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Objective. This study aimed to investigate correlations between a panel of biomarkers/tumor markers and high-risk (HR) human papillomavirus (HPV)-positive versus HR-HPV-negative cervical lesions.

Materials and Methods. The study included 188 women who consecutively attended a colposcopy clinic because of PAP smears suggesting cervical intraepithelial neoplasia (CIN), and 40 women with normal vaginal cytology. Tissue microarray blocks were prepared from representative cervical cone or punch biopsies. Sections were stained for 12 biological markers, previously shown to be relevant in cervical neoplasms, and expression was correlated to the presence or absence of HR-HPV in cervical lesions.

Results. No correlations between expression of biomarkers and HPV status were found in normal epithelium. Expression of c-myc, CD4(+), Ki-67, and p16(INK4a) correlated significantly to HR-HPVYinfected epithelium compared with HR-HPV-negative epithelium. When adjustment was made for CIN grade, only the expression of Ki-67 correlated significantly with HPV status and CIN grade. Human papillomavirus status was stratified to normal epithelium, low-grade CIN, and high-grade CIN. Fragile histidine triad (FHIT), E-cadherin, Rb, Ki-67, and p16(INK4a) expression was significantly increased in HPV-positive tissue by increasing CIN grade. No correlation to tumor marker expression was observed in the HPV-negative tissue. Conclusions. This study described correlations, previously not investigated, between HPV status and tumor marker expression, that is, E-cadherin, Rb, and fragile histidine triad. Surprisingly, p16(INK4a) was not, although Ki-67 expression was, independently correlated to HPV positivity. The results of this study suggest that p16(INK4a) instead correlates independently with increasing CIN grade.

OBJECTIVE: The purpose of this study was to investigate correlations between smoking and serum cotinine, respectively, and tumor marker expression in cervical intraepithelial neoplasia (CIN) and normal epithelium. STUDY DESIGN: Women (n = 228) with cervical biopsy specimens that ranged histologically from normal to carcinoma in situ (CIN III) were included. Expression of 11 tumor markers with possible relevance in cervical neoplasms was studied. Smoking habits were recorded, and serum was assessed for cotinine concentrations. RESULTS: No differences were found in tumor marker expression in normal epithelium between smokers and nonsmokers. The tumor suppressors p53 and fragile histidine triad and the immunologic marker interleukin-10 were underexpressed, and the tumor markers cyclooxygenase-2 and Ki-67 were overexpressed in smoking, compared with nonsmoking, women with CIN and particularly in all fertile women. CONCLUSION: The molecular pattern indicates that smoking exerts unfavorable effects in cervical neoplasia. This provides biologic evidence of smoking being a true cofactor in cervical neoplasia.

Background: The study was conducted to investigate correlations between combined oral contraceptive (COC), any progestin-only contraceptive, medicated intrauterine device (MID) or systemic progestin-only (Syst-P) use and tumor marker expression in cervical intraepithelial neoplasia compared to nonusers.

Study Design: One-hundred ninety-five women of fertile age with cervical biopsies ranging histologically from normal epithelium to carcinoma in situ were recruited consecutively. Combined oral contraceptive, Syst-P and MID users were investigated according to the expression of 11 tumor markers.

Results: Overexpression of cyclooxygenase-2 (Cox-2) was observed in COC users, while interleukin 10 was underexpressed. When users of progestogen-only contraceptives were analyzed, there was a lower expression of cytokeratin 10 and interleukin 10. When only MID users were analyzed, a high expression of p53 was found. Expression of Cox-2, p53 and retinoblastoma protein differed between COC and MID users.

Conclusion: The study showed molecular alterations, which, in general, have not been studied previously in COC users and have never been studied in progestogen-only users. These biological events might be involved in epidemiological correlations found between hormonal contraceptive use and cervical neoplasms.

The aim of this study was to To investigate correlations between serum progesterone and serum estradiol levels and expression of tissue tumor markers in cervical intraepithelial neoplasia (CIN) and normal epithelium. Materials and Methods: Eighty women of fertile ages with cervical biopsies ranging histologically from normal to CIN III were included. Expression of eleven tumor markers was studied. Serum levels of progesterone and estradiol were analyzed. Exclusion criterion was hormonal contraceptive use. Results: In normal epithelium, low progesterone levels correlated to expression of epidermal growth factor receptor (EGFR) and CD4+. In initial analyses of CIN, high progesterone levels correlated with expression of retinoblastoma protein, p16 and cyclooxygenase-2 (COX-2), but after adjustment for CIN grade, only correlation to COX-2 expression remained significant. Expression of COX-2 and CD4+ correlated to serum estradiol levels in CIN. Conclusion: Serum levels of progesterone and estradiol appear to correlate with increased COX-2 expression in CIN. In addition, the study shows that evaluation of expression of tumor markers must take into account the grade of CIN.