Prognostic Significance of Clinicopathological Factors Influencing Overall Survival and Event-Free Survival of Patients with Cervical Cancer: A Systematic Review and Meta-Analysis

Shengwei Kang; Junxiang Wu; Jie Li; Qing Hou; Bin Tang

doi:10.12659/MSM.934588

09 March 2022: Meta-Analysis

Prognostic Significance of Clinicopathological Factors Influencing Overall Survival and Event-Free Survival of Patients with Cervical Cancer: A Systematic Review and Meta-Analysis

Shengwei Kang ^12BDE , Junxiang Wu ^2C , Jie Li ^2F , Qing Hou ^1DEF , Bin Tang ^2AG*

DOI: 10.12659/MSM.934588

Med Sci Monit 2022; 28:e934588

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Table 2 Subgroup analysis for overall survival and event-free survival based on countries, FIGO stage, and cutoff value.

Prognostic factors	Outcome	Variables	Subgroups	HR and 95% CI	P value	I2 (%)	Q statistic	P value between subgroups
Age	OS	Countries	Eastern	1.11 (1.00–1.23)	0.052	61.8		0.703
		Countries	Western	1.08 (0.86–1.36)	0.489	72.0		0.703
		FIGO stage	I–II	1.23 (1.10–1.38)		56.2		0.070
			III–IV	1.13 (0.76–1.69)	0.539	0.0	0.719
			Both	0.94 (0.79–1.13)	0.524	72.7
		Cutoff value	≥50.0	1.09 (0.97–1.23)	0.162	68.2		0.592
		Cutoff value		1.13 (0.96–1.33)	0.140	58.4		0.592
		Study quality	High	1.03 (0.86–1.24)	0.723	71.9		0.206
		Study quality	Low	1.15 (1.03–1.28)	0.016	59.8		0.206
	EFS	Countries	Eastern	1.19 (1.02–1.38)	0.024	67.4		0.082
		Countries	Western	1.40 (0.99–1.98)	0.061	67.5	0.002	0.082
		FIGO stage	I–II	1.31 (1.13–1.52)		56.3
			III–IV	0.91 (0.59–1.40)	0.666	–	–
			Both	1.03 (0.76–1.39)	0.864	77.7
		Cutoff value	≥50.0	1.23 (1.04–1.46)	0.016	70.1		0.022
		Cutoff value		1.20 (0.96–1.51)	0.116	59.0	0.001	0.022
		Study quality	High	0.90 (0.76–1.08)	0.251	65.2
		Study quality	Low	1.49 (1.29–1.73)		37.6	0.019
Cell type	OS	Countries	Eastern	1.74 (1.52–1.98)		39.9	0.007	0.047
		Countries	Western	1.44 (1.20–1.73)		18.6	0.231	0.047
		FIGO stage	I–II	1.65 (1.43–1.91)		24.2	0.120	0.963
			III–IV	1.58 (0.89–2.78)	0.115	0.0	0.521
			Both	1.63 (1.36–1.95)		51.3	0.002
		Study quality	High	1.79 (1.53–2.09)		42.6	0.015	0.049
		Study quality	Low	1.50 (1.29–1.74)		26.5	0.090	0.049
	EFS	Countries	Eastern	1.68 (1.43–1.97)		62.9		0.008
		Countries	Western	1.50 (1.18–1.91)	0.001	58.8	0.001	0.008
		FIGO stage	I–II	1.56 (1.31–1.86)		65.2		0.490
			III–IV	2.33 (1.38–3.94)	0.002	–	–
