NA NA 2 months after resection, cancer recurred. The patient received second cancer resection. 13 months after second cancer resection, cancer recurred again11 70 F Never Never scc 2 0 0 1 gingiva left lower gingiva 21 1 10 1 21 0 NA 10 months after resection, enlargement of lymph nodes was found. 21 months after resection, new OSCC was found in left buccal and right lower lip12 67 M Never Current scc 4 1 0 2 gingiva left retromolar area 10 1 3 0 NA 1 1013 65 F Never Never scc 2 1 0 2 buccal left buccal mucosa 18 0 NA 1 10 1 1814 75 F Never Never scc 2 0 0 1 anterior palatine arch right anterior palatine arch 47 NA NA NA NA 1 4715 75 F Never Never scc 3 1 0 2 gingiva right lower gingiva (from 27 to retromolar area) 6 NA NA NA NA 1 616 81 M Past Current scc 3 1 0 2 gingiva left lower gingiva (tooth position 17 to 21) 56 0 NA 0 NA 0 NA17 69 M Current Current scc 2 1 0 2 tongue left border of tongue 5 1 4 0 NA 1 518 72 M Past Current scc 4 0 0 2 gingiva left lower gingiva (from median line to left retromolar area) 21 NA NA NA NA 1 2119 86 F Never Never scc 1 0 0 1 tongue left border of tongue 53 0 NA 0 NA 0 NA20 66 F Never Never scc 4 0 0 2 buccal left buccal mucosa 53 0 NA 0 NA 0 NA21 75 F Never Never scc 1 0 0 1 tongue right border of tongue NA NA NA NA NA NA NA22 28 F Never Never scc 3 0 0 2 tongue left tougue NA NA NA NA NA NA NA23 32 M Never Never scc 4 0 0 2 tongue right back of tougue 69 0 NA 0 NA 0 NA24 38 F Never NA scc 3 0 0 2 tongue right border of tongue 68 0 NA NA NA 0 NA25 36 M Current Never scc 3 1 0 2 gingiva left lower gingiva (tooth position 17 to 20) NA NA NA NA NA NA NA26 48 F Never Never scc 1 0 0 1 tongue left border of tongne 69 0 NA 0 NA 0 NA27 52 F Never Never scc 2 1 0 2 palate left palate (tooth position14&15) NA NA NA NA NA NA NA28 41 F Never Never scc 2 2 0 2 tongue&floor of mouth right tongue&floor of mouth 6 1 6 0 NA 1 629 44 M Current Current scc 3 1 0 2 tongue right ventral tongue 27 0 NA NA NA 0 NA30 49 M Current Current scc 1 0 0 1 tongue left ventral tongue&floor of mouth NA NA NA NA NA NA NA31 53 M Current Current scc 1 0 0 1 palate left palate (back of soft palate, near palatine arch) 18 0 NA 1 18 1 18 No recurrence for OSCC, died of esophageal carcinoma32 42 M Never Current scc 1 0 0 1 gingiva left border of tongue 64 0 NA NA NA 0 NA33 53 M Current Never scc 2 0 0 1 tongue left border of tongue 64 0 NA NA NA 0 NA 7 months later of OSCC sample collection, this patient received thyroid adenoma resection 34 56 F Current Current scc 2 0 0 1 buccal left buccal mucosa 63 0 NA 0 NA 0 NA35 50 M Current Current scc 2 0 0 1 tongue left ventral tongue 62 0 NA 0 NA 0 NA36 53 F Never Never scc 1 0 0 1 tongue left border of tongue 57 0 NA 0 NA 0 NA37 55 M Current Current scc 2 0 0 1 tongue left border of tongue 57 0 NA 0 NA 0 NA38 59 M Never Never scc 1 0 0 1 tongue right border of tongue 68 0 NA 0 NA 0 NA39 56 M Never Never scc 2 0 0 1 tongue left border of tongue NA NA NA NA NA NA NA40 53 M Current Current scc 3 0 0 2 floor of mouth left floor of mouth NA NA NA NA NA NA NA41 51 M Current Current scc x 0 0 1 floor of mouth left floor of mouth NA NA NA NA NA NA NA42 47 F Never Current scc 2 2 0 2 gingiva right lower gingiva (molar site) 62 0 NA 0 NA 0 NA43 47 M Never Never scc x 0 0 1 gingiva left upper gingiva (tooth position 13 14 15) NA NA NA NA NA NA NA44 47 F Never Never scc 3 1 0 2 tongue left border (back) of tongue 56 0 NA 0 NA 0 NA45 59 F Never Never scc 3 0 0 2 buccal left buccal mucosa 21 1 6 0 NA 1 2147 60 M Current Current scc 4 0 0 2 tongue left tongue NA NA NA NA NA NA NA48 58 F Never Current scc 3 0 0 2 tongue left border of tongue 56 0 NA 0 NA 0 NA49 57 F Never Never scc 2 0 0 1 gingiva right lower gingiva (molar site) 56 0 NA 0 NA 0 NA50 55 M Current Never scc 2 0 0 1 palate right hard palate 56 0 NA 0 NA 0 NA67 64 M Past Never scc NA NA NA NA NA left palate NA NA NA NA NA NA NA

M, masculine; F, feminine; scc, squamous cell carcinoma; NA, not available; 0, no; 1, yes.

