[Update on current care guidelines. Diagnosis, treatment and follow-up of cytological changes in the cervix, vagina and vulva]. / Kohdunkaulan, emättimen ja ulkosynnytinten solumuutokset--diagnostiikka, hoito ja seuranta.

Approximately 150 cervical cancer cases are diagnosed in Finland annually. Both incidence and mortality have decreased by 80% since organised screening began. Recently, screening based on primary HPV-testing with Pap-smear triage has been shown to be more sensitive and more specific among women over 35 years old in randomised studies and thus may be implemented in routine. Abnormal findings in Pap smears indicate management. Confirmed CIN1 lesions are followed up and CIN2 and worse lesions treated. Follow-up after treatment should be reliably arranged, because elevated risk of cancer remains over 20 years after treatment. Quality control is of utmost importance.

Combination of serum hCG beta and p53 tissue expression defines distinct subgroups of serous ovarian carcinoma.

Serous ovarian carcinoma comprises a clinically heterogenous group of tumors, and molecular markers stratifying patients into clinically meaningful subgroups are needed. Numerous markers have been evaluated, but none of them has yet been routinely incorporated into clinical practice. Previously we have found that elevated serum levels of the free beta subunit of human chorionic gonadotropin (hCG beta) and aberrant p53 expression confer poor prognosis in ovarian carcinoma. The aim of our study was to evaluate their combined effect in predicting the outcome of patients with serous ovarian carcinoma. The study material consisted of 173 consecutive patients treated for primary serous ovarian carcinoma in 1 institution between 1990 and 2000. The preoperative serum level of hCG beta was analyzed by a ultrasensitive and specific immunofluorometric assay, and p53 tumor tissue expression by immunohistochemistry using a novel classification. Elevated serum hCG beta (>or=2.0 pmol/L) was detected in 57 (33%) of 173 patients, and aberrant p53 expression in 103 (62%) of 167 interpretable cancers. Elevated hCG beta and aberrant p53 expression were strongly associated with poor prognosis (p < 0.0001 for both). Their additive prognostic effect was marked. Five-year survival was 14% (0-29%) when both markers were aberrant, 44% (29-60%) when either one was aberrant and 82% (70-94%) when both were normal. Preoperative serum hCG beta and tumor tissue p53 expression are feasible markers that divide serous ovarian carcinomas into clinically relevant subgroups.

HPV DNA testing as an adjunct in the management of patients with low grade cytological lesions in Finland.

BACKGROUND: Patients with recurrent low grade cytological abnormalities are at increased risk for high grade lesions. We wanted to see whether these patients could be identified by HPV DNA and pap tests. METHODS: A prospective study of 663 patients referred for a colposcopy on the basis of ASC-US or LSIL cytology. High-risk HPV DNA positivity and cytology were compared with histology. RESULTS: In total 65.6% samples were positive for HC2, and the overall proportion of CIN2+ lesions was 14.6%. No CIN2+lesions were found in patients testing HC2-, pap-. There were 5/97 (5.2%) high grade lesions, which were HC2-negative but pap-positive, including 1 cervical adenocarcinoma in situ. The corresponding histological sections were all positive for p16INK in immunostaining. In further analysis by PCR, 3 samples were positive for HPV DNA. High-risk HPV type 67, which is not included in the HC2 probe cocktail, was found in 1 case, and 2 cases were HPV positive but could not be typed. One CIN3 and one AIS remained HPV negative. In these 5 cases, the concomitant pap smear showed ASC-USx1, LSILx1, HSILx2 and AGCx1. During 6-month follow-up, a relatively high number of CIN2+(28/557, 5.0%) emerged from the non-CIN-CIN1 group. CONCLUSIONS: The HC2 test or pap test alone were not sensitive enough to detect all CIN2+lesions. A relatively high number of CIN2+cases emerged from the non-CIN-CIN1 group after 6 months. Adequate follow-up of patients with mild cytological abnormalities, including a repeat pap smear taken during colposcopy and control at 6 months is underscored. Combination of hrHPV DNA and pap test should be considered, since it had high negative predictive value.

Expression of trypsinogen-1, trypsinogen-2, and tumor-associated trypsin inhibitor in ovarian cancer: prognostic study on tissue and serum.

PURPOSE: The purpose is to study the prognostic significance of tissue expression of trypsinogen-1, trypsinogen-2, and tumor-associated trypsin inhibitor (TATI) and serum concentration of trypsinogen-2, trypsin-2-API (complex of trypsin-2 with alpha-1-proteinase inhibitor), and TATI in epithelial ovarian cancer. EXPERIMENTAL DESIGN: Expression of trypsinogen-1, trypsinogen-2, and TATI was determined by immunohistochemistry with monoclonal antibodies in tissue sections of tumors from 119 patients with untreated primary epithelial ovarian cancer. Preoperative serum concentrations of trypsinogen-2, trypsin-2-API and TATI were analyzed using specific immunoassays. RESULTS: Fifty-four percent of the tumors expressed trypsinogen-1, 45% expressed trypsinogen-2, and 30% expressed TATI. In patients with stage III and IV disease, TATI tissue expression (P = 0.002) and elevated TATI concentration in serum (P = 0.048) were associated with adverse cancer-specific and progression-free survival in univariate analysis. In multivariate analysis, TATI tissue expression (P = 0.005), tumor grade (P = 0.0001), histological type (P = 0.02), and stage (P = 0.0005) were independent prognostic factors for adverse cancer-specific survival and TATI tissue expression (P = 0.006) and grade (P = 0.0003) for progression-free survival. In multivariate analysis of all patients and those with advanced disease, serum trypsin-2-API concentration was an adverse prognostic factor for cancer-specific and progression-free survival, and it was independent of stage and histological type of the tumor (P