Background
Methods
Study population
Analysis of HPV16 E6 and LCR by PCR-sequencing
Data analysis
Results
HPV 16-posotive women (%) n=304 | |
---|---|
Age (years)
| |
Mean ± SD | 48.9 ± 11.7 |
Median | 46 |
Smoking (no. of women)
| |
Never | 121 (39.8) |
Ever | 124 (40.8) |
Unknown | 59 (19.4) |
Cervical disease (no. of women)
| |
Normal | 95 (31.3) |
LSIL | 10 (3.3) |
CIN1 | 32 (10.5) |
CIN2,3 | 117 (38.5) |
Cancer | 50 (16.4) |
Persistence (no. of women)
| |
Persistence | 168 (55.3) |
Transient | 106 (34.9) |
Undefined | 30 (9.9) |
Persistence in HPV 16 European T350G (no. of women)
| |
Persistence | 16 (9.5) |
Transient | 12 (11.3) |
Undefined | 2 (6.6) |
Persistence in As lineage (no. of women)
| |
Persistence | 81 (48.2) |
Transient | 22 (20.6) |
Undefined | 10 (33.3) |
Genomic polymorphisms of HPV16 E6 and LCR
Variation of HPV-16 E6 at nucleotide position (450bp) | Grade of Related Cervical lesion | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Categories | 94 | 131 | 176 | 178 | 215 | 241 | 335 | 350 | 442 | Normal n =95 | CIN1/LSIL n =42 | CIN2-3 n =117 | CC n =50 | Total n=304 |
KO2718 | G | A | G | T | C | T | C | T | A | |||||
Variation | A | C/G | A | A/G | T | G | T | G | C | |||||
EUR | _ | _ | _ | _ | _ | _ | _ | _ | _ | 10 | 5 | 4 | 5 | 24 |
EUR | a | _ | _ | _ | _ | _ | _ | _ | _ | 10 | 2 | 18 | 0 | 30 |
EUR | _ | _ | _ | _ | t | _ | _ | _ | _ | 10 | 2 | 0 | 0 | 12 |
EUR | _ | _ | _ | _ | _ | g | _ | _ | _ | 6 | 10 | 2 | 4 | 22 |
EUR | _ | _ | a | _ | _ | _ | _ | _ | _ | 12 | 4 | 1 | 0 | 17 |
EUR | _ | _ | _ | _ | _ | _ | _ | _ | C | 5 | 0 | 0 | 0 | 5 |
EUR | _ | _ | _ | _ | _ | _ | T | _ | _ | 11 | 2 | 0 | 0 | 13 |
EUR | _ | _ | _ | A | _ | _ | _ | _ | _ | 7 | 4 | 17 | 10 | 38 |
EUR | a | _ | _ | _ | _ | _ | _ | G | _ | 4 | 0 | 0 | 0 | 4 |
EUR | a | _ | _ | _ | _ | _ | _ | G | C | 3 | 0 | 0 | 0 | 3 |
EUR | _ | G | _ | _ | _ | _ | _ | G | _ | 0 | 1 | 8 | 0 | 9 |
EUR | _ | _ | _ | _ | _ | _ | _ | G | _ | 3 | 2 | 9 | 0 | 14 |
As | _ | c | _ | G | _ | _ | _ | _ | _ | 6 | 3 | 4 | 19 | 32 |
As | _ | _ | _ | G | _ | _ | _ | _ | _ | 8 | 7 | 54 | 12 | 81 |
AminoAcid substitution | _ | R10G | _ | D25E | _ | _ | H78Y | L83V | E113D |
Nucleotide variations | Transcription factors | No. of women with cervical different grades of cervical lesions dysplasia | ||||
---|---|---|---|---|---|---|
Normal n=95 | CIN1/LSIL n=42 | CIN2–3 n=117 | CC n=50 | Total n=304 | ||
N
G7193T
|
SRY
|
95
|
42
|
117
|
50
|
304
|
T7201C
|
SRY
|
65
|
8
|
17
|
16
|
106