			Both	1.71 (1.37–2.13)		59.8	0.001
		Study quality	High	1.88 (1.57–2.24)		67.4		0.004
		Study quality	Low	1.43 (1.17–1.74)		56.7		0.004
Depth of invasion	OS	Countries	Eastern	2.09 (1.66–2.63)		59.1		0.024
		Countries	Western	1.11 (0.52–2.38)	0.790	75.3	0.003	0.024
		FIGO stage	I–II	2.09 (1.65–2.63)		62.1		0.015
			III–IV	0.89 (0.42–1.89)	0.761	–	–
			Both	1.01 (0.43–2.37)	0.979	58.9	0.088
		Cutoff value	≥1/2	2.02 (1.59–2.57)		37.2	0.053	0.782
		Cutoff value		1.73 (1.15–2.61)	0.009	77.1		0.782
		Study quality	High	1.75 (1.20–2.55)	0.004	67.5	0.001	0.680
		Study quality	Low	2.02 (1.51–2.40)		62.6		0.680
	EFS	Countries	Eastern	1.83 (1.60–2.09)		28.1	0.070	0.010
		Countries	Western	1.29 (0.75–2.22)	0.359	80.7		0.010
		FIGO stage	I–II	1.77 (1.52–2.06)		51.6		0.054
			III–IV	0.93 (0.51–1.71)	0.815	–	–
			Both	0.86 (0.32–2.31)	0.765	–	–
		Cutoff value	≥1/2	1.67 (1.39–2.00)		43.8	0.019	0.549
		Cutoff value		1.77 (1.37–2.29)		60.5		0.549
		Study quality	High	1.64 (1.23–2.18)	0.001	69.1		0.596
		Study quality	Low	1.77 (1.49–2.09)		34.6	0.047	0.596
FIGO stage	OS	Countries	Eastern	1.86 (1.62–2.14)		84.1
		Countries	Western	2.36 (1.73–3.21)		85.9
		FIGO stage	I–II	1.60 (1.41–1.82)		73.4
			III–IV	1.47 (0.85–2.54)	0.168	–	–
			Both	2.51 (2.04–3.09)		81.7
		Cutoff value	IA or IB	1.92 (1.65–2.23)		87.6
		Cutoff value	II–III	2.24 (1.78–2.81)		64.9
		Study quality	High	2.40 (1.87–3.07)		86.9
		Study quality	Low	1.80 (1.57–2.06)		78.9
	EFS	Countries	Eastern	1.83 (1.60–2.08)		69.1		0.355
		Countries	Western	1.97 (1.61–2.41)		62.4		0.355
		FIGO stage	I–II	1.70 (1.50–1.93)		52.6		0.001
			III–IV	1.01 (0.55–1.83)	0.984	–	–
			Both	2.11 (1.75–2.54)		75.5
		Cutoff value	IA or IB	1.80 (1.59–2.04)		68.1		0.021
		Cutoff value	II–III	2.04 (1.65–2.52)		62.5		0.021
		Study quality	High	1.70 (1.45–2.00)		73.9		0.023
		Study quality	Low	1.99 (1.72–2.31)		61.3		0.023
Hemoglobin	OS	Countries	Eastern	1.56 (1.15–2.10)	0.004	58.1	0.019	0.001
		Countries	Western	3.05 (2.01–4.64)		0.0	0.608	0.001
		FIGO stage	I–II	1.39 (0.99–1.95)	0.061	0.0	0.898	0.720
			III–IV	1.81 (0.90–3.64)	0.097	-	-
			Both	2.07 (1.34–3.19)	0.001	75.7
		Cutoff value	10	1.94 (1.13–3.36)	0.017	80.2		0.156
		Cutoff value	>10	1.77 (1.39–2.27)		0.0	0.688	0.156
		Study quality	High	2.01 (1.00–4.04)	0.050	88.0		0.337
		Study quality	Low	1.70 (1.33–2.17)		0.0	0.740	0.337
