Table 1.

Characteristics of the population studied.

Study	Patients (N)	Tobacco Habits	Alcohol Habits	HPV/EBV Status	Age (Years)	Sex (M/F)	Comorbidities
Becker et al., 2014 [16]	Cases: 2874 HNC Diabetes: 214 HNC Diabetes Met−: 103 HNC Diabetes Met+: 111 1–29 prescriptions: 61 ≥30 prescriptions: 50 HNC Diabetes Ctrl: 17,244 Ctrl Diabetes: 1273 HNC HNC Diabetes Met−: 560 HNC Diabetes Met+: 713 1–29 prescriptions: 392 ≥30 prescriptions: 321	HNC: Non-smoker: 835 Current: 973 Past: 720 Unknown: 346 Ctrl: Non-smoker: 7583 Current: 3135 Past: 4704 Unknown: 1822	HNC: Never: 384 Current: 1993 Past: 59 Unknown: 438 Ctrl: Never: 2582 Current: 11,954 Past: 225 Unknown: 2483	/	HNC <40: 160 40–59: 1011 60–69: 771 70–79: 652 80–89: 280 Ctrl: <40: 900 40–59: 5944 60–69: 4601 70–79: 4008 80–89: 1791	HNC: M: 1834 F: 1040 Ctrl: M: 11,004 F: 6240	HNC CHF: 73 IHD: 312 Hypertension: 851 Stroke/TIA: 164 Dyslipidaemia: 300 Diabetes: 216 EBV: 10 Asbestosis: 12 Ctrl: CHF: 405 IHD: 1928 Hypertension: 5173 Stroke/TIA: 900 Dyslipidaemia: 1939 DM: 1343 EBV: 86 Asbestosis: 46
Tseng 2016 [17]	Original sample: Met+: 288,198 Oral cancer: 1273 Met−: 16,263 Oral cancer: 119 Matched sample: Met+: 16,263 Met−: 16,263	Original sample Met+: Smoker: 5915 Non-smoker: 282,283 Met−: smoker: 266 Non-smoker: 15,997 Matched sample Met+: smoker: 247 Non-smoker: 16,016 Met−: Smoker: 266 Non-smoker: 15,997	Original sample Met+: Abuser: 15,451 Non-abuser: 272,747 Met−: Abuser: 1037 Non-abuser: 15,226 Matched sample Met+: Abuser: 1059 Non-abuser: 15,204 Met−: Abuser: 1037 Non-abuser: 15,226	/	Original sample: Met+: 56.6 (+/−10.2) Met−: 59.1 (+/−10.4) Matched sample: Met+: 59.4 (+/−9.7) Met−: 59.1 (+/−10.2)	Original sample: Met+: M: 155,199 F: 132,999 Met−: M: 9332 F: 6931 Matched sample: Met+: M: 9437 F: 6826 Met−: M: 9332 F: 6931	Original sample Met+: Hypertension: 198,483 Dyslipidaemia: 197,488 COPD: 110,809 Diabetes-related complications: Nephropathy: 46,223 Eye disease: 41,653 Stroke: 54,814 IHD: 98,033 PAD: 45,915 Met−: Hypertension: 11,995 Dyslipidaemia: 9855 COPD: 6521 Diabetes-related complications: Nephropathy: 4139 Eye disease: 1529 Stroke: 4021 IHD: 6218 PAD: 2516 Matched sample Met+: Hypertension: 12,033 Dyslipidaemia: 9690 COPD: 6509 Diabetes-related complications: Nephropathy: 4123 Eye disease: 1341 Stroke: 3947 IHD: 6256 PAD: 2505 Met−: Hypertension: 11,995 Dyslipidaemia: 9855 COPD: 6521 Diabetes-related complications: Nephropathy: 4139 Eye disease: 1529 Stroke: 4021 IHD: 6218 PAD: 2516
Tseng 2018 [18]	Met+: 15,486 Met−: 15,486	/	/	/	Met+: <50: 1415 >50: 14,071 Met−: <50: 1654 >50: 13,832	Met+: M: 8898 F:6588 Met− M: 8953 F: 6533	Met+ Nephropathy: 4840 Liver disease: 3288 Oesophagus, stomach, duodenum diseases: 13,361 Met−: Nephropathy: 4910 Liver disease: 3357 Oesophagus, stomach, duodenum diseases: 13,340
Yen et al., 2014 [3] *	Diabetic Met + 33,300 Diabetic Met − 33,300	/	/	/	Met+: <40:4452 40–65: 18,321 >65: 10,527 Met−: <40:4452 40–65: 18,321 >65: 10,527	Met+: F: 16,287 M: 17,013 Met−: F: 16,287 M: 17,013	Met+: Coronary artery disease: 2507 Obesity: 65 CKD: 555 Hyperlipidaemia: 1388 Hypertension: 8663 Met−: Coronary artery disease: 2507 Obesity: 65 CKD: 555 Hyperlipidaemia: 1388 Hypertension: 8663

* Yen et al., 2014, evaluated both the effect on the prognosis and the prevention of HNC and is described in Table 1. Abbreviations: CHF: Congestive heart failure; CKD: Chronic kidney disease COPD: Chronic obstructive pulmonary disease; Ctrl: control; EBV: Epstein–Barr virus infection; F: Female; HNC: Head and neck cancer; IHD: Ischaemic heart disease; M: Male Met−: not treated with metformin; Met+: treated with metformin; PAD: Peripheral arterial disease; TIA: Transient ischaemic attack.