Abstract: Background and purpose: Cervical cancer is the most common gynecological malignancy, and human papillomavirus (HPV) is closely related to cervical cancer/precancerous lesions. Correlation between expressions of HPV16 E7 and FoxM1 was found in cervical tissue biopsy RNA samples and cervical cancer cell lines. This study aimed to discover the potential immunohistochemical markers for cervical squamous cell carcinoma (SCC) and its precursor. We conducted correlation analysis for high-risk HPV (hrHPV) infection versus nuclear protein expressions of transcriptional factor FoxM1 and its downstream target Cdc25B using uterine cervical tissues. Methods: Histological samples obtained from cervical biopsy, conization or hysterectomy were collected from pathology archives of Fudan University Shanghai Cancer Center from 2007 to 2009. Nuclear expressions of FoxM1 and Cdc25B were evaluated by immunohistochemistry and compared with P16 and Ki-67 immunostaining, as well as HPV DNA tests for 23 genotypes. Results: A total of 140 cases were recruited, including normal (n=22), cervical intraepithelial neoplasia (CIN)1 (n=28), CIN2/3 (n=50) and SCC (n=40) specimens. The positive rates of hrHPV, FoxM1, Cdc25B, P16 and Ki-67 in CIN2+ were 100.00% (90/90), 100.00% (90/90), 94.44% (85/90), 85.56% (77/90) and 97.78% (88/90) respectively, and all rates increased with the severity of the disease (Jonckheere-Terpstra test, P<0.0001). FoxM1 and Cdc25B expressions correlated with hrHPV infection, P16 and Ki-67 (Spearman’s correlation test, P<0.0001). The area under the curve (AUC) values of FoxM1 and Cdc25B for diagnosing CIN2+ were 0.850 and 0.822, respectively. Conclusion: The correlation between hrHPV infection and FoxM1 or Cdc25B protein expression in cervical squamous epithelium was confirmed. Nuclear FoxM1 and Cdc25B proteins may be potential biomarkers for CIN2+.

Key words: Uterine cervix, Human papillomavirus, FoxM1, Cdc25B