Table 1. Criteria of Individual studies.

Study	Date published	Design	Inclusion	Exclusion	Overview of cases and controls	Number of Cases	Characteristics of the cases	Number of Controls	Characteristics of the controls	Study quality score	Comment
Moritz	1990	Case control Prospective	Patients with head and neck tumour that were either newly diagnosed or advanced	Ulceration or other factors leading to poor visualisation of carotids	Cases had prior radiation with or without surgical resection. Controls had head and neck tumours with no prior radiation. Some controls had prior surgery and some were newly diagnosed cases of head and neck tumour.	53	Average age 62 years. 45/53 were smokers. All had advanced head and neck cancers, mostly squamous, mostly treated with surgery and adjuvant radiation. Cases received a minimum of 50Gy and some received a boost of 10 to 20 Gy.	38	Average age 58 years. 35/38 were smokers. Most were newly diagnosed head and neck tumours.	10/27	Controls were mostly newly diagnosed head and neck tumour patients whereas cases already had undergone head and neck cancer management. The groups were similar in terms of smoking status and age. Data were absent regarding on other baseline characteristics. lesions exhibiting less than 50% cross-sectional stenosis were defined as "normal or mild"; those with multifocal involvement or 50% to 75% bilateral stenosis were classified as "moderate"; and those involving extensive areas, stenosis of greater than 75% luminal area on one side, or ulceration were classified as "severe."
Cheng	1998	Case control Prospective	NPC with prior radiation treatment with or without surgery.	Prior carotid surgery	Cases were patients who had undergone radiation for NPC for at least 12 months. Controls were "consecutive healthy individuals" who had undergone carotid scanning. No further details were provided on the source of controls.	96	All had 64–72Gy at the site of the primary and 45–66Gy to the neck. 28/91 were smokers. Mean age was 53.6 years.54/96 had undergone previous surgery. 75/96 were men.	96	Controls were "healthy" but no further details were provided. Mean age in controls was 61.8 years. 58/96 were male.	11/27	Controls were "healthy" patients and were on average older than cases. No other details were provided on important baseline characteristics. It is likely that cases had more cardiovascular risk factors as cases had cancer and controls were "healthy" .Carotid stenosis was defined as mild (0%–29%), moderate (30%–69%), severe (70%–99%), and totally occlusive. Stenosis of 70% or greater was regarded as significant.
Carmody	1999	Case control Retrospective	Men who underwent carotid scanning within a defined 6 year period from 1993 to 1998.	None specified	Cases were patients who had received high dose radiation for head and neck cancer within the prior 12 years and who had undergone a carotid duplex scan between 1993 and 1998. Randomly selected age–matched patients who had received carotid duplex scans were chosen as controls. None of the controls had prior neck radiation.	23	Mean radiation dose was 6060+/−182 rads. Mean age was 67.8 years. 23/23 were smokers. 12/23 had coronary artery disease, 18/23 had hypertension, 1/23 had hypercholesterolaemia, 9/23 had diabetes, 9/23 had a previous stroke and 5/23 had peripheral vascular disease.	46	Mean age was 68.3 years. 43/46 were smokers. 23/46 had coronary artery disease, 35/46 had hypertension, 9/46 had hypercholesterolaemia, 19/46 had diabetes, 15/46 had a previous stroke and 14/46 had peripheral vascular disease.	16/27	Controls were randomly selected patients who had undergone carotid scanning. Cases and controls were similar in terms of important baseline characteristics: mean age, smoking status and prevalence of coronary artery disease, hypertension, hypercholesterolaemia, diabetes, previous stroke and peripheral arterial disease were similar in cases and controls. Plaques associated with less than 40% cross-sectional stenosis were characterized as normal to mild; those exhibiting stenosis ranging from 40% to 70% were classified as moderate; and lesions resulting in 70% to 99% stenosis were characterized as severe. Vessels exhibiting lack of blood flow were designated as occluded
King	1999	Case control Prospective	Survivors of childhood or early adult lymphoma	None specified	Cases were survivors of childhood or early adult Hodgkin's lymphoma who had undergone radiation therapy at least 5 years prior to inclusion. Cases were all in remission and had no previous stroke or TIA. Controls were healthy volunteers. No further details were provided on the source of controls. Cases and controls underwent carotid duplex scanning.	42	Radiation doses varied from 2,250 to 4000 cGy. Mean age was 27 years. Mean number of pack years of smoking history was 20. 26/42 were males. 2/42 had a family history of cardiovascular or cerebrovascular disease.	33	Healthy volunteer controls. Mean age was 29 years. Mean number of pack years of smoking history was 32. 19/33 were males. 2/33 had a family history of cardiovascular or cerebrovascular disease.	16/27	Controls were "healthy volunteers". The source of controls was not described. Cases and controls were similar in terms of mean age, proportion with male gender, mean pack years of smoking history, prevalence of diabetes and regarding family history of cardiovascular or cerebrovascular disease. BMI values and lipid profiles were also similar. Other cardiovascular risk factors were not mentioned. Severe stenosis was defined as 70% or more on US
Lam Head and Neck	2001	Case control Prospective	Patients with NPC who had undergone neck radiation therapy for more than 3 years.	Patients who had hyperfractionated radiation therapy were excluded as were patients with recurrent NPC.	Cases were patients with NPC who had received neck radiotherapy 4–26 years prior. Controls were patients who were newly diagnosed with NPC and who had never received radiation. Cases and controls underwent carotid duplex scanning.	80	Mean radiation dose to bilateral carotids was 56.6 Gy. Age range on was 38–69 years. 20/80 were smokers. 58/80 were male. 1/80 had hyperlipidaemia.	58	20/58 were smokers. 1/58 had hyperlipidaemia. No data were provided regarding other characteristics of controls.	8/27	Cases and controls were sourced from the same dedicated NPC clinic. Numbers of smokers and prevalence of hyperlipidaemia were similar in cases and controls but no data were provided on other important baseline cardiovascular risk factors. The percent reduction in diameter of the true lumen was used to define the degree of stenosis.
