Cigarette smoke stimulates VEGF-C expression in cervical intraepithelial neoplasia (CIN) 1 and 2 lesions

Morihiko Inamine, Yutaka Nagai, Akira Mitsuhashi, Satoru Nagase, Nobuo Yaegashi, Hiroyuki Yoshikawa, Yoichi Aoki

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Objective: Vascular endothelial growth factors (VEGFs) are involved in angiogenesis, but molecular links to the most important etiological agents, human papillomavirus (HPV) and smoking, need to be clarified. Methods: Archival samples at the first diagnosis of 64 cervical intraepithelial neoplasia grade 1 or 2 (CIN 1/2) lesions were examined immunohistochemically using anti-VEGF-C and anti-Ki-67 antibodies. HPV types were identified from cervical samples by restriction fragment length polymorphism, which has been shown to identify at least 26 types of genital HPVs. Follow-up data were available for all patients with CIN lesions. Results: Cervical intraepithelial neoplasia lesions regressed in 47 cases and were persistent in 17 cases. Twenty-two smokers, 8 former smokers, and 34 non-smokers were enrolled in the study. The median observation period was 52.3 months. Significantly higher VEGF-C expression was observed in 8 smokers with persistent CIN persistence (49.0 ± 16.6%, P < 0.01), whereas no significant difference was observed in Ki-67 expression. The median time to regression was significantly longer in the 10 smokers with high VEGF-C expression (48.3 months, P = 0.030) than that in the others. HPV was detected in 56 of the 64 cases. Thirty-two patients had high-risk HPV, 13 had intermediate-risk HPV, and 2 had low-risk HPV. No significant difference was observed among the HPV risk groups in both average Ki-67 and VEGF-C expression. Conclusions: These findings suggest that VEGF-C may play an important role in cigarette smoking-associated cervical carcinogenesis.

Original languageEnglish
Pages (from-to)498-504
Number of pages7
JournalInternational Journal of Clinical Oncology
Issue number5
Publication statusPublished - 2012 Oct


  • CIN 1/2
  • Cigarette smoke
  • HPV
  • VEGF-C

ASJC Scopus subject areas

  • Surgery
  • Hematology
  • Oncology


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