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P16 Methylation Is an Early Event in Cervical Carcinogenesis
  1. Lee-Wen Huang, MD*,,,
  2. Hun-Shan Pan, MD*,,
  3. Yu-Hung Lin, MD*,,
  4. Kok-Min Seow, PhD*,,
  5. Heng-Ju Chen, MD*, and
  6. Jiann-Loung Hwang, MD*,
  1. *Department of Obstetrics and Gynecology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei;
  2. School of Medicine, Fu Jen Catholic University, Hsinchuang, Taipei Hsien; and
  3. School of Medicine, Taipei Medical University, Taipei, Taiwan.
  1. Address correspondence and reprint requests to Lee-Wen Huang, MD, Department of Obstetrics and Gynecology, Shin Kong Wu Ho-Su Memorial Hospital, No. 95 Wen Chang Rd, Shih-Lin District, Taipei 111, Taiwan. E-mail: m002057{at}


Background Aberrant gene promoter methylation is a critical event in tumorigenesis. The aim of this study was to explore the promoter hypermethylation of p16 and DAPK1 during the progression of cervical precancerous lesions.

Methods A series of 98 cervical neoplasms (72 cervical intraepithelial neoplasia and 26 cervical carcinomas) were evaluated. The promoter methylation status of p16 and DAPK1 was assessed from cervical scrapings by methylation-specific polymerase chain reaction.

Results For p16, the frequency of promoter hypermethylation showed an increasing trend from normal to dysplastic to invasive squamous cancer specimens, and this increase reached statistical significance (P < 0.0001). However, there was no significant difference in the promoter methylation state of DAPK1 with regard to the various grades of cervical lesions (P = 0.077). Specifically, methylation of p16 was a frequent event in the cervical carcinoma samples, and these figures were statistically significant compared with the normal and cervical intraepithelial neoplasia I cases (P = 0.015 and P = 0.021, respectively).

Conclusions These results imply that promoter hypermethylation of p16 occurs at an early stage of cervical neoplastic progression. This early event may play an initiating role in the malignant transformation of low-grade dysplasia into high-grade dysplasia and invasive carcinoma. We suggest that aberrant promoter methylation of p16 may serve as a useful biomarker during the follow-up of low-grade dysplasia.

  • Methylation
  • p16
  • Cervical intraepithelial neoplasia
  • Cervical carcinoma

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  • This study was supported by a research grant (SKH-8302-97-DR-20, SKH-8302-98-DR-23) from the Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.