title: Persistence of type-specific human papillomavirus infection and increased long-term risk of cervical cancer.
abstract: BACKGROUND
  Human papillomavirus (HPV) persistence is the pivotal event in cervical carcinogenesis. We followed a large-scale community-based cohort for 16 years to investigate the role of genotype-specific HPV persistence in predicting cervical cancer including invasive and in situ carcinoma.
  
  
  METHODS
  At the baseline examination in 1991-1992, 11,923 participants (aged 30-65 years) consented to HPV testing and cytology; 6923 participants were reexamined in 1993-1995. For HPV testing, we used a polymerase chain reaction-based assay that detected 39 HPV types. Women who developed cervical cancer were identified from cancer and death registries. Cumulative risks for developing cervical cancer among infected and persistently infected women were calculated by the Kaplan-Meier method.
  
  
  RESULTS
  Of 10,123 women who were initially cytologically normal, 68 developed cervical cancer. The 16-year cumulative risks of subsequent cervical cancer for women with HPV16, HPV58 (without HPV16), or other carcinogenic HPV types (without HPV16 or HPV58) were 13.5%, 10.3%, and 4.0%, respectively, compared with 0.26% for HPV-negative women. Women with type-specific persistence of any carcinogenic HPV had greatly increased risk compared with women who were HPV-negative at both visits (hazard ratio = 75.4, 95% confidence interval = 31.8 to 178.9). The cumulative cervical cancer risks following persistent carcinogenic HPV infections increased with age: The risks were 5.5%, 14.4%, and 18.1% for women aged 30-44 years, 45-54 years, and 55 years and older, respectively. However, newly acquired infections were associated with a low risk of cervical cancer regardless of age.
  
  
  CONCLUSIONS
  HPV negativity was associated with a very low long-term risk of cervical cancer. Persistent detection of HPV among cytologically normal women greatly increased risk. Thus, it is useful to perform repeated HPV testing following an initial positive test.
authors: Genomics Research Center, Academia Sinica, 128 Academia Rd Section 2, Nankang, Taipei 11529, Taiwan. cjchen@ntu.edu.tw
authors: Hui-Chi
authors: HC
authors: Chen
authors: Mark
authors: M
authors: Schiffman
authors: Ching-Yu
authors: CY
authors: Lin
authors: Mei-Hung
authors: MH
authors: Pan
authors: San-Lin
authors: SL
authors: You
authors: Li-Chung
authors: LC
authors: Chuang
authors: Chang-Yao
authors: CY
authors: Hsieh
authors: Kai-Li
authors: KL
authors: Liaw
authors: Ann W
authors: AW
authors: Hsing
authors: Chien-Jen
authors: CJ
authors: Chen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D052685:Alphapapillomavirus; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016017:Odds Ratio; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000453:epidemiology / Q000821:virology; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors; D014412:Tumor Virus Infections / Q000150:complications* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000821:virology*