p16INK4A expression and HPV-L1
detection in the uterine cervix:
cyto-histological and
immunoistochemical study
M.A. Caponio, T. Addati, G. Giannone, *G. Falco, A.
Labriola, S. Petroni, V. Rubini, G. Simone
UOC ANATOMIA PATOLOGICA *UOC GINECOLOGIA
IRCCS – Istituto Tumori “Giovanni Paolo II”
OBJECT:
The most important event in carcinogenesis of
the cervical cancer (CC) is the infection by HPV
and the viral integration in cellular DNA.
The “progression timing“ between the
developement of the lesion in CC after viral
integration is unknown.
P16INK4A protein is tightly correlated to
expression of HPV-L1 protein.
Mechanism of p16INK4a over-expression
METHODS
137 women underwent Pap Test using LBC.
78 cases had the corresponding bioptic/surgical
sample.
40 cases were analised for HPV-L1 protein
expression both in LBC and in the corresponding
tissue sample.
AIM
The prevalence of the lesions, the cyto-histological
correlation, the presence of HPV and the incidence
of p16 (score 0 to 4), were observed.
RESULTS (1)
In none of the 35 evaluated cases with Negative cytology,
(including 6 HPV+) and in 18 ASCUS, p16 immunoreactivity
(IR) has been evidenced. IR has been found in 1/4 cases
AGUS, in 4/20 L-SIL, in 6/11 H-SIL and in 2/4 SCC.
p16 score
N/0
1/2
3/4
25
8
-
n.
48
Cytology
NEGATIVE
n
35
n.e.
2
22
ASCUS
18
9
9
-
-
7
27
13
4
1
122
AGUS
L-SIL
H-SIL
SCC
ADENOCA
Total
4
24
12
4
1
98
5
2
41
3
11
3
2
36
1
4
6
2
1
14
4
1
7
RESULTS (2)
In 51/78 cases, in which the histological sample was
available, the p16 IR has been determined: a strong IR was
present in 1/28 negative cases, 2/8 lesions CIN1, 9/12 CIN2-3,
3/3 SCC. In the evaluable cases (excluding ASCUS, AGUS and
L-SIL) the Overall Agreement was 91% (83.3% with LSIL).
n.
41
8
5
15
7
2
78
Histology
NEGATIVE
CIN 1
CIN 2
CIN 3
SCC
ADENOCA
TOTAL
n
27
8
5
7
3
1
53
N/0
24
5
1
30
1/2
1
1
1
1
4
3/4
1
2
4
5
3
17
n.e.
1
1
2
RESULTS (3)
In 18 evaluable cases, p16 has been determined both on the
cytological and histological samples: in 2 cases* IR was
present only on the cytological sample, while in 1 case** the
opposite event was observed.
HISTO
CYTO
TOT.
P 16
0
1
2
3/4
N.V.
21
0
4
3
7
1
1**
1
2
1
1
3/4
2*
1
4
3
1
11
n.e.
1
1
RESULTS (4)
In 75 cases the presence of HPV has been determined: 15
case p16 IR positive also presented infection by LR-HR HPV;
in 21/44 cases that didn't express p16 IR, LR-HR HPV
infection was detected.
P16
HPV N
LR
HR
LR-HR
Total
0
23
4
7
10
44
1
1
1
2
2
1
4
3
10
3
2
7
2
11
4
4
2
6
n.e. Total
27
12
2
16
1
20
3
75
In 40 cases, analised for
HPV-L1 expression, we
observed the different
localization in 1 case
L1+/P16+ in HSIL.
HPV-L1
P 16
1 case L1+/P16+ in HSIL
Cyto-histological HPV-L1
detection
HPV-L1
HPV-L1
P 16
P16 detection in basal layer
P 16
Cytologycal L1+/P16- in H-SIL
HPV-L1
P 16
CONCLUSIONS:
Our study shows that the presence of p16
and HPV-L1 protein in cyto-histological
samples could be useful in giving
information on viral integration and
lesions progression.