	EFS	Countries	Eastern	1.20 (1.07–1.34)	0.002	4.3	0.401	0.004
		Countries	Western	2.25 (1.48–3.41)		0.0	0.580	0.004
		FIGO stage	I–II	1.58 (1.19–2.09)	0.001	0.0	0.778	0.071
			III–IV	–	–	–	–
			Both	1.24 (1.03–1.50)	0.022	53.6	0.044
		Cutoff value	10	1.50 (1.11–2.04)	0.009	58.9	0.023	0.248
		Cutoff value	>10	1.19 (1.04–1.35)	0.010	0.0	0.733	0.248
		Study quality	High	1.30 (0.86–1.96)	0.216	67.5	0.026	0.718
		Study quality	Low	1.29 (1.12–1.50)	0.001	18.5	0.284	0.718
Histological grade	OS	Countries	Eastern	1.56 (1.24–1.96)		56.3	0.004	0.460
		Countries	Western	1.48 (1.08–2.02)	0.014	55.0	0.011	0.460
		FIGO stage	I–II	1.44 (1.19–1.74)		41.6	0.030	0.414
			III–IV	–	–	–	–
			Both	1.75 (1.13–2.72)	0.012	72.6	0.001
		Cutoff value	1	1.52 (1.20–1.92)	0.001	61.8		0.424
		Cutoff value	2	1.56 (1.17–2.07)	0.002	32.6	0.157	0.424
		Study quality	High	1.43 (1.16–1.76)	0.001	29.1	0.160	0.839
		Study quality	Low	1.62 (1.20–2.19)	0.001	66.2		0.839
	EFS	Countries	Eastern	1.47 (1.09–1.97)	0.011	73.4		0.377
		Countries	Western	1.38 (1.07–1.78)	0.013	44.0	0.051	0.377
		FIGO stage	I–II	1.49 (1.17–1.89)	0.001	66.7		0.340
			III–IV	–	–	–	–
			Both	1.24 (0.99–1.57)	0.066	0.0	0.517
		Cutoff value	1	1.47 (1.13–1.90)	0.004	72.5		0.746
		Cutoff value	2	1.41 (1.15–1.73)	0.001	0.0	0.447	0.746
		Study quality	High	1.43 (1.12–1.84)	0.005	64.5	0.001	0.308
		Study quality	Low	1.45 (1.05–2.01)	0.025	58.7	0.013	0.308
Leukocytosis	OS	Countries	Eastern	2.20 (1.48–3.26)		75.2	0.001	0.726
		Countries	Western	2.46 (1.15–5.26)	0.020	-	-	0.726
		FIGO stage	I–II	1.55 (1.16–2.05)	0.003	0.0	0.623	0.013
			III–IV	3.04 (1.52–6.07)	0.002	-	-
			Both	2.66 (1.53–4.64)	0.001	73.7	0.010
		Cutoff value	≥10000	2.05 (1.25–3.35)	0.004	50.6	0.132	0.242
		Cutoff value		2.35 (1.39–4.00)	0.002	79.8	0.002	0.242
		Study quality	High	1.74 (1.18–2.56)	0.005	9.6	0.293	0.148
		Study quality	Low	2.41 (1.51–3.85)		76.6	0.002	0.148
	EFS	Countries	Eastern	2.08 (1.25–3.45)	0.005	69.6	0.011	–
		Countries	Western	–	–	–	–	–
		FIGO stage	I–II	1.66 (0.52–5.26)	0.389	–	–	0.642
			III–IV	–	–	–	–
			Both	2.14 (1.20–3.81)	0.010	76.8	0.005
		Cutoff value	≥10000	1.63 (0.66–4.05)	0.290	0.0	0.964	0.526
		Cutoff value		2.22 (1.16–4.24)	0.016	84.3	0.002	0.526
		Study quality	High	2.10 (1.62–2.74)		–	–	0.685
		Study quality	Low	2.00 (0.86–4.65)	0.109	76.9	0.005	0.685
LNI	OS	Countries	Eastern	2.49 (2.17–2.85)		71.4		0.007
