1. 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”

2. 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.

3. Mechanism of p 16INK4a over-expression

4. 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.

5. 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.

6. 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).

7. 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.

8. 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.

9. HPV-L1 P 16 In 40 cases, analised for HPV-L1 expression, we observed the different localization in 1 case L1+/P16+ in HSIL.

10. HPV-L1 1 case L1+/P16+ in HSIL Cyto-histological HPV-L1 detection

11. P 16 P16 detection in basal layer

12. Cytologycal L1+/P16- in H-SIL P 16 HPV-L1

13. 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.