Background
Results
HPV 16 E6 variants and phylogenetic analysis
Variants
|
HPV 16 E6 nucleotide position
|
Predicted amino acid change E6 protein (151 aa form)
|
Frequency
| ||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
109
|
110
|
131
|
132
|
143
|
145
|
176
|
182
|
183
|
185
|
188
|
189
|
256
|
257
|
271
|
286
|
289
|
306
|
310
|
335
|
350
|
403
|
424
|
442
|
532
|
535
|
N=330
|
%
| ||
HPV 16R | T | C | A | G | C | G | G | A | T | T | G | A | C | A | T | T | A | A | C | C | T | A | A | A | A | A | |||
Lineage EAS/Sublineage EUR | |||||||||||||||||||||||||||||
Class E-T350 |
51
|
15.45%
| |||||||||||||||||||||||||||
E-Prototype | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | No change | 43 | 13.03% |
E-G131 | - | - | G | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | R10G | 8 | 2.42% |
Class E-G350 |
220
|
66.67%
| |||||||||||||||||||||||||||
E-G350 | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | L83V | 132 | 40.00% |
E-C109/G350 | c | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | L83V | 6 | 1.82% |
E-G110/G350 | - | G | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | Q3E/L83V | 2 | 0.61% |
E-G131/G350 | - | - | G | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | R10G/L83V | 2 | 0.61% |
E-G131/C188/G350 | - | - | G | - | - | - | - | - | - | - | C | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | R10G/E29Q/L83V | 2 | 0.61% |
E-A176/G350 | - | - | - | - | - | - | A | - | - | - | - | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | D25N/L83V | 17 | 5.15% |
**E-A176/G424/G350 | - | - | - | - | - | - | A | - | - | - | - | - | - | - | - | - | - | - | - | - | G | - | g | - | - | - | D25N/L83V | 1 | 0.30% |
E-T182/G350 | - | - | - | - | - | - | - | T | - | - | - | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | I27L/L83V | 4 | 1.21% |
E-C182/G350 | - | - | - | - | - | - | - | C | - | - | - | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | I27L/L83V | 2 | 0.61% |
**E-C183/G350 | - | - | - | - | - | - | - | - |
C
| - | - | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | I27T/L83V | 3 | 0.91% |
E-G185/G350 | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | L28V/L83V | 2 | 0.61% |
E-A188/G350 | - | - | - | - | - | - | - | - | - | - | A | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | E29K/L83V | 1 | 0.30% |
E-C188/G350 | - | - | - | - | - | - | - | - | - | - | C | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | E29Q/L83V | 39 | 11.82% |
