Table 2.

Clinical studies on the use of trace elements in the treatment of cervical cancer

Study type/design of the study	Trial site	Samples and method of analysis	Name of trace element	No. of Subjects	Observed Values	Test and P-value	Outcome	Reference
Case-control study	Regional Institute of Medical sciences and hospital, Imphal, Manipur	Blood samples analyzed by Di-Br-PAESA method	Cu levels before and after the treatment (surgery, chemotherapy, radiotherapy or combined)	50 patients with a mean age of 57.78±17.66years comprising of 8 – Stage I, 13 – Stage II, 14 – Stage III, 15 – Stage IV and 30 Controls with a mean age of 57.74±12.12years	Control: 121.85±5.54μg/dl Patient: Before treatment 202.5±10.6μg/dl 215.5±9.63μg/dl 229.33±16.55μg/dl 237.5±15.85μg/dl After treatment 160.03μg/dl 165.85±10.6μg/dl 175.33±3.05μg/dl 180.62±11.55μg/dl	t-test	The results of this study concluded that the increased levels of serum copper in cervical cancer correlates with the cancer stages. This suggests that copper can be used as a parameter for cervical cancer screening, and can also be used as a valuable prognostic marker to monitor disease activity.	[144]
Case-control study	Dept of radiotherapy of a tertiary health care institute of central India	Blood samples and analyzed by Atomic absorption spectrophotometer	Zn levels in patients as compared with controls after pre and post-treatment with chemo-irradiation.	34 patients and 34 healthy controls with a mean age of 47.54 years	Pre-treatment Control – 0.34074ppm Patient – 0.31882ppm Post-treatment Group1- 0.34179ppm (Complete response CR) Group 2 – 0.32290ppm (Partial response PR/No response NR)	Unpaired t-test 0.0775 0.0463	The mean Zn serum value in patients with cervical cancer who received CTRT (Concurrent Chemoradiation Therapy) and achieved a complete response (CR) was significantly higher than that in patients with partial response (PR) / no response (NR). It points to the potential relation between mean serum zinc values and the patient's treatment outcome. Furthermore, they found no substantial difference between controls and patients in the serum Zn levels.	[138]
Case-control study	Sri Venkateswara Medical College, Tirupathi, India.	Blood samples analyzed by Atomic absorption spectrophotometric method	Selenium levels before and after treatment with chemotherapy and radiotherapies	104 Cervical cancer patients comprising of 54 treated with chemotherapy (age: 46.13±4 years) and 50 treated with radiotherapy, and 50 Controls (age: 30-73 years)	Before treatment Control: 13.83±0.21μg/dl Patients: 7.32±0.59μg/dl After treatment Chemotherapy: 11.16±0.32μg/dl Radiotherapy: 8.90±1.23μg/dl	t-test and ANOVA	The findings revealed that chemotherapy, but not radiotherapy, had increased the levels of trace elements and antioxidant activity in the blood serum of patients with cervical cancer. Increased Se in the serum of patients with cancer induces increased production of Se-dependent antioxidant mechanisms like GPx.	[145]
Randomized multicenter study	Freiburg, Germany	Whole-blood samples	Selenium supplementation for reducing the side effects of patients treated with radiotherapy (RT) for cervical and uterine cancer	80 Patients with a mean age of 64.3±10.1 years comprising of 70 with uterine cancer, 11 with cervical cancer -grouped as 39 selenium group (SG), 42 the control group (CG)	Before RT Se supplementation – 65.3μg/dl Without Se – 63.2μg/dl 50% RT Se supplementation – 93.2μg/dl Without Se – 67.3μg/dl End of RT Se supplementation – 90.9μg/dl Without Se – 61.4μg/dl 6 weeks after RT Se supplementation – 73.2μg/dl Without Se – 69.0μg/dl	t-test and Mann-Whitney U-test 0.49 <0.001 <0.001 0.32	During RT, selenium supplementation is effective in improving blood serum status in patients with Se-deficient cervical and uterine cancer and reduced the number of episodes and frequency of RT-induced diarrhea.	[173]
Case-control study	Institute of Gynaecology and Obstetrics, Ancona University, Italy	Blood samples analyzed by Atomic absorption spectroscopy	Zn Supplementation	22 patients with locally advanced squamous cervical carcinoma, and 12 Healthy controls For both groups age is ≤60 years	Active thymulin (ZnFTS) (log-2) Controls: 3.0±0.3 Patients: 1.5±0.5 Total thymulin (ZnFTS + FTS) (log-2) Controls: 4.5±0.3 Patients: 4.5±0.3 Zinc Controls: 112.4±16.1μg/dl-1 Patients: 100.7±9.3 μg/dl-1 α2-Macroglobulin Controls: 178.8±17.2 μg/dl-1 Patients: 260.0±72.8 μg/dl-1	Student's t-test and ANOVA (one-way)	Active thymulin (Zn-FTS) was reduced in patients affected by locally advanced cervical carcinoma, whereas total thymulin level (active thymulin Zn-FTS + inactive thymulin FTS) was in the normal range. In vitro addition of Zn to plasma samples containing (FTS), revealing the total amount of thymulin (active+inactive) in the circulation. It was concluded that the ratio of total thymulin to active thymulin is the thymulin fraction that is saturable by Zn ions and represents a useful marker of true Zn deficiency and, consequently, of peripheral Zn which may be low despite plasma Zn levels in the normal range.	[219]
Case-control study	Radiotherapy Clinic at Pt.B.D.Sharma PGIMS, Rohtak, Haryana, India.	Blood samples and method analyzed Atomic absorption spectrophotometer	Se	25 patients with mean age 50.3 years and 20 healthy subjects with the same mean age	Se Control: 120.57±13.45ppb/ml Patient: 97.4±16.0ppb/ml	t-test	The findings of the present study suggested that low Se serum concentrations in patients with uterine cervical carcinoma might be a contributing factor in cervical cancer development. Se supplementation can play an essential role in carcinogenic chemoprevention.	[220]