		Countries	Western	2.90 (2.29–3.67)		60.5		0.007
		FIGO stage	I–II	2.97 (2.57–3.43)		65.8		0.001
			III–IV	–	–	–	–
			Both	2.04 (1.66–2.51)		72.3
		Study quality	High	2.52 (2.08–3.04)		68.5		0.639
		Study quality	Low	2.64 (2.26–3.09)		70.7		0.639
	EFS	Countries	Eastern	2.37 (2.03–2.77)		81.0		0.001
		Countries	Western	2.18 (1.75–2.72)		61.6		0.001
		FIGO stage	I–II	2.54 (2.14–3.01)		81.8		0.998
			III–IV	–	–	–	–
			Both	1.89 (1.57–2.26)		61.5
		Study quality	High	2.16 (1.73–2.70)		87.0
		Study quality	Low	2.40 (2.10–2.75)		51.3
LVSI	OS	Countries	Eastern	1.99 (1.64–2.43)		63.2		0.036
		Countries	Western	2.49 (1.72–3.60)		36.3	0.100	0.036
		FIGO stage	I–II	2.08 (1.70–2.55)		64.6		0.539
			III–IV	2.10 (0.32–13.68)	0.438	–	–
			Both	2.20 (1.66–2.90)		0.0	0.976
		Study quality	High	1.78 (1.41–2.24)		47.4	0.029	0.046
		Study quality	Low	2.30 (1.80–2.94)		62.0		0.046
	EFS	Countries	Eastern	1.87 (1.62–2.16)		48.0	0.001
		Countries	Western	1.80 (1.33–2.46)		80.5
		FIGO stage	I–II	1.92 (1.68–2.18)		51.1
			III–IV	0.94 (0.36–2.44)	0.899	–	–
			Both	1.02 (0.95–1.09)	0.572	–	–
		Study quality	High	1.77 (1.34–2.32)		85.6
		Study quality	Low	1.91 (1.63–2.23)		43.0	0.004
NLR	OS	Countries	Eastern	1.48 (1.23–1.79)		52.9	0.038	0.001
		Countries	Western	2.50 (1.39–4.50)	0.002	50.5	0.155	0.001
		FIGO stage	I–II	1.78 (1.37–2.31)		0.0	0.476	0.004
			III–IV	-	–	–	–
			Both	1.62 (1.22–2.14)	0.001	72.7	0.003
		Cutoff value	≥3.0	2.40 (1.75–3.28)		0.0	0.494
		Cutoff value		1.35 (1.15–1.59)		41.1	0.131
		Study quality	High	1.58 (1.23–2.03)		75.7	0.001	0.005
		Study quality	Low	2.04 (1.43–2.92)		0.0	0.926	0.005
	EFS	Countries	Eastern	1.56 (1.23–1.98)		76.6
		Countries	Western	3.58 (2.11–6.08)		–	–
		FIGO stage	I–II	1.99 (1.51–2.63)		0.0	0.816
			III–IV	-	–	–	–
			Both	1.61 (1.17–2.21)	0.003	86.1
		Cutoff value	≥3.0	2.12 (1.28–3.52)	0.004	58.4	0.065
		Cutoff value	< 3.0	1.51 (1.16–1.98)	0.002	81.7
		Study quality	High	1.65 (1.16–2.36)	0.006	85.8
		Study quality	Low	1.85 (1.24–2.78)	0.003	60.6	0.038
Parametrial invasion	OS	Countries	Eastern	2.16 (1.81–2.58)		31.7	0.060	0.828
		Countries	Western	2.26 (1.44–3.55)		67.5	0.001	0.828
		FIGO stage	I–II	2.15 (1.81–2.55)		31.4	0.053	0.024
			III–IV	1.11 (0.53–2.32)	0.782	–	–
			Both	2.26 (1.31–3.89)	0.003	68.9	0.007
		Study quality	High	1.90 (1.36–2.66)		66.1	0.001	0.050
		Study quality	Low	2.36 (1.96–2.64)		22.9	0.146	0.050