**E-C188/G310/G350 | - | - | - | - | - | - | - | - | - | - | C | - | - | - | - | - | - | - | G | - | G | - | - | - | - | - | E29Q/F69L/L83V | 2 | 0.61% |
**E-G189/T256/G350 | - | - | - | - | - | - | - | - | - | - | - | G | t | - | - | - | - | - | - | - | G | - | - | - | - | - | E29G/L83V | 1 | 0.30% |
E-G257/G350 | - | - | - | - | - | - | - | - | - | - | - | - | - | G | - | - | - | - | - | - | G | - | - | - | - | - | I52L/L83V | 1 | 0.30% |
**E-C306/G350 | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - |
C
| - | - | G | - | - | - | - | - | K68T/L83V | 1 | 0.30% |
E-C442/G350 | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | G | - | - | C | - | - | L83V/E113D | 1 | 0.30% |
**G535/G350 | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | G | - | - | - | - |
g
| L83V | 1 | 0.30% |
Lineage AA/NA/Sublineage AA1 | |||||||||||||||||||||||||||||
Class AA-a |
36
|
10.91%
| |||||||||||||||||||||||||||
AA-a | - | - | - | - | - | T | - | - | - | - | - | - | - | - | - | a | g | - | - | T | G | - | - | - | g | - | Q14H/H78Y/L83V | 35 | 10.61% |
**AA-a/C188 | - | - | - | - | - | T | - | - | - | - | C | - | - | - | - | a | g | - | - | T | G | - | - | - | g | - | Q14H/E29Q/H78Y/L83V | 1 | 0.30% |
Class AA-c |
22
|
6.67%
| |||||||||||||||||||||||||||
AA-c | - | - | - | - | - | T | - | - | G | - | - | - | - | - | - | a | g | - | - | T | G | - | - | - | g | - | Q14H/I27R/H78Y/L83V | 20 | 6.07% |
**AA-c/G185 | - | - | - | - | - | T | - | - | G | G | - | - | - | - | - | a | a | - | - | T | G | - | - | - | g | - | Q14H/I27R/L28V/H78Y/L83V | 1 | 0.30% |
AA-c/C271 | - | - | - | - | - | T | - | - | G | - | - | - | - | - | c | a | g | - | - | T | G | - | - | - | g | - | Q14H/I27R/H78Y/L83V | 1 | 0.30% |
Lineage AFR2/Sublineage Afr2a | |||||||||||||||||||||||||||||
Class Af2-a |
1
|
0.30%
| |||||||||||||||||||||||||||
Af2-a/C109/G403 | c | - | - | T | G | T | - | - | - | - | - | - | - | - | - | a | g | - | - | T | - | g | - | - | - | - | R10I/Q14D/H78Y | 1 | 0.30% |
HPV 16 E6 variants in cervical carcinoma and precursor lesions
Variant
|
Non-IL N=97
|
LSIL N=123
|
HSIL N=19
|
SCC N=76
|
ADC N=13
|
Other Epithelial Tumor N=2
|
Cervical carcinoma N=91
|
Total N=330
|
---|---|---|---|---|---|---|---|---|
E variants |
87 (89.69%)
|
108 (87.79%)
|
15 (78.94%)
|
53 (69.75%)
|
7 (53.84%)
|
1 (50.0%)
|
61 (67.05%)
|
271 (82.12%)
|
Class E-T350 |
23 (23.72%)
|
23 (18.7%)
|
1 (5.26%)
|
4 (5.26%)
|
-
|
-
|
4 (4.4%)
|
51 (15.45%)
|
E-Prototype | 17 (17.53%) | 23 (18.7%) | 1 (5.26%) | 2 (2.63%) | - | - | 2 (2.2%) | 43 (13.03%) |
E-G131 | 6 (6.19%) | - | - | 2 (2.63%) | - | - | 2 (2.2%) | 8 (2.42%) |
Class E-G350 |
64 (65.97%)
|
85 (69.09%)
|
14 (73.68%)
|
49 (64.49%)
|
7 (53.84%)
|
1 (50.0%)
|
57 (62.65%)
|
220 (66.67%)
|
E-G350 | 39 (40.21%) | 56 (45.53%) | 6 (31.58%) | 28 (36. 84%) | 3 (23.08%) | - | 31 (34.07%) | 132 (40.00%) |