B.Cancer (SCC) Normal control

9 15112 15235 15343 15436 15537 15644 15749 15848 15947 16014 16115 16216 16317 16418 16520 16621 16726 16839 16931 17033 17145 172

Cancer samples

Paired Samples

Supplemental Table 1

Nor ID age Sex Smoking status Alcohol Diagnosis Site51 37 M Past Never Normal gingiva52 46 F Never Never Normal gingiva53 48 M Never Never Normal gingiva54 55 F Never Never Normal gingiva55 35 F Never Never Normal gingiva56 47 M Current Never Normal gingiva57 34 M Current Never Normal gingiva58 37 F Never Never Normal gingiva59 36 F Never Never Normal gingiva60 52 M Current Never Normal gingiva61 42 M Current Never Normal gingiva62 48 F Never Never Normal gingiva63 32 F Never Never Normal gingiva64 34 M Never Never Normal gingiva65 45 F Never Never Normal NA66 63 F Never Never Normal gingiva68 56 M NA NA Normal gingiva69 60 M NA NA Normal gingiva70 51 F NA NA Normal gingiva71 65 M NA NA Normal floor of mouth72 81 F Past Current Normal gingiva73 58 F NA NA Normal gingiva74 54 F NA NA Normal gingiva75 74 F NA NA Normal NA76 45 M NA NA Normal gingiva77 48 F NA NA Normal gingiva78 50 M NA NA Normal gingiva79 73 F NA NA Normal buccal mucosa80 51 F NA NA Normal gingiva81 63 M NA NA Normal gingiva82 50 F NA NA Normal gingiva83 59 M NA NA Normal gingiva84 53 F NA NA Normal gingiva85 59 F NA NA Normal gingiva86 77 M NA NA Normal gingiva87 64 M NA NA Normal gingiva88 68 F Never NA Normal gingiva89 78 M Past NA Normal gingiva90 61 M Never NA Normal gingiva91 61 F Never NA Normal gingiva92 70 M NA NA Normal gingiva93 43 M Current NA Normal floor of mouth94 67 M Never NA Normal gingiva95 50 M Never NA Normal gingiva96 53 M Past NA Normal gingiva97 74 F Never NA Normal NA98 61 M Never NA Normal gingiva99 53 M Current NA Normal gingiva

100 59 F Never NA Normal gingivaM, masculine; F, feminine; NA, not available.

Normal samples

Supplemental Table 2

Nor ID age Sex Smoking status Alcohol Diagnosis Site Exact Site Total Follow-up Time Recurrence Months untill Recurrence New LK (in a new site) Months until New LK Cancerization (in the same site) Months until Cancerization Death Months untill Death Remarks135 71 M Past Never Mide dysplasia buccal right buccal mucosa 70 0 NA 0 NA 0 NA 0 NA136 68 M Past Never Mide dysplasia buccal right buccal mucosa 67 0 NA 0 NA 0 NA 0 NA137 62 F Current Never Mide dysplasia tongue left border of tongue NA NA NA NA NA NA NA NA NA138 64 M Current Never Mide dysplasia buccal left buccal mucosa 15 0 NA 0 NA 0 NA 1 15 Died of lung cancer139 64 F Never Never Mide dysplasia gingiva left lower gingiva 51 0 NA 0 NA 0 NA 0 NA140 72 M Never Never Mide dysplasia buccal left buccal mucosa 65 1 65 0 NA 0 NA 0 NA Recurrent homogeneous LK on the left buccal mucosa, size: 2.5mm*2mm141 62 M Current Current Mide dysplasia corner of mouth left corner of mouth 62 0 NA 0 NA 0 NA 0 NA142 65 M Current Never Mide dysplasia buccal left buccal mucosa 61 0 NA 0 NA 0 NA 0 NA143 40 M Past Current Mide dysplasia tongue dorsal tongue NA NA NA NA NA NA NA NA NA144 26 M Current Never Mide dysplasia tongue dorsal tongue NA NA NA NA NA NA NA NA NA145 47 M Current Never Mide dysplasia tongue right ventral tongue 63 0 NA 0 NA 0 NA 0 NA146 42 F Never Never Mide dysplasia buccal left buccal mucosa 62 0 NA 0 NA 0 NA 0 NA147 49 M Current Current Mide dysplasia lip lower lip NA NA NA NA NA NA NA NA NA148 39 M Current Current Mide dysplasia buccal left buccal mucosa NA NA NA NA NA NA NA NA NA149 51 F Never Never Mide dysplasia buccal left buccal mucosa NA NA NA NA NA NA NA NA NA150 52 M Never Never Mide dysplasia tongue right border of tongue 58 0 NA 0 NA 0 NA 0 NA46 56 F Never Never Moderate dysplasia tongue left ventral tongue 54 0 NA 0 NA NA NA 0 NA

