P09-04COMPARISSON OF P16/Ki67 DUAL IMMUNOCYTOCHEMICAL STAINING, HPV TESTING AND CYTOLOGY RESULTS OBTAINED IN THREE CYTOPATHOLOGY LABORATORIES PARTICIPATING IN SLOVENIAN CERVICAL CANCER SCREENING PROGRAM ZORA

09. HPV screening
V. Kloboves Prevodnik 1, U. Ivanus 2, N. Nolde 1, T. Jerman 2, A. Repse Fokter 3, S. Jezersek 1, Z. Pohar Marinsek 1, U. Klopcic 1, S. Hutter Celik 4, K. Gornik Kramberger 4, M. Primic Zakelj 2.
1Dept. of Cytopathology, Institute of Oncology Ljubljana, Zaloška 2, 1000 Ljubljana (Slovenia), 2Dept. of Epidemiology and Cancer Registry, Institute of Oncology Ljubljana, Zaloška 2, 1000 Ljubljana (Slovenia), 3Dept. of Pathology and Cytology, Celje General Hospital, Oblakova ulica 5, 3000 Celje (Slovenia), 4Dept. of Pathology,University Clinical Centre Maribor, Ljubljanjska ulica 5, 2000 Maribor (Slovenia)

Background / Objectives

Slovenian organized, population based cervical cancer screening program ZORA is cytology based. Women with low grade (LG) cytology are triaged with HPV testing. After the implementation of the program in the year 2003 the incidence of cervical cancer decreased for almost 50%, from 20.7 to 11.4 per 100.000 women (crude incidence rate). Despite the good results the gradual introduction of HPV primary screening is currently discussed in Slovenia and therefore the pilot study was conducted to compare the results of PAP test, p16/Ki67 dual imunocytochemical staining (ICS) and HPV testing within the Slovenian cervical cancer screening program.


Methods

In 129 women referred to colposcopy, cervical smears were obtained for cytological examination, p16/Ki67 dual ICS (CINtec PLUS test, Roche) and HPV testing (Hybrid Capture 2, Qiagen). Each PAP smear and ICS slide was evaluated blindly in 3 laboratories participating in Slovenian cervical cancer screening program by a screener and a cytopathologist in the same way as it is current practice in the program. Cytology was reported according to Bethesda classification and p16/Ki67 according manufacturer recommendations. Sensitivity and specificity for CIN2+ were calculated for LG cytology (ASCUS+), high grade (HG) cytology (HSIL+), p16/Ki67 dual ICS and HPV testing. For cytology and p16/Ki67 dual ICS summary estimates of sensitivity and specificity were calculated for the three laboratories participated in the study.


Results

The sensitivity for LG cytology, HG cytology, p16/Ki67 dual ICS and HPV testing were 69.2% (95% CI 54.1%−81.1%), 44.4% (95% CI 33.6%−55.8%), 88.2% (95% CI 82.7%−92.1%) and 96.8% (95% CI 89.0%−99.6%) respectively. The highest sensitivity was obtained for HPV testing, however the sensitivity for p16/KI67 dual ICS staining was much better than for cytology. The specificity for LG cytology, HG cytology, p16/Ki67 dual ICS and HPV testing were 67.2% (95% CI 56.4%−76.5%), 93.0% (95% CI 87.6%−96.1%), 73.1% (95% CI 66.5%−78.8%) and 59.1% (95% CI 46.3%−71.0%) respectively. The highest specificity was obtained for HG cytology and p16/Ki67 dual ICS. 


Conclusion

Our results were similar to the results of other studies and support the idea that the introduction of HPV primary screening with p16/Ki67 dual ICS or cytology triage could give better results than cytology primary screening with HPV triage. However, additional larger prospective study on the screening population must be carried out before the policy of cervical cancer screening program in Slovenia would be changed.


References