E-C109/G350 | - | 3 (2.44%) | 1 (5.26%) | 2 (2.63%) | - | - | 2 (2.2%) | 6 (1.82%) |
E-G110/G350 | 1 (1.03%) | 1 (0.81%) | - | - | - | - | - | 2 (0.61%) |
E-G131/G350 | 1 (1.03%) | - | - | 1 (1.32%) | - | - | 1 (1.1%) | 2 (0.61%) |
E-G131/C188/G350 | 1 (1.03%) | 1 (0.81%) | - | - | - | - | - | 2 (0.61%) |
E-A176/G350 | 3 (3.09%) | 5 (4.07%) | 1 (5.26%) | 5 (6.58%) | 2 (15.38%) | 1 (50.0%) | 8 (8.79%) | 17 (5.15%) |
**E-A176/G424/G350 | - | - | - | 1 (1.32%) | - | - | 1 (1.1%) | 1 (0.30%) |
E-T182/G350 | - | 1 (0.81%) | 1 (5.26%) | 2 (2.63%) | - | - | 2 (2.2%) | 4 (1.21%) |
E-C182/G350 | 1 (1.03%) | 1 (0.81%) | - | - | - | - | - | 2 (0.61%) |
**E-C183/G350 | 3 (3.09%) | - | - | - | - | - | - | 3 (0.91%) |
E-G185/G350 | 1 (1.03%) | - | - | 1 (1.32%) | - | - | 1 (1.1%) | 2 (0.61%) |
E-A188/G350 | - | - | - | 1 (1.32%) | - | - | 1 (1.1%) | 1 (0.30%) |
E-C188/G350 | 11 (11.34%) | 13 (10.57%) | 5 (26.32%) | 8 (10.53%) | 2 (15.38%) | - | 10 (10.99%) | 39 (11.82%) |
**E-C188/G310/G350 | 1 (1.03%) | 1 (0.81%) | - | - | - | - | - | 2 (0.61%) |
**E-G189/T256/G350 | - | 1 (0.81%) | - | - | - | - | - | 1 (0.30%) |
E-G257/G350 | - | 1 (0.81%) | - | - | - | - | - | 1 (0.30%) |
**E-C306/G350 | 1 (1.03%) | - | - | - | - | - | - | 1 (0.30%) |
E-C442/G350 | 1 (1.03%) | - | - | - | - | - | - | 1 (0.30%) |
**G535/G350 | - | 1 (0.81%) | - | - | - | - | - | 1 (0.30%) |
AA variants |
10 (10.31%)
|
14 (11.38%)
|
4 (21.05%)
|
23 (30.27%)
|
6 (46.15%)
|
1 (50.0%)
|
30 (32.97%)
|
58 (17.58%)
|
Class AA-a |
4 (4.12%)
|
11 (8.94%)
|
3 (15.79%)
|
12 (15.79%)
|
5 (38.46%)
|
1 (50.0%)
|
18 (19.78%)
|
36 (10.91%)
|
AA-a | 3 (3.09%) | 11 (8.94%) | 3 (15.79%) | 12 (15.79%) | 5 (38.46 %) | 1 (50.0%) | 18 (19.78%) | 35 (10.61%) |
**AA-a/C188 | 1 (1.03%) | - | - | - | - | - | - | 1 (0.30%) |
Class AA-c |
6 (6.19%)
|
3 (2.44%)
|
1 (5.26%)
|
11 (14.48%)
|
1 (7.69%)
|
-
|
12 (13.19%)
|
22 (6.67%)
|
AA-c | 6 (6.19%) | 3 (2.44%) | 1 (5.26%) | 9 (11.84%) | 1 (7.69%) | - | 10 (10.99%) | 20 (6.07%) |
**AA-c/G185 | - | - | - | 1 (1.32%) | - | - | 1 (1.1%) | 1 (0.30%) |
AA-c/C271 | - | - | - | 1 (1.32%) | - | - | 1 (1.1%) | 1 (0.30%) |
Af variants |
-
|
1 (0.81%)
|
-
|
-
|
-
|
-
|
-
|
1 (0.30%)
|
Class Af2-a |
-
|
1 (0.81%)
|
-
|
-
|
-
|
-
| - |
1 (0.30%)
|
Af2-a/C109/G403 | - | 1 (0.81%) | - | - | - | - | - | 1 (0.30%) |
Variants
|
Non-IL N (%)
|
LSIL N (%)
|
OR (CI 95%) P
|
HSIL N (%)
|
OR (CI 95%) P
|
SCC N (%)
|
OR (CI 95%) p
|
ADC N (%)
|
OR (CI 95%) P
|
Other epithelial tumor N (%)
|
Cervical carcinoma N (%)
|
OR (CI 95%) P
|
---|---|---|---|---|---|---|---|---|---|---|---|---|