	EFS	Countries	Eastern	1.89 (1.63–2.21)		37.6	0.019	0.948
		Countries	Western	2.03 (1.66–2.21)		58.0	0.015	0.948
		FIGO stage	I–II	1.96 (1.68–2.28)		42.7	0.005	0.153
			III–IV	3.70 (1.14–11.96)	0.029	–	–
			Both	1.48 (1.01–2.15)	0.044	24.9	0.262
		Study quality	High	1.54 (1.32–1.80)		12.1	0.321
		Study quality	Low	2.23 (1.86–2.69)		32.7	0.056
PLR	OS	Countries	Eastern	2.20 (1.62–3.00)		0.0	0.531	0.101
		Countries	Western	1.54 (0.73–3.25)	0.260	69.8	0.069	0.101
		FIGO stage	I–II	2.10 (1.51–2.91)		0.0	0.486	0.342
			III–IV	–	–	–	–
			Both	1.86 (0.97–3.59)	0.062	65.6	0.055
		Cutoff value	≥150	2.59 (1.68–3.99)		0.0	0.862	0.081
		Cutoff value		1.72 (1.12–2.65)	0.014	48.4	0.121	0.081
		Study quality	High	1.55 (0.98–2.43)	0.059	45.1	0.162	0.033
		Study quality	Low	2.54 (1.76–3.66)		0.0	0.805	0.033
	EFS	Countries	Eastern	2.47 (1.80–3.38)		0.0	0.914	0.004
		Countries	Western	1.01 (0.60–1.70)	0.973	–	–	0.004
		FIGO stage	I–II	2.44 (1.71–3.48)		0.0	0.779	0.058
			III–IV	–	–	–	–
			Both	1.58 (0.63–3.95)	0.333	78.8	0.030
		Cutoff value	≥150	2.59 (1.58–4.23)		0.0	0.992	0.174
		Cutoff value		1.82 (0.96–3.46)	0.069	71.3	0.030	0.174
		Study quality	High	1.56 (0.62–3.93)	0.343	76.7	0.038	0.045
		Study quality	Low	2.44 (1.72–3.46)		0.0	0.779	0.045
Resection margin	OS	Countries	Eastern	1.88 (1.29–2.75)	0.001	65.7	0.002	0.268
		Countries	Western	2.22 (1.25–3.95)	0.006	44.1	0.111	0.268
		FIGO stage	I–II	1.89 (1.36–2.62)		57.3	0.004	0.050
			III–IV	1.55 (0.86–2.81)	0.148	–	–
			Both	5.49 (2.09–14.41)	0.001	–	–
		Study quality	High	2.13 (1.24–3.66)	0.006	74.6		0.569
		Study quality	Low	1.75 (1.27–2.40)	0.001	18.3	0.285	0.569
	EFS	Countries	Eastern	2.16 (1.56–2.99)		52.2	0.006	0.129
		Countries	Western	1.69 (1.20–2.37)	0.003	39.3	0.106	0.129
		FIGO stage	I–II	1.86 (1.43–2.43)		45.2	0.012	0.005
			III–IV	1.71 (1.20–2.43)	0.003	0.0	0.925
			Both	5.62 (2.78–11.37)		0.0	0.795
		Study quality	High	1.80 (1.33–2.45)		53.3	0.015	0.218
		Study quality	Low	2.26 (1.53–3.33)		45.7	0.032	0.218
SCC	OS	Countries	Eastern	1.72 (1.26–2.35)	0.001	42.0	0.078	0.884
		Countries	Western	1.50 (0.92–2.45)	0.105	–	–	0.884
		FIGO stage	I–II	1.81 (1.22–2.68)	0.003	0.0	0.737	0.259
			III–IV	1.00 (0.55–1.82)	0.992	–	–
			Both	1.97 (1.25–3.10)	0.003	63.1	0.028
		Cutoff value	≥10	1.39 (0.76–2.53)	0.288	20.4	0.285	0.654
		Cutoff value		1.77 (1.29–2.42)		45.4	0.076	0.654
