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E6 OF HPV-16 VARIANTS INDUCES
INVASIVE CAPACITY OF C-33A CELLS:
EZRIN AS REGULATOR OF THIS PROCESS
Rogríguez-Caneda J*, Martínez-Villalba D*, Illades-Aguiar B,
Del Moral-Hernández O, Zacapala-Gómez A E, Ortiz-Ortiz J,
Navarro-Tito N, Ortuño-Pineda C,
Mendoza-Catalán M A.
AUTONOMOUS UNIVERSITY
OF GUERRERO, MEXICO
CERVICAL CANCER
MORTALITY
The fourth cause of mortality in
woman.
CERVICAL CANCER
INCIDENCE
HUMAN PAPILLOMA VIRUS (HPV)
Margaret A. Stanley Clin. Microbiol. Rev. 2012;25:215-222
GENETIC VARIANTS OF HPV-16
27 E6 variants of HPV-16 was found.
- 7 new variants, not reported.
Ortiz-Ortiz et al, 2015. Virology Journal ,12:29
E6 VARIANTS OF HPV-16 MOST FREQUENTS
IN SOUTHERN MEXICO
27 E6 variants of HPV-16 was found.
- 7 new variants, not reported previously.
E6 Variant
AA-a
E-A176/G350
AA-c
E-G350
E-C188/G350
OR (CI 95%)
69,01 (7,6-628,9)
39.82 (4.1-386.0)
21.16 (2.6-172.6)
13.25 (2.0-87.1)
10.48 (1.4-78.9)
Ortiz-Ortiz et al, 2015. Virology Journal ,12:29
E6 ONCOPROTEIN OF HPV-16 VARIANTS
AFFECTS THE GENES EXPRESSION
Zacapala-Gómez, 2015.
Zacapala-Gómez, 2015.
EZRIN, A REGULATOR OF CELL MOTILITY
Ezrin is overexpressed in several cancer types
Clucas and Valderrama., 2014. Journal of Cell Science127, 267–275
EZRIN IS OVEREXPRESSED IN H-SIL AND CC
Rodriguez-Caneda, 2015.
EZRIN IS OVEREXPRESSED IN H-SIL AND CC
Cito-histologic Diagnosis
Ezrin
expression
level
Without SIL
HPV negative
% (n)
Without SIL
HPV positive
% (n)
L-SIL
% (n)
H-SIL
% (n)
CC
% (n)
65 (13)
33.33 (8)
45 (18)
25 (5)
0 (0)
Moderate
35 (7)
58.33 (14) 37.50 (15)
30 (6)
30 (6)
High
0 (0)
8.33 (2)
17.50 (7)
45 (9)
70 (14)
Total
20
24
40
20
20
Negative
or down
p value*
<0.001
*Chi-square test
Rodríguez-Caneda, 2015.
EZRIN EXPRESSION IS HIGHER IN SAMPLES
HPV-16 POSITIVES
Ezrin expression
% (n)
Low
% (n)
Moderate
% (n)
High
% (n)
Total
(n)
HPV-16
0.0 (0)
2.63 (1)
27.08 (13)
28.13 (9)
(23)
HPV-18
HPV-31/33
Others HPV-HR
25 (1)
2.63 (1)
4.17 (2)
6.25 (2)
(6)
0.0 (0)
7.89 (3)
8.33 (4)
25 (8)
(15)
25. (1)
34.21 (13)
27.08 (13)
31.25 (10)
(37)
HPV-LR
0.0 (0)
23.68 (9)
18.75 (9)
3.13 (1)
(19)
Negative
Total
50 (2)
28.95 (11)
14.58 (7)
6.25 (2)
(22)
4
38
48
32
(122)
Viral genotype
(39,45, 51,52,56,58,59)
Negative
p value*
0.005
*Chi-square test
Rodriguez-Caneda, 2015. In press
EZRIN IS LOCALIZED AT NUCLEUS
MAJORLY IN H-SIL AND CC CELLS
Rodriguez-Caneda, 2015.
E6 OF ASIATIC AMERICAN VARIANTS OF HPV16 INDUCES CELL MIGRATION
Mock
E6 Aaa-HPV 16
NSC-Ezr
CONCLUSIONS




The genetic variants E6 of HPV-16 are related
with cervical cancer developing.
E6 oncoprotein of genetic variants of HPV-16
modifies the genes transcription of C-33A cells.
Ezrin is overexpressed in H-SIL or CC samples.
Mainly in HPV-16 positive samples.
The variant AAa of HPV-16 induces migration of
cervical cells in an Ezrin-dependent manner.