Lam Cancer	2001	Case control Prospective	Patients with a history of NPC and who were in remission following neck radiotherapy 4–20 years before inclusion in the study.	None specified	Cases were NPC patients who had been treated with radiation 4–20 years previously and we were in remission. Controls were newly diagnosed NPC patients. Cases and controls underwent carotid duplex scanning.	71	Median radiation dose to the carotids was 56.4 Gy. Mean age 53.6 years. 53/71 were males. 18/71 were smokers, 16/66 who had fasting lipid profile measurement had hypercholesterolaemia and 11/64 with fasting blood glucose measurement had hyperglycaemia.	51	Mean age 48.8 years. 35/51 males. 19/51 were smokers, 5/50 who had fasting lipid profile measurement had hypercholesterolaemia and 3/50 with fasting blood glucose measurement had hyperglycaemia.	11/27	Cases were significantly older than controls. The groups were similar in terms of gender, smoking status and the prevalence of dyslipidaemia and fasting hyperglycaemia but other cardiovascular risk factors were not described. Significant stenosis was diagnosed when there was greater than 50% reduction in luminal diameter
Chang	2009	Case control Prospective	Consecutive head and neck cancer patients under follow up by radiation oncology team from March 2002 to August 2006.	Patient with a previous stroke were excluded.	Cases were patients with remission of head and neck cancer after a course of radiation therapy. Controls were head and neck cancer patients who had carotid duplex scanning before radiation therapy commenced.	192	A total median value of 7060 cGy to the initial area of gross disease. All upper neck areas received at least 6000 cGy. Mean age was 49.9 years 139/192 male, 52/192 smokers, 18/192 had hypertension, 17/192 had diabetes, 8/192 had heart disease, 73/192 had dyslipidaemia.	98	Mean age was 49.8 years. 71/98 male, 30/98 smokers, 10/98 had hypertension, 11/98 had diabetes, 2/98 had heart disease, 30/98 had hyperlipidaemia.	17/27	The groups were similar regarding mean age, smoking status and the prevalence of hypertension, diabetes and hyperlipidaemia. 3 patients who had strokes were excluded - this is unlikely to have influenced results. Significant stenosis was defined as maximum stenosis ≥ 50%.
Greco	2012	Case control Prospective	Patients with head and neck tumours who were under follow up between January 2006 and February 2011.	Primary tumour recurrence, second primary tumours, death before 36 months after surgery, carotid stenosis of 50%+ at baseline, monolateral laterocervical irradiation.	Cases were head and neck cancer patients who had surgical treatment and adjuvant radiation. Controls were head and neck cancer patients who received surgery only. Cases and controls had carotid duplex scans 1 week and 36 months after surgery. Results at 36 months were used in this review.	39	Total radiation dose varied from 50 to 60 Gy. Mean age was 62.1 years, 31/39 were males, 31/39 were smokers, 8/39 had diabetes, 11/39 had hypertension, 6/39 had hyperlipidaemia.	54	Mean age 63.7 years, 31/54 males, 47/54 were smokers, 11/54 had diabetes, 12/54 had hypertension, 6/54 had hypercholesterolaemia.	15/27	The groups were similar in terms of mean age, gender, smoking status and tumour site. The prevalence of diabetes, hypertension and hyperlipidaemia were similar also. Carotid obstruction was classified as low (0–30%), moderate (31–49%) or severe (≥ 50%)