		Study quality	High	2.61 (1.42–4.83)	0.002	37.0	0.204	0.019
		Study quality	Low	1.36 (1.15–1.60)		0.0	0.440	0.019
	EFS	Countries	Eastern	1.80 (1.33–2.45)		43.7	0.087	–
		Countries	Western	–	–	–	–	–
		FIGO stage	I–II	1.17 (0.61–2.22)	0.637	34.4	0.218	0.079
			III–IV	–	–	–	–
			Both	2.08 (1.51–2.87)		36.6	0.177
		Cutoff value	≥10	1.63 (0.56–4.76)	0.370	77.4	0.035	0.954
		Cutoff value		1.83 (1.33–2.53)		37.6	0.156	0.954
		Study quality	High	1.70 (1.14–2.56)	0.010	52.4	0.122	0.469
		Study quality	Low	1.86 (1.12–3.11)	0.017	48.2	0.102	0.469
Tumor grade	OS	Countries	Eastern	2.00 (1.37–2.93)		61.5	0.016	0.007
		Countries	Western	1.07 (0.78–1.45)	0.678	0.0	0.899	0.007
		FIGO stage	I–II	2.00 (1.37–2.93)		61.5	0.016	0.007
			III–IV	–	–	–	–
			Both	1.07 (0.78–1.45)	0.678	0.0	0.899
		Study quality	High	1.67 (0.90–3.10)	0.101	–	–	0.721
		Study quality	Low	1.76 (1.21–2.57)	0.003	69.4	0.002	0.721
	EFS	Countries	Eastern	1.39 (1.14–1.71)	0.001	39.2	0.130	0.480
		Countries	Western	1.16 (0.60–2.26)	0.661	11.6	0.288	0.480
		FIGO stage	I–II	1.41 (1.17–1.70)		30.3	0.186	0.226
			III–IV	–	–	–	–
			Both	0.89 (0.41–1.94)	0.769	–	–
		Study quality	High	1.35 (0.96–1.89)	0.084	54.1	0.113	0.754
		Study quality	Low	1.38 (1.05–1.82)	0.021	29.1	0.217	0.754
Tumor size	OS	Countries	Eastern	1.76 (1.52–2.05)		71.7		0.004
		Countries	Western	1.95 (1.51–2.53)		59.9	0.001	0.004
		FIGO stage	I–II	1.66 (1.41–1.97)		70.6
			III–IV	1.09 (0.55–2.15)	0.811	45.3	0.176
			Both	2.17 (1.78–2.65)		59.1
		Cutoff value	≥4.0 cm	1.72 (1.48–2.00)		69.6
		Cutoff value		2.09 (1.61–2.70)		64.8
		Study quality	High	1.87 (1.52–2.31)		66.1		0.010
		Study quality	Low	1.78 (1.51–2.11)		70.7		0.010
	EFS	Countries	Eastern	1.70 (1.46–1.98)		77.8
		Countries	Western	1.67 (1.25–2.22)	0.001	74.4
		FIGO stage	I–II	1.67 (1.45–1.93)		66.9
			III–IV	1.59 (0.89–2.83)	0.115	–	–
			Both	1.75 (1.34–2.28)		86.1
		Cutoff value	≥4.0 cm	1.66 (1.39–1.98)		78.5		0.062
		Cutoff value		1.76 (1.43–2.17)		77.1		0.062
		Study quality	High	1.48 (1.28–1.72)		68.3		0.053
		Study quality	Low	1.90 (1.54–2.35)		81.3		0.053

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Prognostic Significance of Clinicopathological Factors Influencing Overall Survival and Event-Free Survival of Patients with Cervical Cancer: A Systematic Review and Meta-Analysis

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