Importance of addition of HPV DNA testing to the cytology based cervical cancer screening and triage of findings with p16/Ki67 immunocytochemistry staining in 35 and 45 years old women LIBUSE trial data analysis.

OBJECTIVE

The study evaluates results of 2-years follow-up of patients in ages 35-36 and 45-46, who are participating in the project LIBUSE, that deals with efficacy of HPV DNA and Pap smear co-testing and p16/Ki67 dual staining in the Czech national cervical screening.

DESIGN

Prospective observational study.

SETTING

Department of Obstetrics and Gynecology, General University Hospital and 1st Medical Faculty, Charles University, Prague.

MATERIALS AND METHODS

Out of all women enrolled in the project LIBUSE only those who were at the beginning of the study 35-36 and 45-46 years old were sellected. Conventional Pap smear and HPV DNA test (Cobas 4800, Roche Diagnostics) had been collected at the baseline. Women were stratified according to their results in the three risk groups: 1. low-risk, 2. high-risk and 3. intermediate risk, who subsequently underwent p16/Ki67 dual staining. All high-risk patients and those with positive result of dual staing were refered to the expert colposcopy. The cases with biopsy proven precancers or cancers were considered as „positive findings“.

RESULTS

Altogether 352 women meet the age requirements. In 26 (7.6%) women had been proven HPV DNA positivity and out of the them 9 cases were HPV 16/18 positive. Severe cytological abnormality was found only in one patient (0.3%), who was simultaneously HPV positive. Ten women (2.8%) were classified as high-risk and directly refered to colposcopy. Another 18 patients underwent p16/Ki67 dual staining and 4 positive cases were refered to colposcopy too. After one year further 9 patients were classified as intermediate risk and 6 more were identified after two years of follow-up. Within two years 9 more patient were refered to colposcopy. After the entire period of follow-up in 10 patients biopsy confirmed precancer lesions, none of them had invasive cancer.

CONCLUSIONS

Addition of HPV DNA testing with selective HPV 16/18 genotyping to the cytology based screening significantly increases sensitivity and safety of our cervical screening program.