|
T7228A
|
CdxA
|
17
|
4
|
0
|
8
|
29
|
A7238C
|
CdxA
|
25
|
4
|
8
|
0
|
37
|
T7238A
|
RAP1
|
17
|
4
|
0
|
8
|
29
|
C7270T
|
USF
|
65
|
8
|
17
|
16
|
106
|
A7279T
|
USF
|
0
|
5
|
8
|
4
|
17
|
A7287C
|
65
|
8
|
17
|
16
|
106
| |
A7289C
|
51
|
8
|
13
|
8
|
80
| |
N
C7294T
|
CdxA
|
0
|
4
|
8
|
10
|
22
|
N
G7319A
|
0
|
4
|
8
|
10
|
22
| |
N
A7326G
|
0
|
4
|
8
|
10
|
22
| |
A7339T
|
SRY
|
12
|
4
|
0
|
8
|
24
|
N
T7350A
|
Dfd, S8
|
0
|
4
|
8
|
10
|
22
|
N
T7368G
|
CF2-II
|
0
|
4
|
8
|
10
|
22
|
N
7434C(Ins)
|
95
|
42
|
117
|
50
|
304
| |
C7436T
|
E2
|
95
|
42
|
117
|
50
|
304
|
G7447T
|
12
|
4
|
0
|
8
|
24
| |
G7456A
|
12
|
4
|
0
|
8
|
24
| |
G7502T
|
CdxA
|
17
|
4
|
4
|
8
|
33
|
N
T7503G
|
HSF
|
0
|
4
|
8
|
10
|
22
|
N
A7515C
|
AP-1,cap
|
0
|
4
|
8
|
10
|
22
|
G7521A
|
95
|
42
|
117
|
50
|
304
| |
N
G7553T
|
Sox-5, SRY,HFH-2
|
0
|
4
|
8
|
10
|
22
|
N
A7602G
|
P
|
0
|
4
|
8
|
10
|
22
|
T7608C
|
Hb
|
8
|
0
|
4
|
4
|
16
|
G7677A
|
E2F
|
12
|
4
|
0
|
8
|
24
|
G7683A
|
E2F
|
12
|
4
|
0
|
8
|
24
|
T7714G
|
19
|
7
|
2
|
2
|
30
| |
A7730C
|
Oct-1
|
65
|
8
|
17
|
16
|
106
|
N
A7740T
|
Oct-1
|
0
|
4
|
8
|
10
|
22
|
T7755A
|
12
|
4
|
0
|
8
|
24
| |
T7781C
|
cap
|
25
|
0
|
17
|
0
|
42
|
T7841A
|
12
|
4
|
0
|
0
|
16
| |
G7842A
|
65
|
8
|
17
|
16
|
106
| |
N
7863A(Del)
|
95
|
42
|
117
|
50
|
304
| |
G7868A
|
28
|
0
|
9
|
4
|
34
| |
T7880C
|
CdxA
|
12
|
4
|
0
|
8
|
24
|
A7884C
|
12
|
4
|
0
|
8
|
24
| |
G7885A
|
12
|
4
|
0
|
8
|
24
| |
C7930T
|
SRY
|
65
|
8
|
17
|
16
|
106
|
Association of HPV16 polymorphisms with persistent infection
Association of HPV16 polymorphisms with risk for developing CIN2,3
No. of isolates with disease grade (%) n=304 | ||||
---|---|---|---|---|
Variable | <CIN2,3 (n = 137) | ≥ CIN2,3 (n =167) | Crude OR (95% CI)* | Adjusted OR (95% CI) * |
Number of HPV types per sample
| ||||
No. of types (median)
| 2 | 3 | 1.1 (0.9–1.4) | nd |
EUR lineage
|
113(82.5)
|
78(46.7)
|
5.0 (2.9-8.3)
|
5.8(3.2-9.4)
|
E-350G/T | 13(11.5) | 17(21.8) | 0.5(0.2-1.0) | nd |
E-94G/A | 17(15.0) | 18(23.1) | 0.6(0.3-1.2) | nd |
As lineage
|
24(17.5)
|
89(53.3)
|
0.2 (0.1-0.3)
|
0.3(0.2-0.8)
|
As-131A/C | 9(37.5) | 23(25.9) | 1.4(0.4-3.4) | nd |
E6 variations
| ||||
Referent variants | 84 (61.3) | 88 (52.6) | 1.0(reference) | 1.0(reference) |
R10G/ L83V | 1(0.7) | 8(4.8) | 0.1(0.0-1.0) | 0.1(0.1-0.9) |
LCR variations
| ||||
Referent variants | 137 (100) | 167 (100) | 1.0(reference) | 1.0(reference) |
Co-variation of C7294Ta
| 4 (1.5) | 18 (10.8) | 0.2 (0.1-0.6) | 5.7(0.1-0.7) |