118 73 F Never Never Moderate dysplasia tongue tongue 56 0 NA 0 NA 0 NA 0 NA119 75 F Never Current Moderate dysplasia gingiva left lower lingual gingiva 65 0 NA 0 NA 0 NA 0 NA120 74 F Never Never Moderate dysplasia tongue left border of tongue 130 1 128 1 128 1 115 0 NA121 72 F Never Never Moderate dysplasia tongue right ventral tongue 62 0 NA 0 NA 0 NA 0 NA122 53 F Never Never Moderate dysplasia tongue ventral tongue NA NA NA NA NA NA NA NA NA123 27 M Never Never Moderate dysplasia tongue right border of tongue NA NA NA NA NA NA NA NA NA124 50 M Past Never Moderate dysplasia buccal left buccal mucosa 54 0 NA 0 NA 0 NA 0 NA This patient also suffered oral lichen planus125 66 F Never Never Moderate dysplasia tongue left border of tongue NA NA NA NA NA NA NA NA NA126 63 M Never Current Moderate dysplasia tongue right ventral tongue 40 0 NA 0 NA 0 NA 0 NA127 61 M Current Past Moderate dysplasia buccal left buccal mucosa 21 0 NA 0 NA 0 NA 0 NA

128 74 F Never Never Moderate dysplasia buccal right buccal mucosa 20 0 NA 0 NA 0 NA 0 NALK lesions on both left and right buccal mucosal. The patient had experienced 2 pathological examinations for the right buccal mucosa LK,

with no recurrence, and 1 for the left, and is recurrent on 07-19-2013 clinical examination. The DNA was extracted from the right buccal tissue.

129 92 F Never Never Moderate dysplasia tongue left dorsal tongue 1 0 NA 0 NA 0 NA 0 NA130 56 F Never Never Moderate dysplasia gingiva right lower gingiva NA NA NA NA NA NA NA NA NA131 53 F Never Never Moderate dysplasia tongue right ventral tongue 49 0 NA 0 NA 0 NA 0 NA132 58 F Never Never Moderate dysplasia buccal right buccal mucosa 45 0 NA 0 NA 0 NA 0 NA133 54 F Never Never Moderate dysplasia tongue right dorsal tongue 28 NA NA NA NA NA NA 1 28 Died of HNSCC134 55 M Past Never Moderate dysplasia tongue left ventral tongue NA NA NA NA NA NA NA NA NA

102 62 M Past Never Severe dysplasia tongue right border of tongue 65 1 47 0 NA 0 NA 0 NA LK resection in March 2008. 02-15-2012 follow up: LK recurrence. 08-21-2013 Clinical Examination: LK recurrence, and received recurrent LK resection on 08-24-2013. Pathology: LK, moderate to severe dysplasia

103 66 M Current Current Severe dysplasia tongue right ventral tongue 53 0 NA 0 NA 0 NA 0 NA104 52 F Never Never Severe dysplasia NA NA NA NA NA NA NA NA NA NA NA105 46 F Never Never Severe dysplasia tongue right ventral tongue 63 0 NA 1 11 0 NA 0 NA106 65 M Never Never Severe dysplasia buccal left buccal mucosa 52 0 NA 0 NA 0 NA 0 NA107 65 M Never Never Severe dysplasia tongue left ventral tongue 49 1 49 0 NA 0 NA 0 NA108 68 M Never Never Severe dysplasia buccal left buccal mucosa 21 0 NA 0 NA 0 NA 0 NA109 43 F Never Current Severe dysplasia buccal left buccal mucosa 52 1 24 0 NA 0 NA 0 NA110 50 F Never Never Severe dysplasia tongue right border of tongue 47 0 NA 1 47 0 NA 0 NA New LK on the left tip of tongue and right lingual gingiva111 58 M Current Never Severe dysplasia tongue left ventral tongue 1 0 NA 0 NA 0 NA 0 NA112 57 M Never Never Severe dysplasia buccal left buccal mucosa 4 1 4 0 NA 0 NA 0 NA

M, masculine; F, feminine; NA, not available.

Dysplastic samples

Supplemental Table 3

Normal LK HNSCC P value54.7 58.1 58.2 >0.0551 51 54 >0.05

1 122 193 124 5x 20 351 132 2

M 0 / / 50 /Mi 16Mo 18Se 11

HNSCC-head and neck squamous cell carcinomaLK-leukoplakiaT-tumor; N-lymph node; M-metastasisDys-dysplasia Mi-mild dysplasiaMo-moderate dysplasiaSe-sevire dysplasia

SubjectsAge (years)Male (%)

T / / /

N / / /

Dys / / /

Supplemental Table 4