Class E-T350a
|
23 (23.71%)
|
23 (18.7%)
|
-
|
1 (5.26%)
|
-
|
4 (5.26%)
|
-
|
0 (0%)
b
|
-
|
0 (0.0%)
|
4 (4.40%)
|
-
|
E-Prototype | 17 (17.53%) | 23 (18.7%) | 1* | 1 (5.26%) | 1* | 2 (2.63%) | 1* | 0 (0%)b
| 1* | - | 2 (2.2%) | 1* |
Class E-G350 |
64 (65.98%)
|
85 (69.11%)
|
0.97
|
3.73
|
12.66
|
2.42
|
14.12
| |||||
0.47-1.99
|
14 (73.68%)
|
0.46-30.44
|
49 (64.47%)
|
1.89-84.92
|
7 (53.85%)
|
0.25-∞ |
1 (50.0%)
|
57 (62.65%)
|
2.19-90.97
| |||
0.94
|
0.22
|
0.009
|
0.44
|
0.005
| ||||||||
E-G350 | 39 (40.21%) | 56 (45.53%) | 1.01 | 2.58 | 12.56 | 1.74 | 13.25 | |||||
0.47-2.17 | 6 (31.58%) | 0.29-23.17 | 28 (36.84%) | 1.84-85.86 | 3 (23.08%) | 0.15-∞ | - | 31 (34.07%) | 2.02-87.12 | |||
0.98 | 0.39 | 0.010 | 0.65 | 0.007 | ||||||||
E-A176/G350 | 3 (3.09%) | 5 (4.07%) | 1.49 | 5.82 | 24.79 | 12.62 | 39.82 | |||||
0.31-7.23 | 1 (5.26%) | 0.28-121.37 | 5 (6.58%) | 2.33-263.35 | 2 (15.38%) | 0.79-∞ | 1 (50.0%) | 8 (8.79%) | 4.11-386.04 | |||
0.62 | 0.26 | 0.008 | 0.07 | 0.001 | ||||||||
E-C188/G350 | 11 (11.34%) | 13 (10.57%) | 1.0 | 7.91 | 8.56 | 3.05 | 10.48 | |||||
0.35-2.84 | 5 (26.32%) | 0.81-77.58 | 8 (10.53%) | 1.07-68.26 | 2 (15.38%) | 0.23-∞ | - | 10 (10.99%) | 1.39-78.92 | |||
0.99 | 0.08 | 0.043 | 0.40 | 0.023 | ||||||||
Class AA-a |
4 (4.12%)
|
11 (8.94%)
|
2.18
|
12.65
|
35.21
|
21.24
|
54.51
| |||||
0.58-8.17
|
3 (15.79%)
|
1.02-156.20
|
12 (15.79%)
|
3.87-320.39
|
5 (38.46%)
|
1.75-∞ |
1 (50.0%)
|
18 (19.78%)
|
6.36-467.62
| |||
0.25
|
0.048
|
0.002
|
0.016
|
0.000
| ||||||||
AA-a | 3 (3.09%) | 11 (8.94%) | 3.08 | 17.40 | 43.73 | 26.69 | 69.01 | |||||
0.73-13.04 | 3 (15.79%) | 1.32-229.60 | 12 (15.79%) | 4.55-420.56 | 5 (38.46%) | 2.10-∞ | 1 (50.0%) | 18 (19.78%) | 7.57-628.96 | |||
0.13 | 0.03 | 0.001 | 0.01 | 0.000 | ||||||||
Class AA-c |
6 (6.19%)
|
3 (2.44%)
|
0.44
|
2.79
|
24.46
|
3.01
|
25.28
| |||||
0.10-2.06
|
1 (5.26%)
|
0.15-52.20
|
11 (14.47%)
|
2.89-207.12
|
1 (7.69%)
|
0.15-∞ |
-
|
12 (13.19%)
|
3.12-204.74
| |||
0.30
|
0.49
|
0.003
|
0.47
|
0.002
| ||||||||
AA-c | 6 (6.19%) | 3 (2.44%) | 0.46 | 2.93 | 19.97 | 2.99 | 21.16 | |||||
0.10-2.15 | 1 (5.26%) | 0.16-54.90 | 9 (11.84%) | 2.34-170.25 | 1 (7.69%) | 0.15-∞ | - | 10 (10.99%) | 2.59-172.56 | |||
0.32 | 0.47 | 0.006 | 0.47 | 0.004 | ||||||||
Class Af2-a |
0 (0%)
|
1 (0.81%)
|
-
|
0 (0%)
|
-
|
0 (0%)
|
-
|
0 (0%)
|
-
|
0 (0%)
|
0 (0%)
|
-
|
Patient
|
HPV 16 E6 Novel variant
|
Accession number GenBank
|
Nucleotide change
|
Amino acid change (not previously reported)
|
Women residence (City/State region)
|
Diagnosis/Sampling year
|
Follow up Diagnosis/Year
|
---|---|---|---|---|---|---|---|
