Hypoxic gene expression is a prognostic factor for disease free survival in a cohort of locally advanced squamous cell cancer of the uterine cervix

Figures & data

Figure 1. Gene expression levels of hypoxia induced genes (relative to reference genes) in cervical vs head and neck squamous cell carcinoma.

Table 1. Patient and treatment characteristics.

	All patients N = 183 (100%)		‘Less’ hypoxic N = 117 (64%)		‘More’ hypoxic N = 66 (36%)		p value
	N	%	N	%	N	%
Age
Median (range)	56	(22–90)	55	(22–90)	57	(27–81)	1.00
<55 years	89	49%	57	49%	32	48%
≥55 years	94	51%	60	51%	34	52%
FIGO2009 stage
IB-IIA	16	9%	8	7%	8	12%	0.012
IIB	117	64%	84	72%	33	50%
III-IVA	50	27%	25	21%	25	38%
T-score
Mean (95% CI)	7.2	(6.6–7.7)	6.7	(6.1–7.3)	8.0	(7.1–9.0)	0.011
0–4	41	22%	28	24%	13	20%
5–6	57	31%	44	38%	13	20%
7–9	43	23%	26	22%	17	26%
≥10	42	23%	19	16%	23	35%
N stage
N0	86	47%	55	47%	31	47%	0.20
N1: pelvic	73	40%	43	37%	30	45%
N2: para-aortic	24	13%	19	16%	5	8%
HPV-status
Negative	4	2%	3	3%	1	2%	0.90
Type 16/18	128	70%	80	68%	48	73%
Other types	51	28%	34	29%	17	26%
Para-aortic external RT
No	144	79%	91	78%	53	80%	0.85
Yes	39	21%	26	22%	13	20%
Chemotherapy
No	41	22%	24	21%	17	26%	0.46
Yes	142	78%	93	79%	49	74%

Figure 2. Local control, pelvic nodal control, extra pelvic control, and disease-free survival in 183 consecutive patients with locally advanced cervical cancer with squamous cell histology following state of the art chemoradiation and MRI guided brachytherapy.

Figure 3. Disease-free survival in patients with locally advanced cervical cancer with squamous cell histology stratified by hypoxia status using a validated 15-hypoxic gene expression classifier.

Table 2. Uni- and multivariate Cox analysis on disease-free survival.

	N	Univariate		Multivariate
		HR (95% CI)	p value	HR (95% CI)	p value
Hypoxia
’Less’ hypoxic	117	1.0 (reference)	0.035	1.0 (reference)	0.033
’More’ hypoxic	66	1.71 (1.04–2.82)		1.75 (1.04–2.92)
Age
<55 years	89	1.0 (reference)	0.030	1.0 (reference)	0.031
≥55 years	94	1.76 (1.06–2.94)		1.87 (1.06–3.32)
FIGO2009 stage
IB-IIA	16	1.0 (reference)	0.57	Not included
IIB	117	0.76 (0.30–1.96)
III-IVA	50	1.90 (0.73–4.95)	0.19
T-score
0–4	41	1.0 (reference)	0.59	Not included
5–6	57	1.25 (0.55–2.87)
7–9	43	1.77 (0.77–4.04)	0.18
≥10	42	3.40 (1.57–7.37)	0.0019
N stage
N0	86	1.0 (reference)	0.12	1.0 (reference)	0.017
N1: pelvic	73	1.54 (0.89–2.68)		2.03 (1.14–3.61)
N2: para-aortic	24	1.95 (0.95–3.99)	0.069	3.22 (1.48–7.03)	0.0032
HPV-16/18
No	55	1.0 (reference)	0.39	1.0 (reference)	0.92
Yes	128	0.79 (0.47–1.34)		0.97 (0.55–1.71)
Para-aortic external RT
No	144	1.0 (reference)	0.17	Not included
Yes	39	1.48 (0.85–2.59)
Chemotherapy
No	41	1.0 (reference)	0.0098	1.0 (reference)	0.042
Yes	142	0.49 (0.28-0.84)		0.54 (0.29-0.98)

Figure 4. Disease-free survival in patients with locally advanced cervical cancer with squamous cell histology stratified by T-score and hypoxia status using a validated 15-hypoxic gene expression classifier.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.