L.I. Korolenkova

Intraepithelial (CIN3/CIS) and microinvasive cervical cancer is a widespread HPV-associated disease in young women. After conservative surgical procedures, the most popular of which is conization, it is extremely important to assess the treatment efficiency and follow-up the women properly because of the long-termed risk of persistent or recurrent disease. The latter may be revealed by positive HPV-testing. Study objective was to appraise the value of HPV Digene Hybride Capture 2 (HC2) testing in assessing conization efficiency, diagnosis of recurrent or persistent disease and predicting treatment outcome in patients with CIN3/CIS and microinvasive cervical cancer. Materials and methods: 416 patients with CIN3/CIS and microinvasive cervical cancer that underwent conization procedure were included in the study. HPV-testing (HPV typing by means of PCR and viral load assessment by HC2) before and 3 months after conization, cytological study and colposcopy were performed in all cases. Further follow-up in 6-12 month intervals included yearly HC2. Results: all 416 patients were HPV-positive preoperatively. After conization 93 % (387 patients) become HC2-negative and these women had no colposcopic or cytological signs of persistent or recurrent disease (follow-up time 10-62 months). Negative predictive value for persistent disease was 100 %. In 27 patients (7 %) HC2 remained positive although viral load has decreased. These patients also have no colposcopic or cytological signs of disease, but further follow-up showed growth of viral load in 19 patients: in 11 up to 100 RLU, in 8 up to 300-1500 RLU. In the first group there were dyskariosis and koilocytosis in smears, cervical curettage revealed CIN1 in five patients. In the second group 6-12 months after viral load growth cytological signs of disease were found out. Reconization was performed in five patients with HSIL and CIN 3 recurrence was confirmed, with no invasion. From three patients with LSIL or ASCUS CIN1-2 was diagnosed in two, one just had koilocytosis. It is evident that only patients with HC2 remaining positive after surgical procedure had persistent disease. Viral load growth predicted CIN persistence or recurrence earlier than cytological signs in pap smears. Meanwhile none of patients with positive HPV PCR had persistent disease by negative HC2. HC2 sensitivity and negative predictive value for persistent or recurrent disease was 100%. Positive predictive value and specificity were 44,8 % and 96 %, correspondently. Conclusion: Almost 100 % of CIN3/CIS and microinvasive cervical cancer are HPV-associated. After conization sensitivity of colposcopy and cytology get significantly lower making HC2 testing for HPV a single useful tool for predicting recurrent and persistent disease considering 100 % negative predictive value. Negative HC2 corresponds to absence of neoplastic epithelia after full excision of the involved part of transformation zone and may be seen as a sign of adequate excision and favorable outcome. Digene HC2 may be recommended for the assessment of treatment outcome and follow-up after conservative surgical procedures in patients with CIN3/CIS and microinvasive cervical cancer, as well as for choosing proper follow-up protocol. Progressive growth of HC2 values predicts CIN recurrence earlier than cytological changes.