1 | E-A176/G424/G350 | KJ465994 | G424 | - | Atoyac/Coast | Cervical carcinoma 2003 | - |
2 | E-C183/G350 | KJ465995 | C183 | I27T | Chilpancingo/Center | Non-IL 2002 | LSIL 2006 |
3 | E-C183/G350 | KJ465995 | C183 | I27T | Chilpancingo/Center | Non-IL 2006 | LSIL 2009 |
4 | E-C183/G350 | KJ465995 | C183 | I27T | Chilpancingo/Center | Non-IL 2002 | - |
5 | E-C188/G310/G350 | KJ465996 | G310 | - | Chilpancingo/Center | Non-IL 2004 | Non-IL 2005 |
6 | E-C188/G310/G350 | KJ465996 | G310 | - | Chilpancingo/Center | LSIL 2009 | LSIL 2012 |
7 | E-G189/T256/G350 | KJ465998 | G189 and T256 | - | Chilpancingo/Center | LSIL 2008 | LSIL 2009 |
8 | E-C306/G350 | KJ465997 | C306 | K68T | Acapulco Coast | Non-IL 2003 | - |
9 | E-G535/G350 | KJ465999 | G535 | - | Tepecoacuilco/North | LSIL 2006 | - |
10 | AA-a/C188 | KJ465992 | C188 | - | Iguala/North | Non-IL 1997 | - |
11 | AA-c/G185 | KJ465993 | G185 | - | Juchitan/North | Cervical carcinoma 1998 | - |
Sequence Data
Discussion
Region of Mexico
|
State/City
|
Genome region
|
Samples
|
Histology
|
HPV 16 E
|
HPV 16 E-Prototype
|
HPV 16 E-G350
|
AA
|
AA-a
|
AA-c
|
Reference
|
---|---|---|---|---|---|---|---|---|---|---|---|
Central | Mexico City | E6, L1 | 80 | SCC | 56% | 4% | 52% | 44% | - | - | Berumen, et al., 2001 |
6 | ADC | 0% | 0% | 0% | 100% | - | - | ||||
20 | Non-IL | 90% | 5% | 85% | 10% | - | - | ||||
Central | Mexico City | E6 | 50 | SCC | 30% | - | - | 40% | 32% | 8% | Lizano, et al., 2006 |
11 | ADC | 55% | - | - | 45% | 27% | 18% | ||||
23 | HSIL | 74% | - | - | 26% | 26% | 0% | ||||
13 | LSIL | 54% | - | - | 46% | 46% | 0% | ||||
16 | Non-IL | 56% | - | - | 44% | 44% | 0% | ||||
North-Central | San Luis Potosí | E6 | 2 | ICC | 100% | 50% | 50% | 0% | 0% | 0% | López-Revilla, et al., 2009 |
9 | HSIL | 89% | 33% | 56% | 11% | 11% | 0% | ||||
27 | LSIL | 96% | 85% | 11% | 4% | 4% | 0% | ||||
Northeastern | Nuevo León | LCR | 112 | Undefined | 13% | - | - | 87% | - | - | Calleja-Macias, et al., 2004 |
Southeastern | Yucatan | E6 | 25 | IIC | 52% | 28% | 24% | 44% | - | - | González-Losa, et al. 2004 |
15 | LSIL | 100% | 66% | 33% | 0% | 0% | 0% | ||||
Southern | Guerrero | E6 | 45 | ICC | 67% | - | - | 33% | - | - | Illades-Aguiar, et al., 2010 |
10 | HSIL | 90% | - | - | 10% | - | - | ||||
18 | LSIL | 67% | - | - | 33% | - | - | ||||
5 | Non-IL | 60% | - | - | 40% | - | - | ||||
Southern | Guerrero | E6 | 76 | SCC | 70% | 3% | 64% | 30% | 16% | 14% | |
13 | ADC | 54% | - | 54% | 46% | 38% | 8% | ||||
19 | HSIL | 79% | 5% | 74% | 21% | 16% | 5% | Present study | |||
123 | LSIL | 88% | 19% | 69% | 11% | 9% | 2% | ||||
97 | Non-IL | 90% | 18% | 66% | 10% | 4% | 6% |